Ciprofloxacin-Resistant Salmonella enterica Serotype Typhimurium, China
EID -Volume 14, Number 3–March 2008
Ciprofloxacin-Resistant Salmonella enterica Serotype Typhimurium, China
Shenghui Cui,* Jingyun Li,* Ziyong Sun,† Changqin Hu,* Shaohong Jin,* Yunchang Guo,‡ Lu Ran,‡ and Yue Ma* *State Food and Drug Administration, Beijing, People's Republic of China; †Huazhong University of Science and Technology, Wuhan, People's Republic of China; and ‡Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China
Salmonellae are a common cause of community-acquired foodborne bacterial gastroenteritis worldwide. The incidence of Salmonella infections in the People's Republic of China has not been well documented. However, in the United States, ≈1.4 million persons are infected by Salmonella spp. each year (1). Although >2,500 serotypes have been reported, Salmonella enterica serotype Typhimurium is 1 of the leading serotypes causing salmonellosis worldwide (2). Fluoroquinolones such as ciprofloxacin are strongly recommended for treatment of severe S. Typhimurium infections in adults (3).
In this study, we characterized all S. Typhimurium isolates recovered from May 2002 through October 2005 from outpatients of Tongji Hospital, Wuhan, China, a sentinel hospital in the National Center for Surveillance of Antimicrobial Resistance. During the time of this study, Tongji Hospital strictly followed the recommendation for treatment of severe S. Typhimurium infections.
The Study
We analyzed stool samples from outpatients who came to Tongji Hospital from the local community for treatment of diarrhea during the study period. A total of 44 S. Typhimurium isolates were recovered from the samples. S. Typhimurium was identified by using standard biochemical tests and commercial typing antiserum (Statens Serum Institute, Copenhagen, Denmark) according to the manufacturer's instructions. MICs of 15 antimicrobial drugs (Table) were determined by using the broth-microdilution method; susceptibility to streptomycin was measured by using the disk-diffusion method as recommended by the Clinical and Laboratory Standards Institute (4). All isolates were further characterized by mutation analysis in the quinolone-resistance determining regions (QRDRs), pulsed-field gel electrophoresis (PFGE), and screening for class I integrons and β-lactamase genes as previously described (5–8).
Of the 44 isolates, 36 (82%) were resistant to nalidixic acid and 31 (70%) were resistant to ciprofloxacin (Table). Only 3 isolates, recovered in 2002, were susceptible to all 15 tested antimicrobial drugs; 36 (82%) displayed resistance to at least 8 drugs. Of 13 antimicrobial drug–resistant phenotypes identified, the most often observed phenotype (21/44) was resistance to amoxicillin–clavulanic acid, ampicillin, chloramphenicol, ciprofloxacin, gentamicin, nalidixic acid, sulfamethoxazole, streptomycin, trimethoprim–sulfamethoxazole, and tetracycline (R-type AcAmCCpGNSStSxtT). All isolates were susceptible to cefotaxime and ceftazidime; 5 isolates obtained in 2004 were intermediately susceptible to cefepime (MIC 16 μg/mL) (Appendix Figure).
Overall, 8 PFGE strain types (A–H) and 6 clusters (1–6) were identified. All isolates that belonged to clusters 1, 2, and 4 were resistant to ciprofloxacin and to 8–11 other antimicrobial drugs. Two dominant patterns, B and F, were identified and included 16 and 10 ciprofloxacin-resistant isolates, respectively. Among 16 isolates of pattern B, 14 isolates showed the R-type AcAmCCpGNSStSxtT, and 1 was additionally resistant to kanamycin. In pattern F, 4 isolates showed the R-type AcAmCCpGNSStSxtT, and 5 were additionally resistant to kanamycin.
Point mutations in the QRDR of gyrA, parC, or parE were identified in 35 of 36 nalidixic acid–resistant isolates, whereas no gyrB mutations and no qnr plasmid were found. For 5 nalidixic acid–resistant and ciprofloxacin low-level–resistant isolates, 4 isolates harbored single (D87N) or double (S83F, D87N) mutations in GyrA, and no mutation was found in 1 isolate (ST6). All 31 ciprofloxacin-resistant isolates accumulated a minimum of 3 mutations: GyrA(S83F, D87N), ParC(S80R) (28 isolates) or GyrA(S83F, D87G), ParC(S80R) (3 isolates). Two ciprofloxacin-resistant isolates with PFGE pattern C and 1 isolate with PFGE pattern A2 harbored an additional mutation in ParE (S458P) (Figure).
Of 39 sulfamethoxazole-resistant isolates encompassing PFGE clusters 1, 2, 3, and 4, 37 possessed class 1 integrons. All class 1 integron–positive isolates were resistant to 6–12 antimicrobial drugs; 2 distinct class 1 integrons were identified in 37 isolates. Of isolates obtained from 2002 through 2005, 32 contained a 1.9-kb integron gene cassette dhfrXII-orfF-aadA2. In 2004 and 2005, 3 and 2 isolates, respectively, contained a 2-kb integron gene cassette blaOXA-30-aadA1. None of the 36 ampicillin-resistant isolates contained TEM or SHV enzyme, but OXA-30 gene was detected in 32 isolates, identical in DNA sequence to GenBank AF255921. All 32 isolates harboring OXA-30 enzyme showed MICs to cefepime of 2–16 μg/mL, whereas isolates lacking OXA-30 showed MICs to cefepime of <1>.
Conclusions
We report a high incidence of fluoroquinolone-resistant S. Typhimurium isolates from Tongji Hospital outpatients. The MIC variation for ciprofloxacin differed 2- to 4-fold in isolates that had the same QRDR mutation profile, which implies that other mechanisms might partially contribute to the resistance phenotype (Appendix Figure).
After PFGE analysis, S. Typhimurium isolates were grouped into 3 ciprofloxacin-susceptible clusters and ciprofloxacin-resistant clusters. Similar distribution patterns have also been observed in isolates from Japan (9), which suggests a distinct genetic lineage for ciprofloxacin-resistant isolates that have become dominant. Studies have reported that ciprofloxacin-resistant S. Typhimurium isolates were usually resistant to multiple drugs (9,10). In this study, all ciprofloxacin-resistant S. Typhimurium isolates were resistant to 8–11 additional antimicrobial drugs. Among the 32 isolates harboring OXA-30 enzyme in this study, only 5 with PFGE pattern F showed intermediate resistance to cefepime, which suggests different levels of OXA gene expression or the contribution of other unknown mechanisms.
The high incidence of quinonlone-resistant S. Typhimurium isolates in this study might be affected by several factors. First, patients infected by antimicrobial drug–resistant S. Typhimurium strains had higher rates of hospitalization than did patients infected by susceptible strains (11,12), and the isolates in this study were from a university-affiliated medical center that usually treats patients with severe illness. Second, US studies have estimated that half of outpatient antimicrobial drugs were inappropriately prescribed for conditions such as viral illness (13). In China, inappropriate prescriptions might be even more common because antimicrobial drug prescriptions in hospitals are a source of profit. Although we do not have patient antimicrobial drug–use information, the easy access to antimicrobial drugs raises the possibility that outpatients might have taken fluoroquinolones after the onset of the illness but before the collection of stool specimens. Third, because livestock products are a common source of salmonellosis, the dissemination of ciprofloxacin-resistant S. Typhimurium might have been facilitated by the use of fluoroquinolones in livestock production (2). Last, use of other antimicrobial drugs, such as ampicillin, gentamicin, or streptomycin, may also contribute to the spreading of fluoroquinolone-resistant S. Typhimurium because all the ciprofloxacin-resistant isolates were also resistant to 8–11 additional antimicrobial drugs.
Although fluoroquinolone-resistant isolates were prevalent in Tongji Hospital, ciprofloxacin is still empirically used to treat salmonellosis in adults, due partly to the absence of systematic surveillance programs to actively monitor antimicrobial drug resistance in Salmonella spp. Because local data on antimicrobial drug susceptibility are less available, we strongly recommend that hospitals and national and local health laboratories develop and maintain the capacity to perform Salmonella culture and in vitro susceptibility testing.
Acknowledgments
We thank Patrick F. McDermott for revision and helpful comments on the manuscript.
This research was supported by grant (2005DIB3J159) from the Ministry of Science and Technology of the People's Republic of China.
Dr Cui is a microbiologist in the National Center for Surveillance of Antimicrobial Resistance, the State Food and Drug Administration, Beijing, China. His professional interests include developing detection methods for bacterial pathogens, molecular epidemiology, and antimicrobial drug–resistance mechanisms of bacterial pathogens.
References
Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, et al. Food-related illness and death in the United States. Emerg Infect Dis. 1999;5:607–25.
Galanis E, Lo Fo Wong DM, Patrick ME, Binsztein N, Cieslik A, Chalermchikit T, et al. Web-based surveillance and global Salmonella distribution, 2000–2002. Emerg Infect Dis. 2006;12:381–8.
Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32:331–51.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; seventeenth informational supplement. Wayne (PA): The Institute; 2007 (document M100-S17).
Barrett TJ, Gerner-Smidt P, Swaminathan B. Interpretation of pulsed-field gel electrophoresis patterns in foodborne disease investigations and surveillance. Foodborne Pathog Dis. 2006;3:20–31.
Giraud E, Brisabois A, Martel JL, Chaslus-Dancla E. Comparative studies of mutations in animal isolates and experimental in vitro– and in vivo–selected mutants of Salmonella spp. suggest a counterselection of highly fluoroquinolone-resistant strains in the field. Antimicrob Agents Chemother. 1999;43:2131–7.
Levesque C, Piche L, Larose C, Roy PH. PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrob Agents Chemother. 1995;39:185–91.
Ouellette M, Bissonnette L, Roy PH. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci U S A. 1987;84:7378–82.
Izumiya H, Mori K, Kurazono T, Yamaguchi M, Higashide M, Konishi N, et al. Characterization of isolates of Salmonella enterica serovar Typhimurium displaying high-level fluoroquinolone resistance in Japan. J Clin Microbiol. 2005;43:5074–9.
Hakanen A, Kotilainen P, Huovinen P, Helenius H, Siitonen A. Reduced fluoroquinolone susceptibility in Salmonella enterica serotypes in travelers returning from Southeast Asia. Emerg Infect Dis. 2001;7:996–1003.
Varma JK, Molbak K, Barrett TJ, Beebe JL, Jones TF, Rabatsky-Ehr T, et al. Antimicrobial-resistant nontyphoidal Salmonella is associated with excess bloodstream infections and hospitalizations. J Infect Dis. 2005;191:554–61.
Martin LJ, Fyfe M, Dore K, Buxton JA, Pollari F, Henry B, et al. Increased burden of illness associated with antimicrobial-resistant Salmonella enterica serotype Typhimurium infections. J Infect Dis. 2004;189:377–84.
Nyquist AC, Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279:875–7.
CDC
Sunday, March 02, 2008
Saturday, March 01, 2008
Intracameral antibiotics: Questions for the United States based on prospective studies
Intracameral antibiotics: Questions for the United States based on prospective studies
J Cataract Refract Surg. 2008 Mar
Liesegang TJ.
From the Mayo Clinic, Jacksonville, Florida, USA.
Recent prospective studies from Europe suggest the use of intracameral antibiotics for prophylaxis of endophthalmitis, although the studies did not make a comparison with the most common United States prophylaxis techniques. Thus, the European studies as well as the present literature were reviewed in an attempt to place the European studies in perspective with regard to the present U.S. protocol and the available literature. There is no worldwide-established approach to prophylaxis of endophthalmitis. In the absence of a strong evidence-based approach most surgeons use surrogate studies to support their techniques and mold their opinions based on their interpretation of the literature and when they believe organisms causing endophthalmitis enter the eye. The review showed that preoperative topical antibiotics limit the number of bacteria on the ocular surface at surgery and postoperative topical antibiotics are most appropriate to address postoperative inoculation until the wound is sealed (with no tapering). Whereas intracameral antibiotic injection may be an appropriate route of administration to address inoculation occurring at the time of surgery, more research on safety and effectiveness is needed before we expose the millions of eyes having cataract surgery each year. A multipronged approach to limit endophthalmitis risk is also needed, with antibiotics as only part of the strategy.
Elsevier
J Cataract Refract Surg. 2008 Mar
Liesegang TJ.
From the Mayo Clinic, Jacksonville, Florida, USA.
Recent prospective studies from Europe suggest the use of intracameral antibiotics for prophylaxis of endophthalmitis, although the studies did not make a comparison with the most common United States prophylaxis techniques. Thus, the European studies as well as the present literature were reviewed in an attempt to place the European studies in perspective with regard to the present U.S. protocol and the available literature. There is no worldwide-established approach to prophylaxis of endophthalmitis. In the absence of a strong evidence-based approach most surgeons use surrogate studies to support their techniques and mold their opinions based on their interpretation of the literature and when they believe organisms causing endophthalmitis enter the eye. The review showed that preoperative topical antibiotics limit the number of bacteria on the ocular surface at surgery and postoperative topical antibiotics are most appropriate to address postoperative inoculation until the wound is sealed (with no tapering). Whereas intracameral antibiotic injection may be an appropriate route of administration to address inoculation occurring at the time of surgery, more research on safety and effectiveness is needed before we expose the millions of eyes having cataract surgery each year. A multipronged approach to limit endophthalmitis risk is also needed, with antibiotics as only part of the strategy.
Elsevier
Antimicrobials as a contributory factor in oral candidosis - a brief overview
Antimicrobials as a contributory factor in oral candidosis - a brief overview
Oral Dis. 2008 Mar
Oral Dis. 2008 Mar
Soysa NS, Samaranayake LP, Ellepola AN.
Division of Pharmacology, Department of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka; 2Oral Bio-Sciences, Faculty of Dentistry, University of Hong Kong, Hong Kong; 3Department of Bioclinical Sciences, Faculty of Dentistry, Health Sciences Center, Kuwait University, Kuwait
Dr NS Soysa, Division of Pharmacology, Department of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka. Tel: 94-81-2387500, Fax: 94-81-2388948, E-mail: niroshanis@pdn.ac.lk/hnsnit@yahoo.com
The advent of the human immunodeficiency virus infection and the increasing prevalence of compromised individuals in the community due to modern therapeutic advances have resulted in a resurgence of opportunistic infections, including oral candidosis, which is by far the most common oral fungal infection in man. Broad-spectrum antibiotics used in the treatment of a wide range of disease conditions have also been attributed as a predisposing factor of oral candidosis. In this mini review we discuss the research findings on the relationship between antibiotics and oral candidosis and possible mechanisms of pathogenicity following such therapy.
Effect and Mechanism of Andrographolide on the Recovery of Pseudomonas aeruginosa Susceptibility to Several Antibiotics
Effect and Mechanism of Andrographolide on the Recovery of Pseudomonas aeruginosa Susceptibility to Several Antibiotics
J Int Med Res. 2008 Jan-Feb
Wu CM, Cao JL, Zheng MH, Ou Y, Zhang L, Zhu XQ, Song JX.Department of Liver Diseases, The Traditional Chinese Medical Hospital of Wenzhou, Wenzhou, China.
Effectiveness and mechanism of action of andrographolide on the recovery of Pseudomonas aeruginosa susceptibility to antibiotics was investigated. In the presence of andrographolide, the Mueller-Hinton broth dilution method measured minimal inhibitory concentrations (MIC) of ceftazidine, cefpirome, chloramphenicol, L-ofloxacin, kanamycin, imipenem and meropenem. Real-time fluorescence quantitative polymerase chain reaction was used to determine mexB mRNA expressions in P. aeruginosa PAO1 strain and MexAB-OprM overexpressing strain. Relative mexB mRNA expression was detected in both strains incubated for 3 and 9 h. When andrographolide-treated groups were compared with controls, the MIC of ceftazidine, cefpirome, L-ofloxacin and meropenem for both strains decreased, and the relative mexB mRNA expression was significantly lower, although between andrographolide groups there were no significant differences. Compared with the inactivated quorum-sensing system, relative amounts of mexB mRNA in the PAO1 strain and MexAB-OprM overexpressing strain in the activated quorum-sensing system increased 10- and 30-fold, respectively. Andrographolide recovered P. aeruginosa susceptibility to antibiotics and reduced the MexAB-OprM efflux pump expression level.
PMID: 18304418 [PubMed - in process]
J Int Med Res. 2008 Jan-Feb
Wu CM, Cao JL, Zheng MH, Ou Y, Zhang L, Zhu XQ, Song JX.Department of Liver Diseases, The Traditional Chinese Medical Hospital of Wenzhou, Wenzhou, China.
Effectiveness and mechanism of action of andrographolide on the recovery of Pseudomonas aeruginosa susceptibility to antibiotics was investigated. In the presence of andrographolide, the Mueller-Hinton broth dilution method measured minimal inhibitory concentrations (MIC) of ceftazidine, cefpirome, chloramphenicol, L-ofloxacin, kanamycin, imipenem and meropenem. Real-time fluorescence quantitative polymerase chain reaction was used to determine mexB mRNA expressions in P. aeruginosa PAO1 strain and MexAB-OprM overexpressing strain. Relative mexB mRNA expression was detected in both strains incubated for 3 and 9 h. When andrographolide-treated groups were compared with controls, the MIC of ceftazidine, cefpirome, L-ofloxacin and meropenem for both strains decreased, and the relative mexB mRNA expression was significantly lower, although between andrographolide groups there were no significant differences. Compared with the inactivated quorum-sensing system, relative amounts of mexB mRNA in the PAO1 strain and MexAB-OprM overexpressing strain in the activated quorum-sensing system increased 10- and 30-fold, respectively. Andrographolide recovered P. aeruginosa susceptibility to antibiotics and reduced the MexAB-OprM efflux pump expression level.
PMID: 18304418 [PubMed - in process]
Tuesday, February 26, 2008
Prophylactic antibiotics given within 24 hours of surgery, compared with antibiotics given for 72 hours perioperatively increased rate of MRSA
Prophylactic antibiotics given within 24 hours of surgery, compared with antibiotics given for 72 hours perioperatively, increased the rate of methicillin-resistant Staphylococcus aureus isolated from surgical site infections
J Infect Chemother. 2008 Feb
Kusachi S, Sumiyama Y, Nagao J, Arima Y, Yoshida Y, Tanaka H, Nakamura Y, Saida Y, Watanabe M, Watanabe R, Sato J.
Third Department of Surgery, Toho University Ohashi Medical Center Hospital, 2-17-6 Ohashi, Meguro-ku, Tokyo, 153-8515, Japan, kusachi@med.toho-u.ac.jp.
The purpose of this research was to find which method better prevented MRSA isolation from postoperative infection sites: the administration of postoperative infection control agents within 72 h of surgery, including the day of surgery, or the administration of these agents within 24 h of surgery. More than 3000 patients who underwent elective surgery of the digestive system were studied. Cefazolin or cefotiam was used as the prophylactic antibiotic. The number of patients, sex, age, clinical stage, incidence of surgical site infection (SSI), isolated bacteria, distal pancreatectomy with or without gastrectomy, the rate of laparoscopic surgery, and the rate of abdominoperineal resection (APR) were examined in a prospective controlled study over three time periods. There were no significant differences in the demographics of patients in the three periods. The duration of antibiotic administration was 96.1 +/- 11.2 h in period A, 18.2 +/- 2.7 h in period B, and 66.9 +/- 11.1 hours in period C (P less then 0.05). There was no significant difference in the incidence of SSI in the three periods. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the infectious site in 0.47% of patients in period A, and from 2.1% and 0.34% of patients in periods B and C, respectively, and the incidence of MRSA was significantly higher in period B as compared with periods A and C. The isolation rates of MRSA and methicillin-sensitive S. aureus (MSSA) were both significantly higher in period B patients. We concluded that the administration of prophylactic antibiotics within 24 h of surgery increased the rate of isolation of MRSA.
Springer Link
J Infect Chemother. 2008 Feb
Kusachi S, Sumiyama Y, Nagao J, Arima Y, Yoshida Y, Tanaka H, Nakamura Y, Saida Y, Watanabe M, Watanabe R, Sato J.
Third Department of Surgery, Toho University Ohashi Medical Center Hospital, 2-17-6 Ohashi, Meguro-ku, Tokyo, 153-8515, Japan, kusachi@med.toho-u.ac.jp.
The purpose of this research was to find which method better prevented MRSA isolation from postoperative infection sites: the administration of postoperative infection control agents within 72 h of surgery, including the day of surgery, or the administration of these agents within 24 h of surgery. More than 3000 patients who underwent elective surgery of the digestive system were studied. Cefazolin or cefotiam was used as the prophylactic antibiotic. The number of patients, sex, age, clinical stage, incidence of surgical site infection (SSI), isolated bacteria, distal pancreatectomy with or without gastrectomy, the rate of laparoscopic surgery, and the rate of abdominoperineal resection (APR) were examined in a prospective controlled study over three time periods. There were no significant differences in the demographics of patients in the three periods. The duration of antibiotic administration was 96.1 +/- 11.2 h in period A, 18.2 +/- 2.7 h in period B, and 66.9 +/- 11.1 hours in period C (P less then 0.05). There was no significant difference in the incidence of SSI in the three periods. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the infectious site in 0.47% of patients in period A, and from 2.1% and 0.34% of patients in periods B and C, respectively, and the incidence of MRSA was significantly higher in period B as compared with periods A and C. The isolation rates of MRSA and methicillin-sensitive S. aureus (MSSA) were both significantly higher in period B patients. We concluded that the administration of prophylactic antibiotics within 24 h of surgery increased the rate of isolation of MRSA.
Springer Link
Saturday, February 23, 2008
Daptomycin: a new treatment for insidious infections due to gram-positive pathogens
Daptomycin: a new treatment for insidious infections due to gram-positive pathogens
February 2008
Cottagnoud P.
Department of Internal Medicine, Inselspital, Bern, Switzerland. Philippe.Cottagnoud@insel.ch.
Daptomycin, a new lipopeptide antibiotic, is highly bactericidal against the majority of Grampositive human pathogens, including methicillinresistant (MRSA) and vancomycin-resistant enterococci. Its mechanism of action is unique resulting in the destruction of the membrane potential without lysing the cell wall. The mechanism of action of daptomycin, its antibacterial spectrum, the development of resistance and pre- and clinical studies are discussed in this review.
PMID: 18293118 [PubMed - in process]
February 2008
Cottagnoud P.
Department of Internal Medicine, Inselspital, Bern, Switzerland. Philippe.Cottagnoud@insel.ch.
Daptomycin, a new lipopeptide antibiotic, is highly bactericidal against the majority of Grampositive human pathogens, including methicillinresistant (MRSA) and vancomycin-resistant enterococci. Its mechanism of action is unique resulting in the destruction of the membrane potential without lysing the cell wall. The mechanism of action of daptomycin, its antibacterial spectrum, the development of resistance and pre- and clinical studies are discussed in this review.
PMID: 18293118 [PubMed - in process]
Friday, February 22, 2008
Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial.
Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial.
Int J Dermatol. 2008 Mar
Akhyani M, Ehsani AH, Ghiasi M, Jafari AK.
Department of Dermatology, Razi Hospital, Tehran, Iran.
BACKGROUND: Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne.
METHODS: For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty-seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness.
RESULTS: Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline.
CONCLUSION: This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea.
PMID: 18289334 [PubMed - in process]
Int J Dermatol. 2008 Mar
Akhyani M, Ehsani AH, Ghiasi M, Jafari AK.
Department of Dermatology, Razi Hospital, Tehran, Iran.
BACKGROUND: Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne.
METHODS: For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty-seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness.
RESULTS: Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline.
CONCLUSION: This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea.
PMID: 18289334 [PubMed - in process]
Monday, February 18, 2008
Two New Members of Streptothricin Class Antibiotics from Streptomyces qinlingensis sp. nov.
Two New Members of Streptothricin Class Antibiotics from Streptomyces qinlingensis sp. nov.
J Antibiot (Tokyo). 2008
Ji Z, Wang M, Zhang J, Wei S, Wu W.
Institute of Pesticide Science, Northwest Agricultural & Forestry University.
J Antibiot (Tokyo). 2008
Ji Z, Wang M, Zhang J, Wei S, Wu W.
Institute of Pesticide Science, Northwest Agricultural & Forestry University.
Keywords: Streptomyces qinlingensis, streptothricin, structural elucidation
Four streptothricin-group antibiotics (1~4) were isolated from the fermentation broth of Streptomyces qinlingensis sp. nov. Along with the known antibiotics streptothricins F (1) and D (3), two new members of this class (2, 4) were identified as 12-carbamoyl derivatives of 1 and 3, respectively, mainly by analysis of the IR, HR-MS and NMR spectral data. The antibacterial activities of 1~4 against Escherichia coli (MICs 3.1, 25.0, 3.1 and 12.5 mug/ml), Bacillus subtilis (MICs 6.3, 25.0, 3.1 and 50 mug/ml), Staphylococcus aureus (MICs 12.5, >100.0, 6.3, >100.0 mug/ml), Bacillus cereus (MICs 25.0, 50.0, 25.0 and 50.0 mug/ml) and Pseudomonas aeruginosa (MICs 50.0, >100.0, 50.0, >100.0 mug/ml) were assayed by micro-broth dilution.
The results based on MIC data indicated that 2 and 4 exhibited significantly less potent antibacterial activities when compared to that of 1 and 3.
Journal of Antibiotics
Saturday, February 16, 2008
Gatifloxacin Produces Both Hypoglycemia and Hyperglycemia: A Retrospective Study
Gatifloxacin Produces Both Hypoglycemia and Hyperglycemia: A Retrospective Study.
Am J Med Sci. 2008 Feb
Haerian H, McHugh P, Brown R, Somes G, Solomon SS.
From Research (sss), Medical (hh, pm, sss), and Pharmacy Services, VAMC Memphis, Memphis, Tennessee; and the Departments of Medicine (hh, pm, sss), Pharmacology (sss), and Preventive Medicine (gs) of the College of Medicine and College of Pharmacy (rb), University of Tennessee, the Health Science Center, Memphis, Tennessee.
BACKGROUND: Gatifloxacin, until recently one of the most commonly prescribed antibiotics, has been shown to produce hypoglycemia.
METHODS: To further examine the effects of Gatifloxicin (G) on blood glucose (BS), we conducted a retrospective chart review on 264 inpatients, examining for both hypoglycemia and hyperglycemia, comparing G with another quinolone, Ciproflaxin (C), and nonquinolone, Ceftriaxone (R).
RESULTS: We found that of 292 patient encounters, 28 hypoglycemia and 48 hyperglycemic events occurred. Patients given G were 5 times as likely to become hypoglycemic as C
CONCLUSIONS: In summary, G was clearly associated with both hypoglycemia and hyperglycemia compared with C and R. The risk of hyperglycemia increased in the presence of DM, steroid use, and "sick enough" to be in the intensive care unit.
PMID: 18277115 [PubMed - as supplied by publisher]
Am J Med Sci. 2008 Feb
Haerian H, McHugh P, Brown R, Somes G, Solomon SS.
From Research (sss), Medical (hh, pm, sss), and Pharmacy Services, VAMC Memphis, Memphis, Tennessee; and the Departments of Medicine (hh, pm, sss), Pharmacology (sss), and Preventive Medicine (gs) of the College of Medicine and College of Pharmacy (rb), University of Tennessee, the Health Science Center, Memphis, Tennessee.
BACKGROUND: Gatifloxacin, until recently one of the most commonly prescribed antibiotics, has been shown to produce hypoglycemia.
METHODS: To further examine the effects of Gatifloxicin (G) on blood glucose (BS), we conducted a retrospective chart review on 264 inpatients, examining for both hypoglycemia and hyperglycemia, comparing G with another quinolone, Ciproflaxin (C), and nonquinolone, Ceftriaxone (R).
RESULTS: We found that of 292 patient encounters, 28 hypoglycemia and 48 hyperglycemic events occurred. Patients given G were 5 times as likely to become hypoglycemic as C
CONCLUSIONS: In summary, G was clearly associated with both hypoglycemia and hyperglycemia compared with C and R. The risk of hyperglycemia increased in the presence of DM, steroid use, and "sick enough" to be in the intensive care unit.
PMID: 18277115 [PubMed - as supplied by publisher]
Sunday, February 03, 2008
Ceftobiprole Medocaril with Vancomycin plus Ceftazidime for the Treatment of Patients with Complicated Skin Infections
A Randomized, Double-Blind Trial Comparing Ceftobiprole Medocaril with Vancomycin plus Ceftazidime for the Treatment of Patients with Complicated Skin and Skin-Structure Infections.
Jan 2008
Noel GJ, Bush K, Bagchi P, Ianus J, Strauss RS.
Johnson & Johnson Pharmaceutical Research and Development, Raritan, New Jersey.
Background: A randomized, double-blind, multicenter trial involving patients with a broad range of complicated skin and skin-structure infections due to either gram-positive or gram-negative bacteria was conducted to compare ceftobiprole monotherapy with treatment with vancomycin plus ceftazidime.
Methods: Patients were randomized 2:1 to receive ceftobiprole or to receive vancomycin plus ceftazidime. Outcomes were determined at a test-of-cure visit (7-14 days after completion of therapy) and were analyzed for all patients with complicated skin and skin-structure infections, as well as for subgroups, on the basis of major types of infections and severity of disease.
Results: Among the clinically evaluable and the intent-to-treat populations, clinical cure rates at the test-of-cure visit were similar in the ceftobiprole and comparator treatment arms (clinical cure rate, 90.5% [439 of 485 patients] and 90.2% [220 of 244 patients] in the clinically evaluable population, respectively; 81.9% [448 of 547 patients] and 80.8% [227 of 281 patients] in the intent-to-treat population, respectively). Clinical cure rates in ceftobiprole-treated patients ranged from 86.2% (125 of 145 patients) among those with diabetes who had foot infections to 93.0% (80 of 86 patients) among those with cellulitis.
Among patients treated with ceftobiprole, clinical cure rates were similar among patients from whom gram-negative bacteria were isolated (87.9% [109 of 124 patients]) and among patients from whom gram-positive bacteria were isolated (91.8% [292 of 318 patients]) and were not statistically different from the clinical cure rates among comparator-treated patients (89.7% [61 of 68 patients] and 90.3% [149 of 165 patients], respectively). Rates of adverse events and serious adverse events in the 2 treatment groups were similar.
Conclusions: Ceftobiprole monotherapy is as effective as vancomycin plus ceftazidime for treating patients with a broad range of complicated skin and skin-structure infections and infections due to gram-positive and gram-negative bacteria.
PMID: 18225981 [PubMed - as supplied by publisher]
Jan 2008
Noel GJ, Bush K, Bagchi P, Ianus J, Strauss RS.
Johnson & Johnson Pharmaceutical Research and Development, Raritan, New Jersey.
Background: A randomized, double-blind, multicenter trial involving patients with a broad range of complicated skin and skin-structure infections due to either gram-positive or gram-negative bacteria was conducted to compare ceftobiprole monotherapy with treatment with vancomycin plus ceftazidime.
Methods: Patients were randomized 2:1 to receive ceftobiprole or to receive vancomycin plus ceftazidime. Outcomes were determined at a test-of-cure visit (7-14 days after completion of therapy) and were analyzed for all patients with complicated skin and skin-structure infections, as well as for subgroups, on the basis of major types of infections and severity of disease.
Results: Among the clinically evaluable and the intent-to-treat populations, clinical cure rates at the test-of-cure visit were similar in the ceftobiprole and comparator treatment arms (clinical cure rate, 90.5% [439 of 485 patients] and 90.2% [220 of 244 patients] in the clinically evaluable population, respectively; 81.9% [448 of 547 patients] and 80.8% [227 of 281 patients] in the intent-to-treat population, respectively). Clinical cure rates in ceftobiprole-treated patients ranged from 86.2% (125 of 145 patients) among those with diabetes who had foot infections to 93.0% (80 of 86 patients) among those with cellulitis.
Among patients treated with ceftobiprole, clinical cure rates were similar among patients from whom gram-negative bacteria were isolated (87.9% [109 of 124 patients]) and among patients from whom gram-positive bacteria were isolated (91.8% [292 of 318 patients]) and were not statistically different from the clinical cure rates among comparator-treated patients (89.7% [61 of 68 patients] and 90.3% [149 of 165 patients], respectively). Rates of adverse events and serious adverse events in the 2 treatment groups were similar.
Conclusions: Ceftobiprole monotherapy is as effective as vancomycin plus ceftazidime for treating patients with a broad range of complicated skin and skin-structure infections and infections due to gram-positive and gram-negative bacteria.
PMID: 18225981 [PubMed - as supplied by publisher]
Saturday, January 19, 2008
Population pharmacokinetic and pharmacodynamic modeling of norvancomycin.
Population pharmacokinetic and pharmacodynamic modeling of norvancomycin.
Eur J Clin Microbiol Infect Dis. 2008 Jan 9
Eur J Clin Microbiol Infect Dis. 2008 Jan 9
Zhang J, Zhang Y, Shi Y, Rui J, Yu J, Cao G, Wu J.
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China, zhangj61@fudan.edu.cn.
In this paper, population pharmacokinetics (PPK) and pharmacodynamics of norvancomycin in patients were investigated. The studied dataset was derived from 146 patients with confirmed or suspected gram-positive bacterial infections, as well as 20 healthy volunteers. A PPK model was developed and validated by the nonlinear mixed effect model (NONMEM) software. The norvancomycin minimum inhibitory concentrations (MICs) for the isolates from patients were determined by the agar dilution method. The best model was a two-compartment pharmacokinetic model with exponential inter-individual error and an additive residual error statistic model.
The findings of the present study indicated that the change in CLcr values had different effects on drug clearance (CL). In patients with renal dysfunction (CLcr85 ml/min), CL=6.0.(WT/60)(0.52). An increased volume of peripheral distribution (V(2)) was observed when norvancomycin was co-administered with diuretics. Inter-individual variability in CL, V(1), Q, and V(2) was 35.92%, 11.40%, 0, and 79.75%, respectively. Residual variability was 3.05 mg/L.
The logistic stepwise analyses revealed that only the ratio of AUC(24) /MIC was a major factor which could significantly predict the clinical outcome and bacterial eradication in patients. As the AUC(24)/MIC ratio was >579.90 for staphylococcal infection and >637.67 for enterococcal infections, approximately 95% of patients would be predicted to achieve a cured clinical outcome.
In conclusion, AUC(24)/MIC should be a major pharmacokinetics/pharmacodynamics (PK/PD) parameter to predict the clinical efficacy of norvancomycin. An optimized regimen of norvancomycin can be simulated and developed for different subgroups of patients who have special physiologic and pathologic conditions.
Springerlink
Monday, December 24, 2007
Optimizing Therapy for Stenotrophomonas maltophilia.
Optimizing Therapy for Stenotrophomonas maltophilia.
Semin Respir Crit Care Med. 2007 Dec
Muder RR.
Infectious Disease Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
STENOTROPHOMONAS (XANTHOMONAS) MALTOPHILIA is a nonfermentative, gram-negative bacillus that is widely distributed in natural and humanmade environments. In the nonhospital setting it is an uncommon pathogen, typically causing soft tissue infection of contaminated wounds. In the hospital setting, particularly among critical care and oncology patients, S. MALTOPHILIA may cause catheter-related bacteremia, pneumonia, soft tissue infection, meningitis, prosthetic valve endocarditis, and ocular infections. S. MALTOPHILIA is usually resistant to multiple antimicrobials, including expanded-spectrum penicillins, third-generation cephalosporins, carbapenems, aminoglycosides, and quinolones. Trimethoprim-sulfamethoxazole is the antimicrobial agent of choice for this pathogen but is bacteriostatic. Further, resistance to this agent is increasing. Certain combinations of antibiotics are synergistic and may be appropriate for patients harboring resistant organisms or with life-threatening infections.
Thieme Connect
Semin Respir Crit Care Med. 2007 Dec
Muder RR.
Infectious Disease Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
STENOTROPHOMONAS (XANTHOMONAS) MALTOPHILIA is a nonfermentative, gram-negative bacillus that is widely distributed in natural and humanmade environments. In the nonhospital setting it is an uncommon pathogen, typically causing soft tissue infection of contaminated wounds. In the hospital setting, particularly among critical care and oncology patients, S. MALTOPHILIA may cause catheter-related bacteremia, pneumonia, soft tissue infection, meningitis, prosthetic valve endocarditis, and ocular infections. S. MALTOPHILIA is usually resistant to multiple antimicrobials, including expanded-spectrum penicillins, third-generation cephalosporins, carbapenems, aminoglycosides, and quinolones. Trimethoprim-sulfamethoxazole is the antimicrobial agent of choice for this pathogen but is bacteriostatic. Further, resistance to this agent is increasing. Certain combinations of antibiotics are synergistic and may be appropriate for patients harboring resistant organisms or with life-threatening infections.
Thieme Connect
Optimizing Use of beta-Lactam Antibiotics in the Critically Ill.
Optimizing Use of beta-Lactam Antibiotics in the Critically Ill.
Semin Respir Crit Care Med. 2007 Dec
Roberts JA, Lipman J.
Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia.
The escalation of serious infections in critically ill patients over the past 25 years has continued despite advances in contemporary medicine. Ongoing research to reduce the high morbidity and mortality rates is mandated. beta-lactam antibiotics are often used empirically in serious infections. The efficacy of these time-dependent antibiotics is correlated with the time that concentrations are maintained above the minimum inhibitory concentration of the infective pathogen. In critically ill patients, pathophysiological changes can reduce antibiotic concentrations and thus alternative modes of administration such as continuous infusion have been studied and shown to standardize beta-lactam pharmacokinetics and meet pharmacodynamic targets. Clinical data supporting the efficacy of continuous infusion are currently scarce, but data continue to grow. Likewise antibiotic resistance continues to grow. Recent data suggest that poor dosing strategies may be contributing to this problem, which is exacerbated by a lack of development of alternate antibiotics. Suffice to say clinicians must use antibiotic regimens that optimally treat the individual patient and reduce the development of antibiotic resistance.
Thieme Connect
Semin Respir Crit Care Med. 2007 Dec
Roberts JA, Lipman J.
Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia.
The escalation of serious infections in critically ill patients over the past 25 years has continued despite advances in contemporary medicine. Ongoing research to reduce the high morbidity and mortality rates is mandated. beta-lactam antibiotics are often used empirically in serious infections. The efficacy of these time-dependent antibiotics is correlated with the time that concentrations are maintained above the minimum inhibitory concentration of the infective pathogen. In critically ill patients, pathophysiological changes can reduce antibiotic concentrations and thus alternative modes of administration such as continuous infusion have been studied and shown to standardize beta-lactam pharmacokinetics and meet pharmacodynamic targets. Clinical data supporting the efficacy of continuous infusion are currently scarce, but data continue to grow. Likewise antibiotic resistance continues to grow. Recent data suggest that poor dosing strategies may be contributing to this problem, which is exacerbated by a lack of development of alternate antibiotics. Suffice to say clinicians must use antibiotic regimens that optimally treat the individual patient and reduce the development of antibiotic resistance.
Thieme Connect
Optimizing Therapy for Infections Caused by Enterobacteriaceae Producing Extended-Spectrum beta-Lactamases.
Optimizing Therapy for Infections Caused by Enterobacteriaceae Producing Extended-Spectrum beta-Lactamases.
Semin Respir Crit Care Med. 2007 Dec
Endimiani A, Paterson DL.
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Semin Respir Crit Care Med. 2007 Dec
Endimiani A, Paterson DL.
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
The spread of multidrug-resistant Enterobacteriaceae is complicating the treatment of nosocomial infections. In many parts of the world, resistance to third-generation cephalosporins exceeds 10% of total nosocomial isolates and 30% of isolates detected in the intensive care unit. This resistance is frequently due to the acquisition of plasmids containing genes encoding for extended-spectrum beta-lactamases (ESBLs). Furthermore, these mobile elements often carry genes encoding resistance to other drugs such as aminoglycosides. A high risk of poor clinical outcome has been observed in patients infected with ESBL producers receiving third-generation cephalosporins, even if the organism appears susceptible to the antibiotic. For this reason, clinical microbiology laboratories are advised to incorporate specific ESBL detection methodology into routine clinical practice. This should prevent erroneous use of cephalosporins for these infections. Most ESBL producers remain susceptible to carbapenems, and these agents are considered the drugs of choice against ESBL-producing organisms. Unfortunately, there is now an increasing occurrence of carbapenem resistance in the Enterobacteriaceae. In this context, clinical response to new antibiotics (e.g., tigecycline) and old antibiotics (e.g., colistin) with good in vitro activity against ESBL producers needs to be evaluated.
Thieme Connect
Optimizing use of colistin and polymyxin B in the critically ill.
Optimizing use of colistin and polymyxin B in the critically ill.
Semin Respir Crit Care Med. 2007 Dec
Nation RL, Li J.
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
Semin Respir Crit Care Med. 2007 Dec
Nation RL, Li J.
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
Polymyxin B and colistin are being used increasingly for the treatment of infections caused by gram-negative bacteria that are resistant to all other currently available antibiotics. Although the polymyxins have been available in the clinic for around 50 years, they have never been subjected to the drug development procedures required of modern pharmaceuticals. As a result, the available knowledge on the pharmacokinetics (PK), pharmacodynamics (PD), and toxicodynamics (TD) of the polymyxins is limited. Although significant advances have been made in the last 5 years or so, there are still large gaps in our understanding of the PK, PD, and TD, and of the PK/PD and PK/TD relationships. This information is required to generate recommendations on dosage regimens for various categories of critically ill patients. This paper reviews the growing understanding of the pharmacology of the polymyxins and factors that may impact on the optimization of the dose of these antibiotics in critically ill patients.
Thieme Connect
Optimizing antipseudomonal therapy in critical care
Optimizing antipseudomonal therapy in critical care
Iredell JR.
Centre for Infectious Diseases and Microbiology, University of Sydney/Westmead Hospital, Westmead, Australia.
PSEUDOMONAS AERUGINOSA is a common and important pathogen in the critically ill. It combines environmental hardiness with genomic plasticity and is well adapted to the various niches available in the intensive care unit (ICU). Unresolved arguments over the value of dual versus monotherapy relate primarily to rapidity of killing and to the avoidance of therapeutic failure due to antibiotic resistance. Increasing resistance to conventional antibiotics means that we need to be aware of the factors that promote the success of this pathogen in the ICU, and of emerging alternative strategies. This review focuses on an understanding of the underlying issues and on the practical aspects of prescribing, particularly in the ICU.
Thieme Connect
Iredell JR.
Centre for Infectious Diseases and Microbiology, University of Sydney/Westmead Hospital, Westmead, Australia.
PSEUDOMONAS AERUGINOSA is a common and important pathogen in the critically ill. It combines environmental hardiness with genomic plasticity and is well adapted to the various niches available in the intensive care unit (ICU). Unresolved arguments over the value of dual versus monotherapy relate primarily to rapidity of killing and to the avoidance of therapeutic failure due to antibiotic resistance. Increasing resistance to conventional antibiotics means that we need to be aware of the factors that promote the success of this pathogen in the ICU, and of emerging alternative strategies. This review focuses on an understanding of the underlying issues and on the practical aspects of prescribing, particularly in the ICU.
Thieme Connect
Friday, December 21, 2007
Optimizing Therapy for Vancomycin-Resistant Enterococci (VRE).
Optimizing Therapy for Vancomycin-Resistant Enterococci (VRE).
Semin Respir Crit Care Med. 2007 Dec
Linden PK.
Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Enterococci are gram-positive, facultative bacteria with low intrinsic virulence but capable of causing a diverse variety of infections such as bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection. During the past 2 decades the incidence of hospital-acquired enterococcal infection has significantly risen and is increasingly due to multidrug-resistant strains, primarily to the coacquisition of genetic determinants that encode for the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide resistance. Because enterococci constitute part of the normal colonizing flora, careful clinical interpretation of cultures that grow enterococci is paramount to avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based regimen, or vancomycin in a penicillin-intolerant individual. The need for a bactericidal combination with a cell-wall active agent combined with an aminoglycoside is most supported for native- or prosthetic valve endocarditis but is unproven for the majority of infections due to enterococci. The emergence of vancomycin-resistant enterococci prompted the clinical development of several novel and modified antimicrobial compounds approved for VRE infection (quinupristin-dalfopristin, linezolid) and several approved for non-VRE indications (daptomycin, tigecycline). There is a paucity of comparative clinical trial data with these new agents, although linezolid, based upon its efficacy and tolerability, appears to be the cornerstone of current treatment approaches. Despite a relatively short period of clinical use, enterococcal resistance has now been described for quinupristin-dalfopristin and linezolid and more recently even for daptomycin and tigecycline. Moreover, the optimal treatment of endocarditis due to VRE strains is unknown because, with the exception of daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial measures to treat VRE infection, such as foreign body removal and percutaneous or surgical drainage of close-spaced infection, reduce both the need for and the duration of anti-enterococcal treatment and the emergence of resistance to the newer antimicrobials.
PMID: 18095227 [PubMed - in process]
Semin Respir Crit Care Med. 2007 Dec
Linden PK.
Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Enterococci are gram-positive, facultative bacteria with low intrinsic virulence but capable of causing a diverse variety of infections such as bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection. During the past 2 decades the incidence of hospital-acquired enterococcal infection has significantly risen and is increasingly due to multidrug-resistant strains, primarily to the coacquisition of genetic determinants that encode for the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide resistance. Because enterococci constitute part of the normal colonizing flora, careful clinical interpretation of cultures that grow enterococci is paramount to avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based regimen, or vancomycin in a penicillin-intolerant individual. The need for a bactericidal combination with a cell-wall active agent combined with an aminoglycoside is most supported for native- or prosthetic valve endocarditis but is unproven for the majority of infections due to enterococci. The emergence of vancomycin-resistant enterococci prompted the clinical development of several novel and modified antimicrobial compounds approved for VRE infection (quinupristin-dalfopristin, linezolid) and several approved for non-VRE indications (daptomycin, tigecycline). There is a paucity of comparative clinical trial data with these new agents, although linezolid, based upon its efficacy and tolerability, appears to be the cornerstone of current treatment approaches. Despite a relatively short period of clinical use, enterococcal resistance has now been described for quinupristin-dalfopristin and linezolid and more recently even for daptomycin and tigecycline. Moreover, the optimal treatment of endocarditis due to VRE strains is unknown because, with the exception of daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial measures to treat VRE infection, such as foreign body removal and percutaneous or surgical drainage of close-spaced infection, reduce both the need for and the duration of anti-enterococcal treatment and the emergence of resistance to the newer antimicrobials.
PMID: 18095227 [PubMed - in process]
Perioperative antibiotics and anti-inflammatory agents in cataract surgery.
Perioperative antibiotics and anti-inflammatory agents in cataract surgery.
Curr Opin Ophthalmol. 2008 Jan
Decroos FC, Afshari NA.
Duke University Eye Center, Duke University Medical Center, Durham, North Carolina, USA.
PURPOSE OF REVIEW: Cataract surgery has benefited from great technical advances but no consensus exists as regards optimal perioperative medical management of inflammation and infection prophylaxis.
RECENT FINDINGS: The present article primarily reviews recent evidence about the most advantageous antibiotic regimen to minimize endophthalmitis, and the utility of steroids or nonsteroidal anti-inflammatory drugs (NSAIDs) in management of both postoperative inflammation and cystoid macular edema. Prospective data from Europe supports the efficacy of intracameral cephalosporins in reducing the incidence of endophthalmitis. We compare this with retrospective data from the United States describing a low incidence of endophthalmitis when using fourth-generation fluoroquinolones as chemoprophylaxis. Other studies demonstrate the anti-inflammatory effect of multiple perioperative topical NSAIDs. Further important questions remain, however, including whether NSAIDs exhibit a superior side-effect profile relative to corticosteroids, whether benefit exists to combination NSAID/corticosteroid therapy, as well as whether NSAIDS can reduce the incidence of cystoid macular edema.
SUMMARY: New evidence clarifies the use of intracameral antibiotics, and other studies support a niche anti-inflammatory role for NSAIDs.
PMID: 18090893 [PubMed - in process]
The role of NSAIDs in the management of postoperative ophthalmic inflammation.
Curr Opin Ophthalmol. 2008 Jan
Decroos FC, Afshari NA.
Duke University Eye Center, Duke University Medical Center, Durham, North Carolina, USA.
PURPOSE OF REVIEW: Cataract surgery has benefited from great technical advances but no consensus exists as regards optimal perioperative medical management of inflammation and infection prophylaxis.
RECENT FINDINGS: The present article primarily reviews recent evidence about the most advantageous antibiotic regimen to minimize endophthalmitis, and the utility of steroids or nonsteroidal anti-inflammatory drugs (NSAIDs) in management of both postoperative inflammation and cystoid macular edema. Prospective data from Europe supports the efficacy of intracameral cephalosporins in reducing the incidence of endophthalmitis. We compare this with retrospective data from the United States describing a low incidence of endophthalmitis when using fourth-generation fluoroquinolones as chemoprophylaxis. Other studies demonstrate the anti-inflammatory effect of multiple perioperative topical NSAIDs. Further important questions remain, however, including whether NSAIDs exhibit a superior side-effect profile relative to corticosteroids, whether benefit exists to combination NSAID/corticosteroid therapy, as well as whether NSAIDS can reduce the incidence of cystoid macular edema.
SUMMARY: New evidence clarifies the use of intracameral antibiotics, and other studies support a niche anti-inflammatory role for NSAIDs.
PMID: 18090893 [PubMed - in process]
The role of NSAIDs in the management of postoperative ophthalmic inflammation.
Drugs. 2007
University Hospital Complex of Bordeaux, Peflegrin Hospital, Bordeaux, France. joseph.colin@chu-bordeaux.fr
Recent advances in cataract surgery, such as phacoemulsification, small-incision surgery and advances in foldable intraocular lenses, have resulted in the decrease of physical trauma associated with cataract surgery. The decrease in the physical surgical trauma decreases the release of prostaglandins, which are the main players in postoperative ocular inflammation. However, postoperative inflammation continues to be a cause of patient discomfort, delayed recovery and, in some cases, suboptimal visual results. Left untreated, this inflammation might interfere with patients' rehabilitation and/or contribute to the development of other complications, such as cystoid macular oedema.NSAIDs are commercially available, in topical or systemic formulations, for the prophylaxis and treatment of ocular conditions. Topically applied NSAIDs are commonly used in the management and prevention of non-infectious ocular inflammation and cystoid macular oedema following cataract surgery. They are also used in the management of pain following refractive surgery and in the treatment of allergic conjunctivitis. Despite their chemical heterogeneity, all NSAIDs share the similar therapeutic property of inhibiting the cyclo-oxygenase enzyme. The appeal of using NSAIDs in the treatment of ocular inflammation hinges on the complications associated with corticosteroids, the other commonly used therapy for ophthalmic inflammation.
PMID: 17547472 [PubMed - indexed for MEDLINE]
Saturday, December 15, 2007
Carbapenems: a potent class of antibiotics.
Carbapenems: a potent class of antibiotics.
Expert Opin Pharmacother. 2008 Jan
Nicolau DP.
Hartford Hospital, Center for Anti-Infective Research and Development, 80 Seymour Street, Hartford, Connecticut 06102-5037, USA +1 860 545 3941 ; +1 860 545 3992 ; dnicola@harthosp.org.
The purpose of this review is to assess the relative strengths and weaknesses of individual members of the carbapenem class of antibiotics. Clinical trials and review articles were identified from a Medline search (1979 - July 2006), in addition to, reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and the 12th International Congress on Infectious Disease, and package inserts. Articles in English were reviewed, with emphasis on those containing efficacy or safety data. Carbapenems bind to critical penicillin-binding proteins, disrupting the growth and structural integrity of bacterial cell walls. They provide enhanced anaerobic and Gram-negative coverage as compared with other beta-lactams and their stability against extended-spectrum beta-lactamases (ESBLs) makes them an effective treatment option. The most common adverse effects are infusion-site complications and gastrointestinal distress.
Ertapenem has limited efficacy against non-fermenting, Gram-negative bacteria, restricting its use to community-acquired infections. Imipenem is slightly more effective against Gram-positive organisms and meropenem slightly more effective against Gram-negative organisms. However, both have broad-spectrum activity, including non-fermenting, Gram-negative bacteria. Among non-fermenting, Gram-negatives, resistance to imipenem in particular is increasing. Doripenem is in late-stage clinical development and combines the broad-spectrum coverage of imipenem and meropenem, and more potent activity against Pseudomonas aeruginosa. Due to the increasing challenges represented by ESBLs and multi-drug resistant organisms, the carbapenems are assuming a greater role in the treatment of serious infections.
Imipenem and meropenem are presently available and have been shown to be effective against nosocomial infections.
Doripenem is an investigational carbapenem that has completed Phase III clinical trials and that has the potential to improve on this efficacy and minimize the emergence of resistance to the carbapenem class.
PMID: 18076336 [PubMed - in process]
Expert Opin Pharmacother. 2008 Jan
Nicolau DP.
Hartford Hospital, Center for Anti-Infective Research and Development, 80 Seymour Street, Hartford, Connecticut 06102-5037, USA +1 860 545 3941 ; +1 860 545 3992 ; dnicola@harthosp.org.
The purpose of this review is to assess the relative strengths and weaknesses of individual members of the carbapenem class of antibiotics. Clinical trials and review articles were identified from a Medline search (1979 - July 2006), in addition to, reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and the 12th International Congress on Infectious Disease, and package inserts. Articles in English were reviewed, with emphasis on those containing efficacy or safety data. Carbapenems bind to critical penicillin-binding proteins, disrupting the growth and structural integrity of bacterial cell walls. They provide enhanced anaerobic and Gram-negative coverage as compared with other beta-lactams and their stability against extended-spectrum beta-lactamases (ESBLs) makes them an effective treatment option. The most common adverse effects are infusion-site complications and gastrointestinal distress.
Ertapenem has limited efficacy against non-fermenting, Gram-negative bacteria, restricting its use to community-acquired infections. Imipenem is slightly more effective against Gram-positive organisms and meropenem slightly more effective against Gram-negative organisms. However, both have broad-spectrum activity, including non-fermenting, Gram-negative bacteria. Among non-fermenting, Gram-negatives, resistance to imipenem in particular is increasing. Doripenem is in late-stage clinical development and combines the broad-spectrum coverage of imipenem and meropenem, and more potent activity against Pseudomonas aeruginosa. Due to the increasing challenges represented by ESBLs and multi-drug resistant organisms, the carbapenems are assuming a greater role in the treatment of serious infections.
Imipenem and meropenem are presently available and have been shown to be effective against nosocomial infections.
Doripenem is an investigational carbapenem that has completed Phase III clinical trials and that has the potential to improve on this efficacy and minimize the emergence of resistance to the carbapenem class.
PMID: 18076336 [PubMed - in process]
Friday, November 30, 2007
National trends in emergency department antibiotic prescribing for children with acute otitis media, 1996 2005.
National trends in emergency department antibiotic prescribing for children with acute otitis media, 1996 2005.
Acad Emerg Med. 2007 Dec
Fischer T, Singer AJ, Lee C, Thode HC Jr.
Department of Emergency Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA.
OBJECTIVES: Withholding antibiotics in nontoxic children with acute otitis media (AOM) is now recommended to reduce bacterial resistance rates. Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), the authors describe the national trends for prescribing antibiotics in children with AOM presenting to emergency departments (EDs) in the United States over the past decade. The authors hypothesized that the rates of prescribing antibiotics would decline over time.
METHODS: This was a retrospective study of NHAMCS databases. A national sampling of ED visits for 1996-2005 was used to identify trends in ED prescription of antibiotics to patients with AOM. The National Drug Code Directory Drug Classes were used to identify type of antibiotic prescribed. Frequency and type of antibiotic prescription patterns over time were evaluated.
RESULTS: There were 2.6 million and 2.1 million ED visits for AOM during the first and last years of the study. Children ages 2-12 years accounted for about 40% of all ED visits for AOM, with another 40% in the younger than 2 years age group and 20% in the older than 12 years of age group. During the first and last year of the study, 79.2% and 91.3% of the patients with AOM were prescribed antibiotics, respectively. There was a slight increasing trend in the proportion prescribed antibiotics over time (p = 0.02). The rates of use of antibiotics for AOM were similar in all three age groups.
CONCLUSIONS: There was a slight increase in the percentage of children with AOM who were prescribed antibiotics in the ED between 1996 and 2005. There was also no change in the patterns of prescribing antibiotics.
Acad Emerg Med. 2007 Dec
Fischer T, Singer AJ, Lee C, Thode HC Jr.
Department of Emergency Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA.
OBJECTIVES: Withholding antibiotics in nontoxic children with acute otitis media (AOM) is now recommended to reduce bacterial resistance rates. Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), the authors describe the national trends for prescribing antibiotics in children with AOM presenting to emergency departments (EDs) in the United States over the past decade. The authors hypothesized that the rates of prescribing antibiotics would decline over time.
METHODS: This was a retrospective study of NHAMCS databases. A national sampling of ED visits for 1996-2005 was used to identify trends in ED prescription of antibiotics to patients with AOM. The National Drug Code Directory Drug Classes were used to identify type of antibiotic prescribed. Frequency and type of antibiotic prescription patterns over time were evaluated.
RESULTS: There were 2.6 million and 2.1 million ED visits for AOM during the first and last years of the study. Children ages 2-12 years accounted for about 40% of all ED visits for AOM, with another 40% in the younger than 2 years age group and 20% in the older than 12 years of age group. During the first and last year of the study, 79.2% and 91.3% of the patients with AOM were prescribed antibiotics, respectively. There was a slight increasing trend in the proportion prescribed antibiotics over time (p = 0.02). The rates of use of antibiotics for AOM were similar in all three age groups.
CONCLUSIONS: There was a slight increase in the percentage of children with AOM who were prescribed antibiotics in the ED between 1996 and 2005. There was also no change in the patterns of prescribing antibiotics.
PMID: 18045893 [PubMed - in process]
Thursday, November 22, 2007
Speed of bacterial kill with a fluoroquinolone compared with nonfluoroquinolones: clinical implications and a review of kinetics of kill studies.
Speed of bacterial kill with a fluoroquinolone compared with nonfluoroquinolones: clinical implications and a review of kinetics of kill studies.
Adv Ther. 2007 Sep-Oct
Lichtenstein SJ, Wagner RS, Jamison T, Bell B, Stroman DW.
Associate Clinical Professor of Pediatrics and Surgery, University of Illinois College of Medicine at Peoria and Chicago, Illinois Eye Center, Peoria, Illinois.
It is important to rapidly eradicate bacteria in patients with bacterial conjunctivitis in order to decrease disease transmission, shorten symptom duration, and minimize the emergence of resistant bacteria. This paper presents the results of kinetics of kill studies on 3 commonly isolated pathogens in bacterial conjunctivitis.
A more rapid speed of kill with moxifloxacin compared with other nonfluoroquinolone antibiotics (tobramycin, gentamicin, polymyxin B/trimethoprim, or azithromycin) was observed in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae infections. Moxifloxacin achieved a 99.9% kill at approximately 1 h for S aureus, 2 h for S pneumoniae, and 30 min for H influenzae.
In comparison, other nonfluoroquinolone therapies took longer to achieve a bactericidal (3-log) kill and some demonstrated no change or an increase in bacterial growth. Based on these findings, it is concluded that moxifloxacin kills bacteria more rapidly than nonfluoroquinolone topical ocular antibiotics.
PMID: 18029337 [PubMed - in process]
Adv Ther. 2007 Sep-Oct
Lichtenstein SJ, Wagner RS, Jamison T, Bell B, Stroman DW.
Associate Clinical Professor of Pediatrics and Surgery, University of Illinois College of Medicine at Peoria and Chicago, Illinois Eye Center, Peoria, Illinois.
It is important to rapidly eradicate bacteria in patients with bacterial conjunctivitis in order to decrease disease transmission, shorten symptom duration, and minimize the emergence of resistant bacteria. This paper presents the results of kinetics of kill studies on 3 commonly isolated pathogens in bacterial conjunctivitis.
A more rapid speed of kill with moxifloxacin compared with other nonfluoroquinolone antibiotics (tobramycin, gentamicin, polymyxin B/trimethoprim, or azithromycin) was observed in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae infections. Moxifloxacin achieved a 99.9% kill at approximately 1 h for S aureus, 2 h for S pneumoniae, and 30 min for H influenzae.
In comparison, other nonfluoroquinolone therapies took longer to achieve a bactericidal (3-log) kill and some demonstrated no change or an increase in bacterial growth. Based on these findings, it is concluded that moxifloxacin kills bacteria more rapidly than nonfluoroquinolone topical ocular antibiotics.
PMID: 18029337 [PubMed - in process]
Thursday, November 15, 2007
Telavancin: A novel lipoglycopeptide antimicrobial agent.
Telavancin: A novel lipoglycopeptide antimicrobial agent
Ryan J. Attwood and Kerry L. LaPlante
RYAN J. ATTWOOD, PHARM.D., is Postgraduate Year 1 Pharmacy Resident, Henry Ford Hospital, Detroit, MI; at the time of writing he was Pharm.D. degree candidate, University of Rhode Island, Providence. KERRY L. LAPLANTE, PHARM.D., is Assistant Professor of Pharmacy, Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center, Providence.
Address correspondence to Dr. LaPlante at the Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center (151), Research Building, 830 Chalkstone Avenue, Providence, RI 02908 (kerrytedesco@uri.edu
Purpose.
The pharmacology, activity, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and place in therapy of telavancin are reviewed.
Summary.
Telavancin is a lipoglycopeptide antimicrobial agent under development for use in the treatment of multidrug-resistant gram-positive infections. Telavancin, like vancomycin, inhibits cell-wall biosynthesis by binding to late-stage cell-wall precursors. However, unlike vancomycin, telavancin also depolarizes the bacterial cell membrane and disrupts its functional integrity.
Telavancin has concentration-dependent bactericidal activity and is active against gram-positive aerobic and anaerobic organisms. It is highly protein bound (93%) and has a volume of distribution of 115 mL/kg and a half-life of approximately eight hours. Telavancin is eliminated renally, and a dosage reduction is required in renally impaired patients. Animal models suggest that telavancin may be effective in the treatment of soft-tissue infections, bacteremia, endocarditis, meningitis, and pneumonia caused by gram-positive pathogens. Telavancin was not inferior to standard treatment for complicated skin and soft-tissue infections in two Phase II clinical trials and two Phase III clinical trials.
A new drug application has been submitted for this indication, and Phase III trials to evaluate use in hospital-acquired-pneumonia, including infections caused by methicillin-resistant Staphylococcus aureus (MRSA), are planned. Adverse effects include metallic taste, nausea, vomiting, headache, foamy urine, Q-Tc-interval prolongation, hypokalemia, and serum creatinine increases. In trials evaluating telavancin for skin and soft-tissue infections, the dosage was 10 mg/kg i.v. once daily.
Conclusion.
Telavancin is a promising new agent for gram-positive infections and may offer an alternative to vancomycin for MRSA-associated infections.
American Journal of Health-System Pharmacy
Ryan J. Attwood and Kerry L. LaPlante
RYAN J. ATTWOOD, PHARM.D., is Postgraduate Year 1 Pharmacy Resident, Henry Ford Hospital, Detroit, MI; at the time of writing he was Pharm.D. degree candidate, University of Rhode Island, Providence. KERRY L. LAPLANTE, PHARM.D., is Assistant Professor of Pharmacy, Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center, Providence.
Address correspondence to Dr. LaPlante at the Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center (151), Research Building, 830 Chalkstone Avenue, Providence, RI 02908 (kerrytedesco@uri.edu
Purpose.
The pharmacology, activity, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and place in therapy of telavancin are reviewed.
Summary.
Telavancin is a lipoglycopeptide antimicrobial agent under development for use in the treatment of multidrug-resistant gram-positive infections. Telavancin, like vancomycin, inhibits cell-wall biosynthesis by binding to late-stage cell-wall precursors. However, unlike vancomycin, telavancin also depolarizes the bacterial cell membrane and disrupts its functional integrity.
Telavancin has concentration-dependent bactericidal activity and is active against gram-positive aerobic and anaerobic organisms. It is highly protein bound (93%) and has a volume of distribution of 115 mL/kg and a half-life of approximately eight hours. Telavancin is eliminated renally, and a dosage reduction is required in renally impaired patients. Animal models suggest that telavancin may be effective in the treatment of soft-tissue infections, bacteremia, endocarditis, meningitis, and pneumonia caused by gram-positive pathogens. Telavancin was not inferior to standard treatment for complicated skin and soft-tissue infections in two Phase II clinical trials and two Phase III clinical trials.
A new drug application has been submitted for this indication, and Phase III trials to evaluate use in hospital-acquired-pneumonia, including infections caused by methicillin-resistant Staphylococcus aureus (MRSA), are planned. Adverse effects include metallic taste, nausea, vomiting, headache, foamy urine, Q-Tc-interval prolongation, hypokalemia, and serum creatinine increases. In trials evaluating telavancin for skin and soft-tissue infections, the dosage was 10 mg/kg i.v. once daily.
Conclusion.
Telavancin is a promising new agent for gram-positive infections and may offer an alternative to vancomycin for MRSA-associated infections.
American Journal of Health-System Pharmacy
Saturday, November 10, 2007
Daptomycin in the Treatment of Bacteremia
Daptomycin in the Treatment of Bacteremia
George Sakoulas MDa, Yoav Golan MD, MSb, Kenneth C. Lamp PharmDc, , , Lawrence V. Friedrich PharmDc and Rene Russo PharmDc aNew York Medical College, Valhalla, New York, USAbTufts New England Medical Center, Boston, Massachusetts, USAcCubist Pharmaceuticals, Inc., Lexington, Massachusetts, USA. Available online 28 September 2007.
George Sakoulas MDa, Yoav Golan MD, MSb, Kenneth C. Lamp PharmDc, , , Lawrence V. Friedrich PharmDc and Rene Russo PharmDc aNew York Medical College, Valhalla, New York, USAbTufts New England Medical Center, Boston, Massachusetts, USAcCubist Pharmaceuticals, Inc., Lexington, Massachusetts, USA. Available online 28 September 2007.
Abstract
The aim of this study was to describe the clinical experience with daptomycin in the treatment of bacteremia. Patients with a diagnosis of catheter-related or non–catheter-related bacteremia and no other concurrent infection were identified from the Cubicin Outcomes Registry and Experience (CORE) 2004. Treatment success was determined by investigators using protocol criteria and defined as cure or improvement. Of 168 patients with bacteremia, 126 were clinically evaluable. Of those, 52 (41%) patients were aged ≥66 years, 54 (43%) received daptomycin in an intensive care unit, and 25 (20%) had chronic renal failure. The most common pathogens isolated were methicillin-resistant Staphylococcus aureus (33%), vancomycin-resistant enterococci (30%), and coagulase-negative staphylococci (30%). Of 126 patients, 86% received daptomycin after previous antibiotic therapy and most (69%) received concomitant antibiotics with daptomycin. Daptomycin therapy was started at a median dose of 4.0 mg/kg (range, 2.5 to 9.2 mg/kg). Daptomycin therapy had an overall clinical success rate of 89%. Clinical success was independent of baseline renal function, daptomycin dose, pathogen, first-line use, or concomitant antibiotic therapy. These results support the findings of a recent study in which daptomycin was demonstrated to be an effective option in the treatment of S aureus bacteremia. Data in the current study provide insight into the clinical experience using daptomycin to treat bacteremia caused by other gram-positive pathogens. Given the limitations of retrospective studies and lack of follow-up data, additional studies are needed to make definitive evaluations with these pathogens.
Science Direct
Wednesday, November 07, 2007
Goniothalamus species: a source of drugs for the treatment of cancers and bacterial infections?
Goniothalamus species: a source of drugs for the treatment of cancers and bacterial infections?
Evid Based Complement Alternat Med. 2007 Sep
Evidence-based Complementary and Alternative Medicine
Evid Based Complement Alternat Med. 2007 Sep
Wiart C.
School of Pharmacy, The University of Nottingham (Malaysia Campus), Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
Keywords: acetogenins, antibacterial, antifungal, apoptosis, cytotoxic, foodborn bacteria, Goniothalamus, Goniothalamus scortechinii, nosocomial, styryl-lactones.
Irrespective of the presence of cytotoxic acetogenins and styryl-lactones in the genus Goniothalamus, only 22 species in the genus Goniothalamus, out of 160 species (13.7%) have so far been investigated. In an effort to promote further research on the genus Goniothalamus which could represent a source of drugs for the treatment of cancers and bacterial infections, this work offers a broad analysis of current knowledge on Goniothalamus species. Therefore, it includes (i) taxonomy (ii) botanical description (iii) traditional medicinal uses and (iv) phytochemical and pharmacological studies. We discuss the molecular mechanisms of actions of acetogenins and styryl-lactones, with some emphasis on the possible involvement of protein kinase, Bax and TRAIL receptors in the cytotoxic effects of styryl-lactones. We also report (v) the growth inhibition of several nosocomial bacteria by Goniothalamus. scortechinii. The crude methanol extract of G. scortechinii showed a good and broad spectrum of antibacterial activity against both Gram-negative and Gram-positive bacteria.
Full Text ArticleEvidence-based Complementary and Alternative Medicine
Biodegradable gentamicin delivery systems for parenteral use for the treatment of intracellular bacterial infections
Biodegradable gentamicin delivery systems for parenteral use for the treatment of intracellular bacterial infections
November 2007, Vol. 4, No. 6, Pages 677-688
(doi:10.1517/17425247.4.6.677)
1University of Navarra, Department of Microbiology, 31080 Pamplona, Spain +34 948 425 688; +34 948 425 649; cgamazo@unav.es
2Clínica Universitaria, Department of Clinical Pharmacology, 31080 Pamplona, Spain
3University of Navarra, Department of Pharmacy and Pharmaceutical Technology, 31080 Pamplona, Spain
† Author for correspondence
Gentamicin is an aminoglycoside with a wide spectrum of antibacterial activity. However, as a highly water-soluble drug, it penetrates cells poorly. This constitutes a particularly important drawback for treating intracellular bacterial infections. This major hurdle may be solved by the use of vectors to deliver and target bioactive agents to the intracellular sites of infection. Thus, in the case of antimicrobials, drug delivery systems may help to increase their therapeutic index in intracellular locations. The development and evolution of pharmaceutical forms of gentamicin for the parenteral treatment of intracellular pathogens is reviewed in this paper.
Expert Opinion
Subscribe to:
Posts (Atom)