Colistin is Effective in the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections in Cancer Patients.
Antimicrob Agents Chemother. 2007 Mar 26
Hachem RY,
Chemaly RF,
Ahmar CA,
Jiang Y,
Boktour MR,
Rjaili GA,
Bodey GP,
Raad II.
The University of Texas M. D. Anderson Cancer Center, Department of Infectious Diseases, Houston, Texas, and Staten Island University Hospital, Staten Island, New York.
Background: The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new anti-pseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism.
Methods: We collected clinical and demographic data on 95 cancer patients diagnosed with multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active anti-pseudomonal agent (a beta-lactam antibiotic or quinolone) (control group). We compared both groups.
Results: Thirty-one patients had been treated with colistin and 64 had been treated with an anti-pseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had lower median age (52 vs 62 years; P = 0.012), but more likely to have had nosocomial infections (87% vs 64%; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). Overall clinical response rate was 52% in the colistin group versus 31% in the non-colistin group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% CI: 1.1 to 7.6) more likely to experience a clinical response to therapy than were those in the control group (P = 0.026).
Conclusions: Colistin therapy was at least as effective and as safe as beta-lactam antibiotics and quinolones in the treatment of multidrug-resistant P. aeruginosa infections and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.
Antimicrobial Agents and Chemotherapy Online
Friday, March 30, 2007
Thursday, March 22, 2007
Will The Plague Pathogen Become Resistant To Antibiotics?
Will The Plague Pathogen Become Resistant To Antibiotics?
Mar 21 2007
Science Daily — A small piece of DNA that helps bacteria commonly found in US meat and poultry resist several antibiotics has also been found in the plague bacillus Yersinia pestis, gene sequence researchers report.
The ability to resist many of the antibiotics used against plague has been found so far in only a single case of the disease in Madagascar. But because the same ability is present in other kinds of bacteria from a broad range of livestock, antibiotic resistance could potentially spread to other Y. pestis and also other bacterial pathogens. In a paper published March 21 in the new journal PLoS ONE, the authors say this possibility "represents a significant public health concern."
Genetic ability to disable antibiotics, including multidrug resistance (MDR) sequences, is carried on plasmids, small circles of DNA that are passed easily between bacteria. In this study, the same MDR plasmids found in the Y. pestis from Madagascar were also present in bacteria such as Salmonella and Escherichia coli found in retail samples of beef, pork, chicken, and turkey from several US states.
"What we've done is revealed a mechanism for the acquisition of multidrug resistance in Y. pestis. Obviously, this is an event that might have serious human health consequences. But the sequencing work we've done has given us a way to monitor this plasmid in future," says senior author Jacques Ravel of The Institute for Genomic Research (TIGR) in Rockville, MD.
"The fact that we found a plasmid usually found in Salmonella in Y. pestis is a big problem. It also raises a question about how this happened, how it went from one to the other. But that's a question we cannot answer in this paper," Ravel notes. He urges a new monitoring program to track MDR in Y. pestis.
MDR Salmonella and E. coli have been found in droppings from wild geese, raising the possibility that wild animals might be able to spread MDR far beyond the livestock where it originated, Ravel notes.
"When we identified the first Y. pestis strain resistant to multiple antibiotics, we warned that if this type of strain spreads or emerges again, it would pose a serious health problem" says co-author Elisabeth Carniel, head of the Yersinia Research Unit at the Institut Pasteur in Paris. "The discovery that the multiresistance plasmid acquired by the plague bacillus is widespread in environmental bacteria reinforces this warning".
There have been many plague epidemics in human history, and Y. pestis is believed to have killed an estimated 200 million people. Plague is now regarded as a re-emerging disease, with small outbreaks all over the world. Because plague is often fatal, Y. pestis is a potential agent for bioterrorism. There is no vaccine, but antibiotics are useful for treatment and for preventing the disease's spread. The researchers observe, "Our data imply that high levels of MDR in the causative agent of plague may rapidly evolve naturally, and present a vital biomedical, public health, and biodefense threat."
The paper resulted from an international collaboration among researchers at TIGR, a division of the J. Craig Venter Institute, the Institut Pasteur in Paris, the Agricultural Research Service of the US Department of Agriculture, and the US Food and Drug Administration. This work was performed at the National Institute of Allergy and Infectious Diseases-funded Microbial Sequencing Center managed by TIGR.
Citation: Welch TJ, Fricke WF, McDermott PF, White DG, Rosso M, et al (2007) Multiple Antimicrobial Resistance in Plague: An Emerging Public Health Risk. PLoS ONE 2(3): e309. doi:10.1371/journal.pone.0000309
Science Daily
Mar 21 2007
Science Daily — A small piece of DNA that helps bacteria commonly found in US meat and poultry resist several antibiotics has also been found in the plague bacillus Yersinia pestis, gene sequence researchers report.
The ability to resist many of the antibiotics used against plague has been found so far in only a single case of the disease in Madagascar. But because the same ability is present in other kinds of bacteria from a broad range of livestock, antibiotic resistance could potentially spread to other Y. pestis and also other bacterial pathogens. In a paper published March 21 in the new journal PLoS ONE, the authors say this possibility "represents a significant public health concern."
Genetic ability to disable antibiotics, including multidrug resistance (MDR) sequences, is carried on plasmids, small circles of DNA that are passed easily between bacteria. In this study, the same MDR plasmids found in the Y. pestis from Madagascar were also present in bacteria such as Salmonella and Escherichia coli found in retail samples of beef, pork, chicken, and turkey from several US states.
"What we've done is revealed a mechanism for the acquisition of multidrug resistance in Y. pestis. Obviously, this is an event that might have serious human health consequences. But the sequencing work we've done has given us a way to monitor this plasmid in future," says senior author Jacques Ravel of The Institute for Genomic Research (TIGR) in Rockville, MD.
"The fact that we found a plasmid usually found in Salmonella in Y. pestis is a big problem. It also raises a question about how this happened, how it went from one to the other. But that's a question we cannot answer in this paper," Ravel notes. He urges a new monitoring program to track MDR in Y. pestis.
MDR Salmonella and E. coli have been found in droppings from wild geese, raising the possibility that wild animals might be able to spread MDR far beyond the livestock where it originated, Ravel notes.
"When we identified the first Y. pestis strain resistant to multiple antibiotics, we warned that if this type of strain spreads or emerges again, it would pose a serious health problem" says co-author Elisabeth Carniel, head of the Yersinia Research Unit at the Institut Pasteur in Paris. "The discovery that the multiresistance plasmid acquired by the plague bacillus is widespread in environmental bacteria reinforces this warning".
There have been many plague epidemics in human history, and Y. pestis is believed to have killed an estimated 200 million people. Plague is now regarded as a re-emerging disease, with small outbreaks all over the world. Because plague is often fatal, Y. pestis is a potential agent for bioterrorism. There is no vaccine, but antibiotics are useful for treatment and for preventing the disease's spread. The researchers observe, "Our data imply that high levels of MDR in the causative agent of plague may rapidly evolve naturally, and present a vital biomedical, public health, and biodefense threat."
The paper resulted from an international collaboration among researchers at TIGR, a division of the J. Craig Venter Institute, the Institut Pasteur in Paris, the Agricultural Research Service of the US Department of Agriculture, and the US Food and Drug Administration. This work was performed at the National Institute of Allergy and Infectious Diseases-funded Microbial Sequencing Center managed by TIGR.
Citation: Welch TJ, Fricke WF, McDermott PF, White DG, Rosso M, et al (2007) Multiple Antimicrobial Resistance in Plague: An Emerging Public Health Risk. PLoS ONE 2(3): e309. doi:10.1371/journal.pone.0000309
Science Daily
Wednesday, March 21, 2007
Prevention of Brain Injury by Daptomycin in Experimental Pneumococcal Meningitis.
Prevention of Brain Injury by the Non Bacteriolytic Antibiotic Daptomycin in Experimental Pneumococcal Meningitis.
Antimicrob Agents Chemother. 2007 Mar 19
Grandgirard D,
Schurch C,
Cottagnoud P,
Leib SL.
Institute for Infectious Diseases, University of Bern, Switzerland, Department of Internal Medicine; and Clinic for Infectious Diseases, University Hospital, Inselspital, Bern, Switzerland.
Background: Bacteriolytic antibiotics cause the release of bacterial components that augment the host inflammatory response which in turn contributes to the pathophysiology of brain injury in bacterial meningitis. In the present study in experimental pneumococcal meningitis, antibiotic therapy with non-bacteriolytic daptomycin vs. bacteriolytic ceftriaxone was evaluated for an effect on inflammation and brain injury.
Methods: Eleven day old rats were injected intracisternally with 1.3 +/- 0.5 x 10(4) colony forming units (cfu) of Streptococcus pneumoniae serotype 3 and randomized for therapy with ceftriaxone (100 mg/kg s.c., n=55) or daptomycin (50 mg/kg s.c., n=56) starting at 18 h after infection. Cerebrospinal fluid was assessed for bacterial count, matrix metalloprotease-9 and TNF-alpha at different time intervals after infection. Cortical brain damage was evaluated at 40 h after infection.
Results: Daptomycin vs. ceftriaxone cleared bacteria more efficiently from the CSF within two hours after initiation of therapy (log10 3.6+/-1.0 vs. log10 6.3+/-1.4 cfu/ml, P<0.02),>
Conclusion: Compared to ceftriaxone, daptomycin cleared bacteria more rapidly from the CSF and caused less CSF inflammation. This combined effect provides an explanation for the observation that daptomycin prevented the development of cortical brain injury in experimental pneumococcal meningitis.
Further research is needed to investigate whether non-bacteriolytic antibiotic therapy with Daptomycin represents an advantageous alternative over current bacteriolytic antibiotics for the therapy of pneumococcal meningitis.
PMID: 17371820 [PubMed - as supplied by publisher]
Antimicrob Agents Chemother. 2007 Mar 19
Grandgirard D,
Schurch C,
Cottagnoud P,
Leib SL.
Institute for Infectious Diseases, University of Bern, Switzerland, Department of Internal Medicine; and Clinic for Infectious Diseases, University Hospital, Inselspital, Bern, Switzerland.
Background: Bacteriolytic antibiotics cause the release of bacterial components that augment the host inflammatory response which in turn contributes to the pathophysiology of brain injury in bacterial meningitis. In the present study in experimental pneumococcal meningitis, antibiotic therapy with non-bacteriolytic daptomycin vs. bacteriolytic ceftriaxone was evaluated for an effect on inflammation and brain injury.
Methods: Eleven day old rats were injected intracisternally with 1.3 +/- 0.5 x 10(4) colony forming units (cfu) of Streptococcus pneumoniae serotype 3 and randomized for therapy with ceftriaxone (100 mg/kg s.c., n=55) or daptomycin (50 mg/kg s.c., n=56) starting at 18 h after infection. Cerebrospinal fluid was assessed for bacterial count, matrix metalloprotease-9 and TNF-alpha at different time intervals after infection. Cortical brain damage was evaluated at 40 h after infection.
Results: Daptomycin vs. ceftriaxone cleared bacteria more efficiently from the CSF within two hours after initiation of therapy (log10 3.6+/-1.0 vs. log10 6.3+/-1.4 cfu/ml, P<0.02),>
Conclusion: Compared to ceftriaxone, daptomycin cleared bacteria more rapidly from the CSF and caused less CSF inflammation. This combined effect provides an explanation for the observation that daptomycin prevented the development of cortical brain injury in experimental pneumococcal meningitis.
Further research is needed to investigate whether non-bacteriolytic antibiotic therapy with Daptomycin represents an advantageous alternative over current bacteriolytic antibiotics for the therapy of pneumococcal meningitis.
PMID: 17371820 [PubMed - as supplied by publisher]
Monday, March 19, 2007
Amikacin-induced nephropathy: is there any protective way?
Amikacin-induced nephropathy: is there any protective way?
Ren Fail. 2007
Kaynar K,
Gul S,
Ersoz S,
Ozdemir F,
Ulusoy H,
Ulusoy S.
Department of Nephrology, School of Medicine, Karadeniz Technical University.
Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally).
Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment.
The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects.
Meta Press
Ren Fail. 2007
Kaynar K,
Gul S,
Ersoz S,
Ozdemir F,
Ulusoy H,
Ulusoy S.
Department of Nephrology, School of Medicine, Karadeniz Technical University.
Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally).
Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment.
The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects.
Meta Press
Tuesday, March 13, 2007
Gentamicin-loaded bioresorbable films for prevention of bacterial infections associated with orthopedic implants.
Gentamicin-loaded bioresorbable films for prevention of bacterial infections associated with orthopedic implants.
J Biomed Mater Res A. 2007 Mar 5
Aviv M,
Berdicevsky I,
Zilberman M.
Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
Adhesion of bacteria to biomaterials and the ability of many microorganisms to form biofilms on foreign bodies are well-established as major contributors to the pathogenesis of implant-associated infections. Treatment of bone infection remains problematic, due to the difficulty of systemically administered antibiotics to locally penetrate bone. The current research addresses this issue by focusing on the development and study of novel gentamicin-loaded bioresorbable films designed to serve as "coatings" for fracture fixation devices and prevent implant-associated infections.
Poly(L-lactic acid) and poly (D,L-lactic-co-glycolic acid) films containing gentamicin were developed through solution processing. The effects of polymer type, drug content, and processing conditions on the drug release profile were studied with respect to film morphology. The examined films generally exhibited a burst effect followed by a moderate approximately constant rate of release. The drug contents in the surrounding medium exceeded the required minimal effective concentration.
Various gentamicin concentrations that were released from the films with time exhibited efficacy against bacterial species known to be involved in orthopedic infections. The developed systems can be applied on the surface of any metallic or polymeric fracture fixation device, and may therefore comprise a significant contribution to the field of orthopedic implants.
Keywords:
bioresorbable films • poly(lactic acid) • poly(D,L-lactic-co-glycolic acid) • gentamicin • controlled drug delivery
2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007.
J Biomed Mater Res A. 2007 Mar 5
Aviv M,
Berdicevsky I,
Zilberman M.
Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
Adhesion of bacteria to biomaterials and the ability of many microorganisms to form biofilms on foreign bodies are well-established as major contributors to the pathogenesis of implant-associated infections. Treatment of bone infection remains problematic, due to the difficulty of systemically administered antibiotics to locally penetrate bone. The current research addresses this issue by focusing on the development and study of novel gentamicin-loaded bioresorbable films designed to serve as "coatings" for fracture fixation devices and prevent implant-associated infections.
Poly(L-lactic acid) and poly (D,L-lactic-co-glycolic acid) films containing gentamicin were developed through solution processing. The effects of polymer type, drug content, and processing conditions on the drug release profile were studied with respect to film morphology. The examined films generally exhibited a burst effect followed by a moderate approximately constant rate of release. The drug contents in the surrounding medium exceeded the required minimal effective concentration.
Various gentamicin concentrations that were released from the films with time exhibited efficacy against bacterial species known to be involved in orthopedic infections. The developed systems can be applied on the surface of any metallic or polymeric fracture fixation device, and may therefore comprise a significant contribution to the field of orthopedic implants.
Keywords:
bioresorbable films • poly(lactic acid) • poly(D,L-lactic-co-glycolic acid) • gentamicin • controlled drug delivery
2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007.
Tuesday, March 06, 2007
Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.
Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.
J Antimicrob Chemother. 2007 Mar 2;
Musher DM,
Logan N,
Mehendiratta V,
Melgarejo NA,
Garud S,
Hamill RJ.
Medical Service (Infectious Disease Section), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
Objectives Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. Methods In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >/=14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. Results Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). Conclusions Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.
PMID: 17337513 [PubMed - as supplied by publisher]
J Antimicrob Chemother. 2007 Mar 2;
Musher DM,
Logan N,
Mehendiratta V,
Melgarejo NA,
Garud S,
Hamill RJ.
Medical Service (Infectious Disease Section), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
Objectives Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. Methods In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >/=14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. Results Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). Conclusions Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.
PMID: 17337513 [PubMed - as supplied by publisher]
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