There are serious problems concerning the inadequate prescription of antibiotics and overuse of injections in primary care. However, the determinants of prescription patterns in Korea are not well-documented. To examine the area characteristics affecting the prescription of antibiotics and injections in primary care practices in the treatment of respiratory tract infections (RTIs), a nationwide cross-sectional study was performed in all 250 administrative districts of Korea. The outcome was modeled as a binary variable: over-prescription or not compared with the nation-wide average. Over-prescription of antibiotics was associated with the ratio of specialists to general physicians and over-prescription in previous years in the area (adjusted odds ratio [aOR], 4.8; 95% confidence interval [CI] 1.5-14.8; and aOR, 12.0; 95% CI 5.5-25.9, respectively). Over-use of injections was associated with younger population, urban living and the number of hospital beds in the area (aOR, 0.2; 95% CI 0.1-0.4; aOR, 0.3; 95% CI 0.1-0.8; and aOR, 0.4, 95% CI 0.2-0.9; respectively). There were differences in the prescribing patterns in different districts; prescription patterns were affected more by supply factors than by demand factors. Highly competitive medical environment associated with supply factors is a significant determinant of prescription patterns in Korea.
Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.
To investigate the role of prophylactic antibiotics in the reduction of mortality of severe acute pancreatitis (SAP) patients, which is highly questioned by more and more randomized controlled trials (RCTs) and meta-analyses.
An updated meta-analysis was performed. RCTs comparing prophylactic antibiotics for SAP with control or placebo were included for meta-analysis. The mortality outcomes were pooled for estimation, and re-pooled estimation was performed by the sensitivity analysis of an ideal large-scale RCT.
Currently available 11 RCTs were included. Subgroup analysis showed that there was significant reduction of mortality rate in the period before 2000, while no significant reduction in the period from 2000 [Risk Ratio, (RR) = 1.01, P = 0.98]. Funnel plot indicated that there might be apparent publication bias in the period before 2000. Sensitivity analysis showed that the RR of mortality rate ranged from 0.77 to 1.00 with a relatively narrow confidence interval (P < 0.05). However, the number needed to treat having a minor lower limit of the range (7-5096 patients) implied that certain SAP patients could still potentially prevent death by antibiotic prophylaxis.
Current evidences do not support prophylactic antibiotics as a routine treatment for SAP, but the potentially benefited sub-population requires further investigations.
Princeton University, Department of Molecular Biology Princeton, NJ 08544.
It has recently been suggested that bactericidal antibiotics including aminoglycosides (AGAs), and toxic small molecules, such as hydroxyurea (HU), kill bacteria the same way; namely, by generating reactive oxygen species (ROS) via a process requiring activation of the Cpx stress response. We suggest an opposite, protective role for Cpx. We have confirmed the initial finding that cpxA null mutations confer resistance to HU. However, the two-component sensor CpxA is both a kinase and a phosphatase, and previous work from our lab has shown that removing CpxA can activate the stress response owing to buildup of the phosphorylated response regulator (CpxR∼P) that occurs in the absence of the phosphatase activity. We show that a dominant cpxA* mutation that constitutively activates the Cpx stress response confers a high level of resistance to both HU and AGAs in a CpxR dependent manner. In contrast, inactivating the CpxR response regulator, by mutating the phosphorylation site (D51A) or the putative DNA-binding motif (M199A) does not increase resistance to HU or AGAs. Taken together, these results demonstrate that activation of the Cpx stress response can protect cells from HU and AGAs. However the Cpx response does not increase resistance to all classes of bactericidal antibiotics, as the cpxA* mutants are not significantly more resistant to fluoroquinolones or β-lactams than wild-type cells. Thus, it seems unlikely that all bactericidalantibiotics kill by the same mechanism.
Department of Stomatology, Huashan Hospital, Fudan University, Shanghai 200040, China. Email: email@example.com.
To isolate and culture the predominant anaerobes from the periodontal abscesses, and to test the antibiotic susceptibility and drug resistant genes of the strains.
The isolated strains were identified by both API20A biochemical method and polymerase chain reaction (PCR) method. The antibiotic susceptibility test was performed by agar dilution method. The resistant genes of the drug-resistant strains obtained were screened by PCR.
The anaerobes were detected in 48% (28/58) of the samples and Prevotella melaninogenica (Pm) was mostly identified in 43% (12/28). API20A biochemical method had 82% (23/28) agreement with the 16SrRNA method in identification rate. Anaerobes were resistant to metronidazole, clindamycin and cefmetazole. The erythromycin-resistant methylase genes F (ermF) gene was detected in three of eight clindamycin resistant strains. None of them was found coded on bacterial plasmids. However, no metronidazole resistant gene was detected on drug resistant strains.
Pm was the predominant species dectected in the periodontal abscess of the patients. The antibiotic agents should be used based on the genotypes and general condition of the patients.
Beth Israel Medical Center, Newark, New Jersey , the Netherlands.
adverse drug reaction
To provide clinicians with an understandingof the comparative occurrence of tigecycline and pancreatitis, and to provide any clinically relevant characteristics that may be useful in identifying the patients at risk.
Retrospective cohort study.
Spontaneous reports in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database generated between January 1997 and December 2010.
Sixty-two patients who experienced pancreatitis while receiving tigecycline therapy.
MEASUREMENTS AND MAIN RESULTS:
Disproportionality analysis with Bayesia n correction methodology was used to compare tigecycline with all other agents listed in the AERS. Disproportionality analysis uses an adverse event relative reporting ratio (RRR) to compare the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA-approved prescription drugs. The value was considered meaningful if the 5th percentile of the distribution of the RRR (RRR(05) ) was 2 or greater. Our review identified 62 potential cases of tigecyline-related pancreatitis. An RRR(05) score of 10.4, 10.38, and 2.87 was determined for tigecycline-related pancreatitis compared with all other agents, systemic antibiotics, and select tetracyclines listed in the AERS, respectively. In addition, a sex-based RRR(05) score was higher in women versus men (14.432 vs 3.125) when tigecycline was compared with all agents in the AERS.
Our analysis suggests a quantitative signal between tigecycline use and pancreatitis; however, given the limitations of our study, a cause-and-effect relationship cannot be inferred. Thus, additional rigorous scientific analyses are warranted to explore these findings.
Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India.
Background & objectives:The resistance of bacteria causing urinary tract infection (UTI) to commonly prescribed antibiotics is increasing both in developing as well as in developed countries. Resistance has emerged even to more potent antimicrobialagents. The present study was undertaken to report the current antibiotic resistance pattern among common bacterial uropathogens isolated in a tertiary care hospital in south India, with a special reference to ciprofloxacin.
Methods: A total of 19,050 consecutive urine samples were cultured and pathogens isolated were identified by standard methods. Antibiotic susceptibility was done by Kirby Bauer disk diffusion method. The clinical and demographic profile of the patients was noted. Results: Of the 19,050 samples, 62 per cent were sterile, 26.01 per cent showed significant growth, 2.3 per cent showed insignificant growth and 9.6 per cent were found contaminated. Significant association of prior use of antibiotics in males, UTI in adults, gynecological surgery in females, obstructive uropathy in males and complicated UTI in females with the occurrence of UTI with ciprofloxacin resistant Escherichia coli was noted. Significant association was noted in females with prior antibiotics, with prior urological surgery and in males with prior complicated UTI. There was no significant association with diabetes mellitus with the occurrence of UTI with ciprofloxacin resistant E. coli. Fluoroquinolone resistance was found to increase with age.
Interpretations & conclusions:Ciprofloxacin resistance has emerged due to its frequent use. This resistance was seen more in the in-patients, elderly males and females. Also the resistance to other antibiotics was also high. Increasing antibiotic resistance trends indicate that it is imperative to rationalize the use of antimicrobials in the community and also use these conservatively.
National Reference Laboratory of Veterinary Drug Residues(HZAU)/MOA Key Laboratory of Food Safety Evaluation, Huazhong Agricultural University, Wuhan 430070, P. R. China.
Macrolide antibiotics are important for clinical treatment of infections caused by Campylobacter jejuni. Development of resistance to this class of antibiotics in Campylobacter is a complex process and the dynamic molecular changes involved in this process remain poorly defined. Multiple lineages of macrolide-resistant mutants were selected by stepwise exposure of C. jejuni to escalating doses of erythromycin or tylosin. Mutations in target genes were determined by DNA sequencing and the dynamic changes in the expression of antibiotic efflux transporters and the transcriptome of C. jejuni were examined by real-time RT-PCR, immunoblotting, and DNA microarray. Multiple types of mutations in ribosomal proteins L4 and L22 occurred in the early stepwise selection. On the contrary, the mutations in 23S rRNA gene, mediating highly resistant to macrolides, were only observed in the late-stage mutants. Upregulation of antibiotic efflux genes was observed in the intermediate-level resistant mutants, and the magnitude of upregulation declined as the occurrence of mutations in the 23S rRNA. DNA microarray analysis revealed differential expression of 265 genes, most of which occurred in the intermediate mutant, including upregulation of genes encoding ribosomal proteins and downregulation of genes involved in energy metabolism and motility. These results indicate 1) that mutations in L4 and L22 along with temporal overexpression of antibiotic efflux genes precede and may facilitate the development of high-level macrolide resistance and 2) that the development of macrolide resistance affects the pathways important for physiology and metabolism in C. jejuni, providing an explanation for the reduced fitness of macrolide-resistant Campylobacter.
Department of Antibiotics and Microbiology, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland. Electronic address: firstname.lastname@example.org.
The oxazolidinones are a new and potent class of antimicrobial agents with activity mainly against Gram-positive strains. The commercial success of linezolid, the only FDA-approved oxazolidinone, has prompted many pharmaceutical companies to devote resources to this area of investigation. Until now, four types of chemical modifications of linezolid and oxazolidinone-type antibacterial agents, including modification on each of the A-(oxazolidinone), B-(phenyl), and C-(morpholine) rings as well as the C-5 side chain of the A-ring substructure, have been described. Division into sections according to side chain modification or the type of ring will be used throughout this review, although the process of synthesis usually involves the simultaneous modification of several elements of the linezolid substructure; therefore, assignment into the appropriate section depends on the structure-activity relationships (SAR) studies. This review makes an attempt to summarise the work carried out in the period from 2006 until mid-2012.