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Mechanisms of Antibiotic Resistance in Acinetobacter spp. — Genetics of Resistance
Published in E. Bergogne-Bénézin, M.L. Joly-Guillou, K.J. Towner, Acinetobacter, 2020
It was uncertain whether a smaller number of small-sized porins from a wild-type strain could be modified further to confer increased levels of ß-lactam resistance. Obara and Nakae (1991) examined two clinical strains of Acinetobacter, strains 4751 and 4760. Strain 4751 was a ß-lactam resistant isolate, whereas strain 4760 was generally ß-lactamsensitive. Three cephalosporin-resistant mutants of strain 4760, TNA001, TNA002 and TNA003, were isolated by selection on high concentrations of cefoxitin, cefoperazone or ceftazidime, respectively. Examination of cell-free extracts revealed that the resistant clinical strain 4751 produced 77.4-fold as much C-lactamase as the sensitive clinical strain 4760 (4.8 pmol of cephalothin hydrolysed/min/mg protein compared with 62 nmol). These ß-lactamase specific activities were unaffected if the strains were pre-induced with cephaloridine, imipenem or cefoperazone. In contrast, the resistant mutants of strain 4760 did not produce significantly elevated levels of ß-lactamase, as none of the three mutants had a specific activity of >94 nmol cephalothin hydrolysed/min/mg protein, and they could not be induced. Increased ß-lactamase production was therefore not responsible for the cephalosporin resistance in the laboratory mutants, whereas this was a major factor in the resistant clinical strain.
Bacterial Meningitis
Published in Thomas T. Yoshikawa, Shobita Rajagopalan, Antibiotic Therapy for Geriatric Patients, 2005
This organism is the most frequent cause (70%) of bacterial meningitis in older adults and may be recognized as gram-positive diplococci with elongation or lancet-shaped morphology (4). Over 85 serotypes are identified with some known to more frequently cause severe disease due to capsular and other bacterial virulence factors. Treatment of this organism is complicated by penicillin and cephalosporin resistance mediated by alterations in penicillin-binding proteins. This resistance is particularly problematic in the treatment of meningitis since CSF levels of penicillins and cephalosporins adequate enough to overcome this resistance may be difficult to achieve.
Antimicrobial Stewardship Initiatives: A Programmatic Approach to Optimizing Antimicrobial Use
Published in Robert C. Owens, Paul G. Ambrose, Charles H. Nightingale, Antibiotic Optimization, 2004
Gilles L. Fraser, Patricia Stogsdill, Robert C. Owens
Not too surprising is that the antibiotic order form and education provided by the team with regard to avoidance of third-generation cephalosporins and carbapenems and their suitable replacements (aminopenicillin/sulbactam combinations, cefepime) were effective in shifting antimicrobial use between periods I and II, and this continued throughout the study. The program periods were associated with declining cost savings as time advanced (periods II, III, and IV were associated with a reduction of $261,955, $57,245, and $12,881, respectively). Comparing antibiotic order forms from period I (voluntary form and preintervention, n = 450) with period IV (mandatory form with active intervention, n = 349) noted an increase in microbiologically based treatment intent (27% vs. 62.8%, respectively, p < 0.0001). Twenty-seven percent of the period IV antibiotic order forms were intervened upon by the team. Of the interventions, either the dose or duration (not specified) was reduced in 11.5%, 86.1% were associated with cost reduction, and 47% involved streamlining therapy to a narrower choice. In terms of impact on nosocomial infection, length of hospitalization, and mortality, only length of stay was affected significantly (p = 0.04). The increased rate of cefepime use relative to third-generation cephalosporins was associated with declining third-generation cephalosporin resistance rates among Proteus mirabilis and Enterobacter cloacae but not to E. coli or Klebsiella pneumoniae. The increased rate of aminopenicillin/sulbactam use relative to the third-generation cephalosporins in conjunction with a sustained reduction in vancomycin use was associated with a reduction in MRS A rates. In addition, P. aeruginosa resistance rates to carbapenems declined to 0%. This was strongly associated with the reduction in carbapenem consumption over time.
Bloodstream infections and antibiotic resistance patterns: a six-year surveillance study from southern Italy
Published in Pathogens and Global Health, 2023
F. Foglia, M.T. Della Rocca, C. Melardo, B.M. Nastri, M. Manfredini, F. Montella, A. De Filippis, E. Finamore, Massimiliano Galdiero
Amongst the Gram-negative bacterial pathogens, E. coli was susceptible to carbapenems and fosfomycin, but showed moderate resistance to aminoglycosides and cephalosporins. This was consistent with a previous study carried out in Italy that reported decreasing E. coli carbapenem resistance [25]. Fluoroquinolone resistance in Southern Italy is higher compared to other European countries. Moreover, the proportion of fluoroquinolone-resistant and of cephalosporins resistant E. coli and K. pneumoniae bloodstream isolates may be extremely high (>60%) in some parts of the world [26,27]. In our study, fluoroquinolone resistance was moderately high among K. pneumoniae isolates but decreased in 2021, whereas the opposite was noted for P. aeruginosa, in which resistance levels increased 5-fold between 2018 and 2021. We noted some resistance amongst Gram-negative pathogens to the second- and third-generation cephalosporins, including cefepime and cefotaxime. The emergence of cephalosporin resistance amongst E. coli and K. pneumoniae, which is primarily caused by ESBL enzymes, has changed the epidemiology of the pathogens as causes of BSI [28].
Impact of antibiotic susceptibility reporting on broad spectrum antibiotic use in serratia and morganella bacteremia
Published in Journal of Chemotherapy, 2022
Wendy Hui Wen Ng, Ka Lip Chew, Joy Hui Yan Yong, Janice Xuanhui Li
In a recent in-vitro study evaluating 237 isolates by Kohlmann et al [12], the mutation rates were considerably lower in Providencia spp., Serratia spp. (2 × 10−10), and especially Morganella morganii (5 × 10−11) isolates [12]. Conversely, Enterobacter spp., Citrobacter freundii complex and Hafnia alvei isolates were found to have a high mutation rates, with a mean mutation rate of 3 × 10−8. The treatment approach to ESCPM organisms may need to be reconsidered in light of these differences. A recent review highlighted that emergence of 3rd generation cephalosporin resistance among ESCPM organisms appear to be multifactorial and not only dependent on 3rd generation cephalosporin exposure [13]. Given the heterogeneity of these organisms with regards to induction and de-repression rates, they suggest that the possibility of using 3rd generation cephalosporins for the treatment of ESCPM organism should not be dismissed.
Mortality associated with third generation cephalosporin-resistance in Enterobacteriaceae infections: a multicenter cohort study in Southern China
Published in Expert Review of Anti-infective Therapy, 2021
Jiancong Wang, Mouqing Zhou, Therese Hesketh, Evangelos I. Kritsotakis
The following indicator organisms in the Enterobacteriaceae family were included for analysis: E. coli, Klebsiella pneumoniae, Klebsiella spp., Enterobacter spp., Citrobacter spp., and other Enterobacteriaceae species (i.e. Morganella, Proteus, Providencia, Serratia, and Salmonella species). Microbiological identification and susceptibility testing were performed using VITEK® 2 (BioMérieux, Marcy l’Etoile, France). The breakpoints for minimal inhibitory concentration (MIC) were based on the US National Clinical and Laboratory Standards Institute guidelines (modified version based on M100-28th edition in 2017) [20]. The indicator antimicrobial for third-generation cephalosporin resistance was ceftriaxone, with an MIC≤1 defining susceptibility and an MIC ≥2 defining resistance.