Current Clinical Laboratory Standards Institute Research Articles

Impact of inappropriate antifungal therapy according to current susceptibility breakpoints on Candida bloodstream infection mortality, a retrospective analysis

BackgroundThe mortality of Candida Bloodstream Infection (CBSI) remains high. Antifungal susceptibility breakpoints were recently updated for Candida species, the impact remains unknown. In this study we evaluated the impact of inappropriate antifungal treatment according to recent breakpoints on 30-day mortality of CBSI.MethodsFrom June 2008 to July 2014, data on CBSI episodes from two tertiary-care centers, treated > 72 h were analyzed. Antifungal therapy and 30-day mortality were registered. Inappropriate antifungal treatment according to current Clinical & Laboratory Standards Institute (CLSI) breakpoints was adjusted with 30-day mortality-related co-variates.ResultsOne hundred forty-nine episodes of CBSI were analyzed. The most frequent species were: C. albicans (40%), C. tropicalis (23%) and C. glabrata complex (20%). According to the 2012 CLSI, 10.7% received inappropriate treatment. The 30-day mortality was 38%; severe sepsis [Odds ratio (OR) 3.4; 95% CI 1.3–8.4], cirrhosis (OR 36; 95% CI 12.2–605), early central venous catheter removal (OR 0.23; 95% CI 0.08–0.66) and previous antifungal therapy (OR 0.15; 95%CI 0.03–0.62), were associated with 30-day mortality by multivariate analysis. Inappropriate antifungal treatment was not (OR 0.19; 95% CI 0.03–1.2).ConclusionsAppropriate antifungal therapy according to CLSI 2012 did not have an impact on mortality. Mortality of CBSI remains high due to disease severity and comorbidities; early antifungal therapy and catheter removal may reduce it.

Antibiotic susceptibility pattern of Salmonella enterica serovar typhi and Salmonella enterica serovar paratyphi A with special reference to quinolone resistance

Background and Objectives: Typhoid fever is endemic in India. Extensive use of first-line antibiotics has led to the emergence of multi-drug resistant (MDR) Salmonella typhi. Ciprofloxacin has become empirical therapy of choice against MDR salmonellae. Recent year's emergence of low-level ciprofloxacin resistance in salmonellae resulted in delayed response and serious complications. Nalidixic acid (NA) screen test is used as surrogate marker for detection low-level ciprofloxacin resistance. In this study, we evaluated prevalence of MDR and low-level ciprofloxacin resistant S. typhi and Salmonella paratyphi A. Materials and Methods: A total of 50 blood culture isolates of S. typhi and S. paratyphi A were tested for antibiotic susceptibility according to Clinical Laboratory Standards Institute (CLSI) method. Minimal inhibitory concentration (MIC) to ciprofloxacin was carried out by E-test and agar dilution method. Results: Among the 50 salmonella isolates, 80% were S. typhi and 20% were S. paratyphi A. MDR was found in 2% S. typhi. NA resistant salmonellae showed ciprofloxacin MIC ranging from 0.25 to 0.75 μg/ml. One isolate of S. typhi showed ciprofloxacin MIC of 32 μg/ml and was also resistant to ceftriaxone. NA screen test for low-level ciprofloxacin resistance was 100% sensitive and 97.9% specific. Interpretation and Conclusion: NA resistant isolates should be tested for ciprofloxacin MIC to decide therapeutic options. The current CLSI breakpoints may have to be re-evaluated for salmonellae.

Investigation of the clinical breakpoints of piperacillin–tazobactam against infections caused by Pseudomonas aeruginosa

The pharmacokinetics-pharmacodynamics (PK-PD) breakpoint of piperacillin/tazobactam (PIPC/TAZ) for hospital-acquired pneumonia (HAP) and Pseudomonas aeruginosa-induced bacteremia is controversial, since the susceptibility of P. aeruginosa to PIPC/TAZ is known to be lower than that set by the Clinical Laboratory Standards Institute (CLSI), ≤64 mg/L. The association between MIC levels and bacterial eradication after various PIPC/TAZ treatments was investigated. In all, 61 and 17 Japanese patients from the microbiology laboratory database with HAP and P. aeruginosa-induced bacteremia, respectively, who were treated with PIPC/TAZ (4.5 g, b.i.d., t.i.d., or q.i.d.) between 2008 and 2009 were retrospectively analyzed. Pertinent clinical data were retrieved from medical records. The MIC level was determined using the microdilution method. Appropriate empirical therapy with PIPC/TAZ was selected for all patients within 24 h of positive culture results. The microbiological effect after treatment was used to determine the efficacy of each PIPC/TAZ administration method. In PIPC/TAZ-treated HAP patients (4.5 g, t.i.d.), the microbiological efficacy was 93.3% (28/30) when the MIC was ≤16 mg/L, while it was 50.0 (5/9) and 0% (0/3) with MICs of 32 (p < 0.05) and 64 mg/L, respectively. In PIPC/TAZ-treated bacteremia patients (4.5 g, t.i.d. or q.i.d.), the microbiological efficacy was 100% (11/11) when the MIC was <16 mg/L, while it was 33.3 (1/3) and 0% (0/3) with MICs of 32 (p < 0.05) and ≥64 mg/L, respectively. The present CLSI susceptibility breakpoints do not necessarily predict clinical outcomes. The appropriateness evaluation of the current CLSI resistance breakpoint of PIPC/TAZ and the PK-PD breakpoint determination warrant further studies.

Outcomes of Bacteremia due to Pseudomonas aeruginosa with Reduced Susceptibility to Piperacillin-Tazobactam: Implications on the Appropriateness of the Resistance Breakpoint

Bacteremia due to Pseudomonas aeruginosa is associated with grave clinical outcomes. Recent studies have emphasized the importance of appropriate empirical therapy, but controversy arises when piperacillin-tazobactam is used against isolates with reduced susceptibility. We performed a retrospective cohort study of pseudomonal bacteremia from 2002 to 2006. Patients were identified by the microbiology laboratory database, and pertinent clinical data (demographic characteristics, baseline Acute Physiology and Chronic Health Evaluation [APACHE] II scores, source of bacteremia, and therapy) were retrieved from the electronic medical records. All patients received appropriate empirical therapy within 24 h of positive culture results. Patients receiving piperacillin-tazobactam were compared with those receiving other agents (control subjects). The primary outcome was 30-day mortality from the first day of bacteremia. A total of 34 bacteremia episodes were identified involving isolates with reduced susceptibility to piperacillin-tazobactam (minimum inhibitory concentration, 32 or 64 mg/L, reported as susceptible); piperacillin-tazobactam was empirically given in 7 episodes. There was no significant difference in baseline characteristics between the 2 groups. Thirty-day mortality was found to be 85.7% in the piperacillin-tazobactam group and 22.2% in the control group (P = .004). Time to hospital mortality was also found to be shorter in the piperacillin-tazobactam group (P < .001). In the multivariate analysis, 30-day mortality was found to be associated with empirical piperacillin-tazobactam therapy (odds ratio, 220.5; 95% confidence interval, 3.8-12707.4; P = .009), after adjustment for differences in age and APACHE II score. In P. aeruginosa bacteremia due to isolates with reduced piperacillin-tazobactam susceptibility, empirical piperacillin-tazobactam therapy was associated with increased mortality. Additional studies are warranted to examine the appropriateness of the current Clinical Laboratory Standards Institute resistance breakpoint of piperacillin-tazobactam.

Multidrug-ResistantAcinetobacter baumanniiOsteomyelitis from Iraq

Multidrug-Resistant<i>Acinetobacter baumannii</i>Osteomyelitis from Iraq

Detection of plasmid-mediated AmpC in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis

Aims:This study investigated the prevalence of plasmid-mediated AmpC production in selected clinical isolates of Escherichia coli, Klebsiella species and Proteus mirabilis, and compared the results of boronic acid disc screening...

Reevaluation of current susceptibility breakpoints for Gram-negative rods based on pharmacodynamic assessment

Although pharmacodynamic (PD) modeling is now being considered for decision support for susceptibility breakpoint determination against Gram-negative bacteria, these PD-derived breakpoints should be verified using a clinically applicable population of organisms. In this analysis, a 5000-patient Monte Carlo simulation was used to determine PD breakpoints, the highest 2-fold MIC in which the probability of bactericidal target attainment (PTA) remained ≥90%. Percent susceptibilities for 639 Pseudomonas aeruginosa, 103 Acinetobacter baumannii, 705 Escherichia coli, and 418 Klebsiella spp. collected during the 2004 Meropenem Yearly Susceptibility Test Information Collection surveillance study were then defined according to the PD-derived breakpoint (% S PD) and compared with the current Clinical Laboratory Standards Institute (CLSI)-defined breakpoints (% S CLSI). % S PD and % S CLSI were compared with the bactericidal PTA for each pathogen population to determine the degree of agreement. Resulting PD breakpoints were drug and dose dependent; moreover, values were commonly 2 to 4 MIC dilutions lower than CLSI breakpoints. Overall, % S PD more closely agreed with the PTA for the tested β-lactam and fluoroquinolone dosing regimens. In contrast, % S CLSI overestimated PTA for many dosing regimens, especially against Pseudomonas: piperacillin/tazobactam 4.5 g qid (+9.7%), ciprofloxacin 0.4 g bid (+13.7%) and 0.4 g tid (+9.3%), and levofloxacin 0.5 g every 24 h (+22.4%) and 0.75 g every 24 h (+9.9%). Differences were most pronounced against the nonfermenting Gram-negative bacteria and were not observed among the Enterobacteriaceae. As a result, a new method of breakpoint classification is proposed, which is dosing regimen and pathogen specific, and is designed to denote isolates as susceptible only if target bactericidal exposures are achievable with the dosing regimen selected.