Impact of multidrug-resistant Pseudomonas aeruginosa bacteremia on patient outcomes.

Trends of rising rates of resistance in Pseudomonas aeruginosa make selection of appropriate empirical therapy increasingly difficult, but whether multidrug-resistant (MDR) P. aeruginosa is associated with worse clinical outcomes is not well established. The objective of this study was to determine the impact of MDR (resistance to three or more classes of antipseudomonal agents) P. aeruginosa bacteremia on patient outcomes. We performed a retrospective cohort study of adult patients with P. aeruginosa bacteremia from 2005 to 2008. Patients were identified by the microbiology laboratory database, and pertinent clinical data were collected. Logistic regression was used to explore independent risk factors for 30-day mortality. Classification and regression tree analysis was used to determine threshold breakpoints for continuous variables. Kaplan-Meier survival analysis was used to compare time to mortality, after normalization of the patients' underlying risks by propensity scoring. A total of 109 bacteremia episodes were identified; 25 episodes (22.9%) were caused by MDR P. aeruginosa. Patients with MDR P. aeruginosa bacteremia were more likely to receive inappropriate empirical therapy (44.0% and 6.0%, respectively; P < 0.001) and had longer prior hospital stays (32.6 +/- 37.3 and 14.4 +/- 43.6 days, respectively; P = 0.046). Multivariate regression revealed that 30-day mortality was associated with multidrug resistance (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.9 to 24.0), immunosuppression (OR, 5.0; 95% CI, 1.4 to 17.5), and an APACHE II score of > or = 22 (OR, 29.0; 95% CI, 5.0 to 168.2). Time to mortality was also shorter in the MDR cohort (P = 0.011). Multidrug resistance is a significant risk factor for 30-day mortality in patients with P. aeruginosa bacteremia; efforts to curb the spread of MDR P. aeruginosa could be beneficial.

Prevalence, resistance mechanisms, and susceptibility of multidrug-resistant bloodstream isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an important pathogen commonly implicated in nosocomial infections. The occurrence of multidrug-resistant (MDR) P. aeruginosa strains is increasing worldwide and limiting our therapeutic options. The MDR phenotype can be mediated by a variety of resistance mechanisms, and the corresponding relative biofitness is not well established. We examined the prevalence, resistance mechanisms, and susceptibility of MDR P. aeruginosa isolates (resistant to > or =3 classes of antipseudomonal agents [penicillins/cephalosporins, carbapenems, quinolones, and aminoglycosides]) obtained from a large, university-affiliated hospital. Among 235 nonrepeat bloodstream isolates screened between 2005 and 2007, 33 isolates (from 20 unique patients) were found to be MDR (crude prevalence rate, 14%). All isolates were resistant to carbapenems and quinolones, 91% were resistant to penicillins/cephalosporins, and 21% were resistant to the aminoglycosides. By using the first available isolate for each bacteremia episode (n = 18), 13 distinct clones were revealed by repetitive-element-based PCR. Western blotting revealed eight isolates (44%) to have MexB overexpression. Production of a carbapenemase (VIM-2) was found in one isolate, and mutations in gyrA (T83I) and parC (S87L) were commonly found. Growth rates of most MDR isolates were similar to that of the wild type, and two isolates (11%) were found to be hypermutable. All available isolates were susceptible to polymyxin B, and only one isolate was nonsusceptible to colistin (MIC, 3 mg/liter), but all isolates were nonsusceptible to doripenem (MIC, >2 mg/liter). Understanding and continuous monitoring of the prevalence and resistance mechanisms of MDR P. aeruginosa would enable us to formulate rational treatment strategies to combat nosocomial infections.

Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin-tazobactam: implications on the appropriateness of the resistance breakpoint.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pharmacist-driven antimicrobial optimization in the emergency department.

PURPOSE: A pharmacist-driven antimicrobial optimization service in the non-trauma emergency department (ED) of an 864-bed non-profit tertiary care teaching hospital was reviewed to assess its value. Local antimicrobial resistance patterns of urine, wound, stool, and blood cultures were also studied to determine whether or not empiric prescribing practices should be modified. METHODS: A retrospective electronic chart review was performed for ED patients with positive cultures during two different three-month periods. During Period 1, ED nursing management performed positive culture follow-up. During Period 2, ED clinical pharmacists performed this role. The primary objective was to determine the value of the pharmacist-driven antimicrobial optimization service as measured by the number of clinical interventions made when indicated. The secondary objective was to examine resistance patterns of urine and wound isolates in order to determine if empiric prescribing patterns in the ED should be modified. RESULTS: During Period 1, there were 499 patient visits with subsequent positive cultures. Of those, 76 patients (15%) were discharged home. Nursing management intervened on 21 of 42 (50%) positive cultures that required an intervention; in Period 2, there were 473 patient visits with subsequent positive cultures, and 64 (14%) were discharged home. Pharmacists intervened on 24 of 30 (80%) cultures where an intervention was indicated resulting in a 30% increase in interventions for inappropriate therapy (p = 0.01). A review of the secondary objective revealed a 38% fluoroquinolone resistance rate of E. coli, the most frequently isolated urinary organism. CONCLUSION: Pharmacist-driven antimicrobial stewardship program resulted in a 30% absolute increase in interventions for inappropriate therapy as compared to the nursing-driven model. This stewardship program has further demonstrated the value of ED pharmacists. Pharmacist interventions should help to ensure that infections are resolved through modification of antimicrobial therapies for patients with bug-drug mismatches. The fluoroquinolone resistance rate indicates a need to consider alternative therapies for uncomplicated urinary tract infections. Nitrofurantoin remains with good coverage against E. coli and Enterococcus species but should be used in uncomplicated patients with normal renal function.

Treatment of gram-positive infections: past, present, and future.

The need for strategic planning for antimicrobial use has reached a critical point. The rise in resistant nosocomial and community gram-positive bacteria mandates appropriate antibiotic selection and dosing. The development of new compounds is not the answer, because many are based off existing structures to which bacteria have already developed resistance. New antimicrobial agents are falling to the resistant mechanisms developed by the bacteria, after only limited clinical exposure. Judicious use of antimicrobial agents and applying pharmacokinetic principles when dosing can help slow the rate of resistance.