Influence of extended-spectrum beta-lactams on gram-negative bacterial resistance.

PURPOSE: The influence of extended- spectrum beta-lactams on gram-negative bacterial resistance was studied. METHODS: Hospital pharmacists were asked to provide data on antimicrobial use and bacterial susceptibilities. Defined daily doses per 1000 patient-days of cefepime, ceftazidime, ceftriaxone, and piperacillin-tazobactam were assessed for significant associations with gram-negative susceptibility. To account for midyear changes in usage patterns and the lag between changes in usage and resistance, susceptibility over two-year periods was evaluated. RESULTS: Susceptibility data of more than 300,000 gram-negative isolates, representing 10 species of interest, were provided by 82 U.S. hospitals. Two-year periods (n = 45) were evaluable for 25 hospitals, containing 159 hospital-years of data and 204,513 clinical isolates. Use of cefepime increased, while use of ceftazidime, ceftriaxone, and piperacillin-tazobactam decreased. Excluding Pseudomonas aeruginosa, bacteria were most susceptible to cefepime, followed by piperacillin-tazobactam, ceftriaxone, and ceftazidime. Significantly decreased susceptibilities of gram-negative bacteria to the antibiotics themselves were observed with ceftazidime (Enterobacter aerogenes) and ceftriaxone (Escherichia coli). Extended-spectrum beta-lactams associated with significantly decreased susceptibilities of gram-negative bacteria to other beta-lactams included cefepime (E. aerogenes and E. coli susceptibility to ceftazidime), ceftazidime (Enterobacter cloacae susceptibility to cefepime), ceftriaxone (E. cloacae susceptibility to cefepime), piperacillin-tazobactam (E. cloacae, Klebsiella pneumoniae, and P. aeruginosa susceptibility to cefepime). There were insufficient susceptibility data to allow for impact analysis for piperacillin-tazobactam. CONCLUSION: Use of cefepime, ceftazidime, ceftriaxone, and piperacillin-tazobactam was associated with variably changing susceptibilities of several key gram-negative bacteria, either to themselves or to each other. Despite the increased use of cefepime, gram-negative bacterial susceptibility to cefepime remained high.

Observations on vancomycin use in U.S. hospitals.

PURPOSE: Current knowledge and policies regarding vancomycin use and the clinical performance of vancomycin in U.S. hospitals were assessed. METHODS: A questionnaire was sent to interested hospital pharmacists. An observational study of hospitalized adults who received at least 72 hours of i.v. vancomycin for a culture-confirmed gram-positive infection followed. Hospital antibiograms were obtained for gram-positive susceptibility data. RESULTS: A total of 59 respondents completed the survey. Survey results revealed that vancomycin is rarely restricted. Investigators from 24 hospitals, 16 (67%) of which were teaching facilities, collected retrospective data from the records of 200 patients. Infection sites included blood, lower respiratory tract, and skin and soft tissue. Staphylococcus aureus was isolated from 52% of positive cultures; 75% of these were methicillin-resistant S. aureus (MRSA). Serum vancomycin concentrations were monitored in 95% of patients; results from 22 hospitals were evaluable. Trough serum vancomycin concentrations were higher in teaching versus nonteaching hospitals (p < 0.001). Peak serum vancomycin concentrations were also higher in teaching versus nonteaching hospitals (p < 0.05). Clinical responses from 22 hospitals were evaluable; the mean success rate of 82% did not significantly differ between teaching and nonteaching hospitals. Vancomycin- associated adverse events occurred in 13 patients (6.5%) and were reported more frequently for patients in teaching versus nonteaching hospitals (p = 0.02). CONCLUSION: Observational data suggest that vancomycin remains an effective antibiotic with infrequent discontinuations due to adverse events, and trough serum vancomycin concentrations are monitored routinely. Antibiogram data revealed that the prevalence of MRSA continues to increase.

Characterization of the onset and consequences of pneumonia due to fluoroquinolone-susceptible or -resistant Pseudomonas aeruginosa.

OBJECTIVES: This study was conducted to identify and compare the microbiological and clinical outcomes among hospitalized adults with pneumonia caused by fluoroquinolone-susceptible or -resistant strains of Pseudomonas aeruginosa. Antibiotic regimens used prior to, as well as those used to treat, the infections were characterized. PATIENTS AND METHODS: This non-randomized multicentre study included 100 consecutively identified patients with pneumonia caused by fluoroquinolone-susceptible (n = 50) or fluoroquinolone-resistant (n = 50) strains of P. aeruginosa. Medical records were examined for demographic, clinical and treatment variables including antibiotics received in the 30 days before the index respiratory or blood culture; AUICs were calculated for each patient using reported or derived MICs. Multivariate logistic and linear regressions were used to identify factors associated with successful clinical and microbiological outcomes. RESULTS: The study population was primarily elderly, frequently in a critical care unit, with low serum albumin and with a high probability of failure and mortality. Patients with pneumonia caused by fluoroquinolone-resistant P. aeruginosa were more likely to have received antibiotics within 7 days before the infection (P = 0.027); the antibiotic regimen was more likely to be of a weak potency (mean AUIC of 58 versus 169, P = 0.001) and to include levofloxacin (P < 0.0001) than what was administered to patients who became infected with a fluoroquinolone-susceptible strain. Regardless of susceptibility, a mean of between 2 and 3 weeks of directed antibiotic therapy was administered to each patient. CONCLUSIONS: Pneumonia caused by fluoroquinolone-resistant P. aeruginosa is frequently associated with prior exposure to levofloxacin. Treatment of P. aeruginosa pneumonia is difficult and usually consists of combination regimens with multiple modifications.

Economic consequences of antimicrobial resistance.

BACKGROUND: In the past two decades, a dramatic increase in the frequency and prevalence of antimicrobial-resistant pathogens has challenged clinicians and researchers. MATERIALS AND METHODS: A review of the literature was conducted. Available data identifying the costs and consequences of resistance are summarized while the issues and limitations of research assessing the economics of resistance are acknowledged. RESULTS: Microbial resistance is a complex, multifactorial phenomenon, but the single most powerful influence is antimicrobial use. Treatment guidelines, clinical pathways, and other directives exert widespread influences on individual selection of antimicrobial agents. However, use of an empiric regimen that does not provide effective coverage, or a targeted regimen that is dosed too low to provide optimal therapy, will delay eradication of the pathogen, increase the potential for resistance to emerge, extend and increase morbidity, and expose the patient to an increased risk of mortality. Coincident with these untoward clinical events are economic consequences secondary to increased duration of treatment, and for some, an extended duration of hospitalization. CONCLUSION: Resistant gram-negative and gram-positive bacteria have been associated with increased direct medical costs ranging from several thousand dollars to tens of thousands of dollars per patient.