PATIENTS AND METHODS: With concern over its rising microbial resistance, we explored the association of empiric antibiotics choices with the hospital outcomes of patients treated for microbial proven K. pneumoniae pneumonia in an urban-based teaching hospital.
RESULTS: In 313 eligible cases reviewed retrospectively, hospital mortality and requirement for ventilation were 14.3% and 10.8% respectively. Empiric regimes that had in vitro resistance to at least one empiric antibiotic (n = 90) were associated with higher hospital mortality (23.3% vs. 10.8%, P = 0.004) with risk increased by about two-fold [Odds ratio (OR), 2.5; 95% confidence interval (CI), 1.3 to 4.8]. Regimes (n = 84) other than the commonly recommended "standard" regimes (a beta-lactam stable antibiotic with or without a acrolide) were associated with higher ventilation rates (16.7% vs. 8.8%, P = 0.047) with similar increased risk [OR, 2.0; 95% CI, 1.0 to 4.3].
CONCLUSIONS: Our findings reiterate the clinical relevance of in vitro microbial resistance in adult K. pneumoniae pneumonia and support empiric regimes that contain beta-lactam stable antibiotics.
MATERIALS AND METHODS: Febrile neutropenic patients treated between January 1996 and December 1997 at the pediatric oncology unit of University Hospital, Kuala Lumpur, were prospectively studied. Empirical antibiotic therapy consisted of ceftazidime and amikacin. Those who developed K. pneumoniae bacteremia were identified, and clinical features analyzed. Ceftazidime-resistance was documented via disk-diffusion testing. Production of extended-spectrum beta-lactamase (ESBL) was inferred on the basis of synergy between ceftazidime and amoxicillin-clavulanic acid. The different features between the two groups and variables associated with the development of CRKP bacteremia were analyzed using chi-square and t-tests and calculation of odds ratios. A multivariate analysis was used to identify independent factors for CRKP development.
RESULTS: Ceftazidime-resistance was seen in 51.6% of all K. pneumoniae isolates, and all these isolates were inferred to be ESBL producers. All isolates were sensitive to imipenem. Susceptibility to gentamicin was 90.5%. The mean continuous hospital stay prior to the detection of bacteremia was 13.7 days overall, but significantly longer in the CRKP group (21.9 d) compared to the CSKP group (4.3 d) (P = 0.003). Children with CRKP were more likely to have received antibiotics in the 2 weeks prior to detection of bacteremia (87.5% of cases) than the CSKP group (20.0% of cases) (P = 0.0008). Sepsis-related mortality was higher in those with CRKP (50.0%) than in the CSKP group (13.3%) (P = 0.02). Patients who did not receive CRKP-directed antibiotics within 48 hours of admission were more likely to have a fatal outcome than those who did (P = 0.009). Logistic regression analysis identified use of third-generation cephalosporins 2 weeks prior to presentation and a hospital stay of 2 weeks or more as independent risk factors for development of CRKP.
CONCLUSIONS: More than half of total K. pneumoniae isolated from blood cultures in the unit were ceftazidime-resistant. Children with febrile neutropenia with prolonged hospital stay and recent prior antibiotic exposure are at high risk of developing CRKP bacteremia. Mortality was significantly higher in this group. Early commencement of appropriate antibiotics (e.g., imipenem with or without gentamicin), according to susceptibility study results, may be beneficial in such circumstances.