Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: To document the effects of appropriate and inappropriate empirical antibiotic therapy on mortality in a cohort of patients with bacteraemia due to methicillin-resistant Staphylococcus aureus (MRSA) and to summarize effects with previous studies. METHODS: In the retrospective cohort study, episodes of clinically significant MRSA bacteraemia during a 15 year period were included. Polymicrobial episodes were excluded unless MRSA was isolated in more than one bottle and co-pathogens were given appropriate empirical antibiotic treatment. Appropriate empirical treatment was defined as matching in vitro susceptibility and started within 48 h of blood-culture taking, except for single aminoglycosides or rifampicin. We assessed univariate and multivariate associations between appropriate empirical therapy and 30 day all-cause mortality. Multivariable analysis was conducted using backward stepwise logistic regression. We reviewed all studies assessing the effects of appropriate empirical antibiotic treatment on mortality for MRSA infections and compiled adjusted odds ratios (ORs) using a random effects meta-analysis. RESULTS: Five hundred and ten episodes of MRSA bacteraemia were included. There were no cases of community-acquired infection. The 30 day mortality was 43.9% (224/510) and was stable throughout the study period. Mortality was significantly higher among patients receiving inappropriate (168/342, 49.1%) compared with those receiving appropriate (56/168, 33.3%) empirical antibiotic treatment, P = 0.001. In the adjusted analysis the OR was 2.15 [95% confidence interval (CI) 1.34-3.46]. Pooling of six studies using adequate methodology for the adjusted analysis resulted in an OR of 1.98 (95% CI 1.62-2.44). CONCLUSIONS: Appropriate empirical antibiotic treatment has a significant survival benefit in MRSA bacteraemia. Treatment guidelines should consider this benefit.

Penicillin and ceftriaxone susceptibility of Streptococcus pneumoniae isolated from cerebrospinal fluid of children with meningitis hospitalized in a tertiary hospital in Israel.

BACKGROUND: Streptococcus pneumoniae is now the predominant pathogen causing meningitis. The resistance of S. pneumoniae to penicillin and third-generation cephalosporins has grown steadily. OBJECTIVES: To assess the antibiotic susceptibility of S. pneumoniae isolated from the cerebrospinal fluid of children with meningitis, and determine the antibiotic regimen appropriate for suspected bacterial meningitis in Israel. METHODS: The study group included 31 children with 35 episodes of meningitis hospitalized from 1998 to 2006. S. pneumoniae isolates from the cerebrospinal fluid were tested for susceptibility to penicillin and ceftriaxone. RESULTS: Of the 35 isolates, 17 (48.6%) showed resistance to penicillin (minimum inhibitory concentration > or = 0.12 microg/ml). Only 3 isolates (8.6%) showed intermediate resistance to ceftriaxone (> or = 0.5 and < (2 microg/ml), and none showed complete resistance (MIC > or = 2 microg/ml). The rates of antibiotic resistance were higher in children who were treated with antibiotics prior to admission (penicillin 88.9% vs. 34.6%, P = 0.007; ceftriaxone 22.2% vs. 3.8%, P = 0.156). CONCLUSIONS: The rate of penicillin resistance is high in children with S. pneumoniae meningitis in Israel, especially in those treated with oral antibiotics prior to admission. Resistance to ceftriaxone is infrequent though not negligible. On the basis of these findings, current recommendations to empirically treat all children with suspected bacterial meningitis with ceftriaxone in addition to vancomycin until the bacterial susceptibility results become available are justified also in Israel.

Antibiotic resistance of Helicobacter pylori in Israeli children.

OBJECTIVES: To determine the antibiotic susceptibility of Helicobacter pylori isolates from Israeli children; assess the role of previous antibiotic use in the development of antibiotic resistance and examine the possibility of simultaneous colonization of strains with different resistance patterns in the same patients. MATERIAL AND METHODS: A prospective case-series design was used. The study group included 174 patients aged 1-18 years referred to the Schneider Children's Medical Center of Israel for gastroscopy over a 2.5-year period. Antibiotic susceptibility to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin was determined by E-test on gastric biopsies (2 per patient). Clinical and demographic data were obtained by questionnaire. RESULTS: Cultures for H. pylori yielded 55 isolates from 53 children. In treatment-naïve children, the prevalence rate of primary resistance to clarithromycin was 25% and to metronidazole, 19%. Respective rates in children previously treated for H. pylori infection were 42% (p = 0.22) and 52% (p = 0.016). Simultaneous resistance to both drugs was found in 13% of isolates (n = 7), all from children with previous treatment failure. No resistance was found to amoxicillin, tetracycline or levofloxacin. Clarithromycin resistance was associated with macrolide use for any indication during the previous year (p = 0.033). In 2 patients (3.8%), a different H. pylori strain was cultured from each biopsy. CONCLUSIONS: H. pylori resistance to clarithromycin and metronidazole is high in Israeli children, particularly in those previously treated for H. pylori infection, in whom culture-based treatment should be considered. The simultaneous colonization of multiple strains in a minority of patients needs to be further characterized.

Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor.

Cranberry constituents are known to exert anti-adhesion activity on H. pylori in vitro. To determine their possible additive effect to triple therapy with omeprazole, amoxicillin and clarithromycin (OAC), a double-blind randomized clinical study was carried out. One-hundred-seventy-seven patients with H. pylori infection treated with OAC for 1 week were randomly allocated to receive 250 mL of either cranberry juice (cranberry-OAC, n = 89) or placebo beverage (placebo-OAC, n = 88) twice daily and only cranberry juice or placebo beverage for the next 2 weeks. Treatment outcome was determined with the(13)C urea breath test ((13)C-UBT). An additional control group consisted of patients referred to the same center during the same period who were treated with OAC alone for 1 week (non-placebo-OAC, n = 712). Overall, the rate of H. pylori eradication ((13)C-UBT < 3.5) was 82.5%, with no statistically significant difference among the three arms. Analysis by gender revealed that for female subjects, the eradication rate was higher in the cranberry-OAC arm (n = 42, 95.2%) than in the placebo-OAC arm (n = 53, 86.8%) and significantly higher than in the non-placebo-OAC group (n = 425, 80%; p = 0.03). For males, the rate was nonsignificantly lower in the cranberry-OAC arm (n = 35, 73.9%) than in the placebo-OAC arm (n = 45, 80.0%) and non-placebo-OAC group (n = 287, 85.0%). These results suggest that the addition of cranberry to triple therapy improves the rate of H. pylori eradication in females.

In vitro activity of levofloxacin against Helicobacter pylori isolates from patients after treatment failure.

We tested the in vitro activity of levofloxacin (LEV), amoxicillin (AMP), clarithromycin (CLA), metronidazole (MET), and tetracycline (TET) against 70 clinical isolates of Helicobacter pylori recovered from 70 dyspeptic patients. All patients had previously failed 2 treatment regimens: first-line triple therapy with omeprazole, AMP, and CLA, and second-line quadruple therapy with omeprazole, MET, TET, and bismuth. Resistance to CLA, MET, and LEV was found in 65.7%, 57.1%, and 18.6% of isolates, respectively. Resistance to both CLA and MET was found in 32.8%, and to CLA, MET, and LEV in 12.8%. Only 4 of the isolates were resistant to both CLA and LEV, and none was resistant to LEV alone or to MET and LEV. Physicians should consider triple therapy with omeprazole, LEV, and AMP in patients unsuccessfully treated with first- and second-line regimens.

Co-trimoxazole-sensitive, methicillin-resistant Staphylococcus aureus, Israel, 1988-1997.

Among bloodstream methicillin-resistant Staphylococcus aureus (MRSA) isolates from adult patients in a single hospital, susceptibility to co-trimoxazole increased progressively from 31% in 1988 to 92% in 1997 (p<0.0001). If also observed in other institutions, these findings should encourage the performance of a clinical trial of sufficient size to compare co-trimoxazole to vancomycin in treating MRSA infections.