Michael Dan

Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens

This study evaluated whether trimethoprim-sulfamethoxazole (TMP-SMX) is effective for treatment of uncomplicated urinary tract infections (UTIs) due to TMP-SMX-resistant (TMP-SMX-R) pathogens. Healthy nonpregnant premenopausal women with symptomatic lower UTI were assessed for the presence of pyuria and bacteriuria; if either was present, a urine sample was cultured and TMP-SMX was prescribed. Clinical and microbiologic cure was assessed at days 5-9 and 28-42 after cessation of therapy. For 71%, of patients, cultures grew TMP-SMX-susceptible (TMP-SMX-S) microorganisms, and for 29%, cultures grew TMP-SMX-R organisms. Escherichia coli remained the predominant bacteria in both groups of cultures. At visit 2, microbiological cure had been achieved in 86% of the patients in the TMP-SMX-S group and 42% of those in the TMP-SMX-R group. Similar differences were found at visit 3 by clinical evaluation. Treatment with TMP-SMX of uncomplicated UTI caused by TMP-SMX-R microorganisms results in microbiologic and clinical failure. In high-resistance areas, TMP-SMX should not be the empiric drug of choice for uncomplicated UTI.

Cranberry Juice and Urinary Tract Infection

Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). Cranberries contain 2 compounds with antiadherence properties that prevent fimbriated Escherichia coli from adhering to uroepithelial cells in the urinary tract. Approximately 1 dozen clinical trials have been performed testing the effects of cranberries on the urinary tract. However, these trials suffer from a number of limitations. Most importantly, the trials have used a wide variety of cranberry products, such as cranberry juice concentrate, cranberry juice cocktail, and cranberry capsules, and they have used different dosing regimens. Further research is required to clarify unanswered questions regarding the role of cranberries in protecting against UTI in general and in women with anatomical abnormalities in particular.

Pyrazinamide-induced granulomatous hepatitis

Noncaseating granulomatous hepatitis may be caused by a variety of drugs, but we have not found, by computer search of the literature, a previous describe of granulomatous hepatitis associated with pyrazinamide. We describe a 52-year-old man with hectic fever, chills, extreme fatigue, liver damage, and hyperuricemia about 4 weeks after commencing pyrazinamide therapy. A liver biopsy specimen showed noncaseating epithelioid granulomas. The patient recovered soon after the interruption of tuberculostatic treatment.

Pregnancy-Associated Listeriosis: Clinical Characteristics and Geospatial Analysis of a 10-Year Period in Israel

BACKGROUND Listeria monocytogenes is a foodborne pathogen that causes life-threatening infections in elderly, immunocompromised, and pregnant women. In pregnancy it may cause fetal loss or a preterm delivery, and the neonate is prone to neonatal sepsis and death. METHODS We created a cohort of all L. monocytogenes cases during 10 years (1998-2007) in Israel, by a comprehensive review of cases in hospitals throughout the country and cases reported to the Ministry of Health. RESULTS One hundred sixty-six pregnancy-related listeriosis cases were identified, resulting in a yearly incidence of 5-25 cases per 100 000 births. Presentation associated with fetal demise was more common in the second trimester (55.3%), and preterm labor (52.3%) and abnormal fetal heart rate monitoring (22.2%) were more common in the third trimester (P = .001). Fetal viability was low in the second trimester (29.2%) and much higher (95.3%) in the third trimester. Each additional week of pregnancy increased the survival chance by 33% (odds ratio, 1.331 [95% confidence interval, 1.189-1.489]). A single case of maternal mortality was identified. Listeria monocytogenes serotype 4b was more common in pregnancy-related than in non-pregnancy-related cases (79.5% vs 61.3%, P = .011). Pulsed-field gel electrophoresis analysis suggested that 1 pulsotype is responsible for 35.7% of the pregnancy cases between 2001 and 2007. This clone is closely related to the Italian gastroenteritis-associated HPB2262 and the invasive US Scott A L. monocytogenes strains. CONCLUSIONS Our survey emphasizes the high rate of pregnancy-related listeriosis in Israel and shows that specific clones might account for this.

The effect of poly (ADP-ribose) polymerase inhibition on aminoglycoside-induced acute tubular necrosis in rats.

INTRODUCTION Aminoglycosides (AG) cause nephrotoxicity in 10 - 20% of patients. One of the mechanisms is by generating reactive oxygen species (ROS), leading to DNA destruction and activation of poly(ADPribose) polymerase (PARP) causing necrotic tubular cell death. PARP inhibition on gentamicin-induced nephrotoxicity was studied. METHODS 19 female Wistar-Kyoto rats divided into 3 groups: control (3 rats receiving no treatment); gentamicin-treated group (8 rats); and 8 rats treated with gentamicin combined with 3-aminobenzamide (3 AB). Kidney functions, protein, and gentamicin levels as well as urinary trypsin inhibitory activity (TIA) were measured. Tissue microscopic examination and immunohistochemical study for proliferative cell nuclear antigen (PCNA) were determined. The effect of PARP inhibitor on the bactericidal activity of gentamicin was also assessed. RESULTS The following results were statistically significant: urea (mg/dL) 39.9 ± 5.86, 88.3 ± 50.3, and 48.5 ± 12.7 (p = 0.048); serum creatinine (mg/dL): 0.6 ± 0.26, 1.05 ± 0.7, 0.6 ± 0.06 (p = 0.043); proteinuria (mg/24-hours): 7.27 ± 3.65, 41.2 ± 18.1, and 17.6 ± 13.9 (p = 0.050); the number of tubular macronuclei (per 10 mm2): 18.33 ± 16.07, 218 ± 101.8, 41.7 ± 36.2 (p = 0.012); the number of dilated tubes (per 10 mm2): 61.67 ± 12.58, 276.3 ± 112.7, 140.0 ± 90.9 (p = 0.04); and the number of PCNA positive nuclei (per 10 mm2): 223.3 ± 95.69, 3,585 ± 2,215.3, 626.7 ± 236.9 (p = 0.034) in the control, gentamicin, and gentamicin+3AB-treated groups, respectively. The following biochemical and histologic parameters were also examined, however, they showed no statistically significant difference: TIA (p = 0.055), mitoses (p = 0.14), mononuclear infiltrate (p = 0.188), and intratubular cast formation (p = 0.084). No effect on bactericidal activity was observed. CONCLUSION This study illustrates that PARP inhibitor significantly attenuates gentamicin-induced nephrotoxicity in rats with no effect on the bactericidal activity.

Increase in the isolation rate of enterococci from urine since the introduction of fluoroquinolones

Abstract Objectives: In recent years, a sharp increase has been noted in The E. Wolfson Hospital, Holon, Israel, in the isolation rate of enterococci from urine samples. The purpose of the study was to examine whether this phenomenon was associated with a change in antibiotic use in the institution, Methods: The isolation rate of enterococci from urine samples and the amount of fluoroquinolones and cephalosporins utilized in three periods during 1987, 1990, and 1993 were calculated. Results: Fluoroquinolones were introduced in The E. Wolfson Hospital in 1988. Between 1990 and 1993, both the use of fluoroquinolones and the isolation of enterococci increased by 50%. No change in the use of cephalosporins was observed during the same period. Conclusions: The effect of the extensive use of fluoroquinolones on colonization by, and superinfection with enterococci is explained by the broad antibacterial spectrum of these agents on one hand and their mediocre in vitro activity against enterococci on the other. This association is particularly worrisome since it may contribute indirectly to the spread of vancomycin-resistant enterococci.