Fosfomycin trometamol in the prophylaxis of post-kidney transplant urinary tract infection: A controlled, randomized clinical trial.

BACKGROUND: The aim of this controlled clinical trial was to evaluate the efficacy and safety of fosfomycin trometamol (FOS) in urinary tract infection (UTI) prophylaxis during the first 6 months after renal transplant (RT). METHODS: The intervention group received 3 g of FOS PO every 10 days and trimethoprim-sulfamethoxazole (TMP-SMX, 160/800 mg) three times per week (Group 1), whereas the control group received TMP-SMX (160/800 mg) daily (Group 2). The outcomes were the time until the first UTI (symptomatic infection or asymptomatic bacteriuria (>105  CFU/mL)) and the incidence of UTI during the first 6 months post RT. Intermediate analysis was conducted after one-half of the estimated sample size of patients was enrolled. RESULTS: The recruitment of patients was stopped after the intermediate analysis due showed no emerging trends or reasonable chance of demonstrating benefit. Sixty-seven patients were included (32 in Group 1 and 35 in Group 2). The UTI incidence (40.6% vs 42.8%, P = 0.85) and time until the first episode were similar between the groups (log rank, P = 0.862). UTI due to Klebsiella spp. was observed in both groups at equal rates (25% vs 20%, P = 0.62), episodes due to Escherichia coli were less frequent in Group 1 (12.5% vs 34.2%, P = 0.04), and Enterococcus faecalis infection only occurred in Group 2 (n = 4). Resistance to FOS was observed for Klebsiella spp.; in contrast, E. coli and E. faecalis were susceptible. CONCLUSIONS: The addition of FOS to TMP-SMX was not beneficial for the prevention of UTI after RT in our setting. (ClinicalTrials.gov, NCT01820897).

Impact of ertapenem on antimicrobial resistance in a sentinel group of Gram-negative bacilli: a 6 year antimicrobial resistance surveillance study.

OBJECTIVES: To determine the association between ertapenem and resistance of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii-calcoaceticus complex to different antimicrobials while adjusting for relevant hospital factors. METHODS: This was a retrospective time-series study conducted at a tertiary care centre from September 2002 to August 2008. The specific impact of ertapenem on the resistance of these Gram-negative bacilli (GNB) was assessed by multiple linear regression analysis, adjusting for the average length of stay, rate of hospital-acquired infections and use of 10 other antimicrobials, including type 2 carbapenems. RESULTS: Unadjusted analyses revealed significant increases over the duration of the study in the number of GNB resistant to meropenem/imipenem among 1000 isolates each of E. coli (0.46 ±â€Š0.22, P < 0.05), P. aeruginosa (6.26 ±â€Š2.26, P < 0.05), K. pneumoniae (8.06 ±â€Š1.50, P < 0.0005) and A. baumannii-calcoaceticus complex (25.39 ±â€Š6.81, P < 0.0005). Increased resistance to cefepime (and other extended-spectrum cephalosporins) was observed in E. coli (9.55 ±â€Š1.45, P < 0.0005) and K. pneumoniae (15.21 ±â€Š2.42, P < 0.0005). A. baumannii-calcoaceticus complex showed increased resistance to all antimicrobials except amikacin. After controlling for confounders, ertapenem was not significantly associated (P > 0.05) with changes in resistance for any pathogen/antimicrobial combination. CONCLUSIONS: After controlling for confounders, ertapenem was not associated with changes in resistance in a group of sentinel GNB, although significant variations in resistance to different antimicrobials were observed in the unadjusted analyses. These results emphasize the importance of implementation of local resistance surveillance platforms and stewardship programmes to combat the global emergence and spread of antimicrobial resistance.

Epidemiology of adverse cutaneous drug reactions. A prospective study in hospitalized patients.

BACKGROUND: Drug reactions are commonly present in the skin; however, their frequency in our setting is unknown. METHODS: A 10-month prospective cohort study including all hospitalized patients was designed. Those with adverse cutaneous drug reactions (ACDR) were clinically identified. RESULTS: Thirty five drug reactions (prevalence of 0.7%) were seen among 4785 (2713 females, 2072 males) discharged patients. According to Begaud's imputability criteria, the reactions were most likely attributed to a drug in 4.87%, likely in 41.46% and possible in 53.65%. The most commonly seen dermatoses were morbilliform rash 51.2%, urticaria 12.2% and erythema multiforme 4.9%. Drugs most frequently associated with ACDR were amoxicillin clavulanate (8), amphotericin B (2) and metamizole (4). Expressed as risk by 1000 day-doses (Dd: the risk a patient has of developing an ACDR after receiving 1 day of treatment with the drug): amoxicillin clavulanate Dd 7.7, amphotericin B Dd 4.8 and metamizole Dd 3.7. Immunosuppressed patients were most frequently affected. Notably, patients with systemic lupus erythematosus (SLE) had a 4.68 higher risk (CI 95% 1.794-12.186 p <0.001) of developing an ACDR. AIDS patients showed a risk of 8.68 (CI 95% 2.18-33.19 p <0.001). Non-Hodgkin's lymphoma patients also had an increased risk of developing an ACDR. Six of the 35 identified cases were patients who had been hospitalized due to a severe drug reaction (1.3/1000 patients); one died from complications directly related to the ACDR, representing a 16.6% mortality rate among those admitted for an ACDR and 0.02% among the global mortality. CONCLUSIONS: We have a low prevalence of drug reactions compared to data reported in the literature. Pharmacovigilance with special attention to immunosuppressed SLE or AIDS patients is stressed.