Epidemiologic surveillance of multidrug-resistant bacteria in a teaching hospital: A 3-year experience.

BACKGROUND: The objective of this prospective study was to verify the effectiveness of a multidisciplinary surveillance program that was implemented in a teaching hospital in southern Brazil, to prevent and control the spread of multidrug-resistant organisms. METHODS: The program implemented involved establishment of prevention guidelines, hand-hygiene promotion, isolation of patients colonized or infected by such organisms, enforced contact precautions, and terminal cleaning and disinfection of isolation rooms. A microbiology service, previously provided by an external laboratory, was established in the hospital. Detection of bacteria-resistant genes and molecular typing were performed also. RESULTS: Statistically significant differences were observed between the pre- and post-intervention periods (P = .00198). Control measures were effective in blocking the dissemination of a previously endemic clone of Acinetobacter baumannii. Changes were observed in the dissemination pattern, from a monoclonal to a polyclonal mode. The incidence of vancomycin-resistant Enterococcus during the surveillance period was low. Only 2 isolates of BLAKPC-positive Klebsiella pneumoniae (distinct profiles), and 5 isolates of BLASPM-positive Pseudomonas aeruginosa (a single cluster), were detected. CONCLUSIONS: These results indicate that the surveillance program implemented was effective in preventing the spread of multidrug-resistant organisms in the hospital.

Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae.

KPC-producing Klebsiella pneumoniae causes serious infections associated with high death rates worldwide. Combination therapy consisting of fosfomycin and a carbapenem is better than monotherapy to combat multidrug-resistant microorganisms, but no dosages for the combination have been defined. The MICs of meropenem and fosfomycin were evaluated against 18 clinical isolates of KPC-2-producing K. pneumoniae The activities of combination antimicrobials were also determined by the checkerboard method. The MIC50 and MIC90 of each agent alone and in combination were challenged against short (1.5-h) or prolonged (3-h) infusion regimens of meropenem (1 g every 8 h [q8h], 1.5 g q6h, 2 g q8h) and fosfomycin (4 g q8h, 6 g q6h, 8 g q8h) by Monte Carlo simulation to evaluate the time above the MIC of the free drug concentration as a percentage of the dosing interval (fT>MIC). The monotherapy MIC50s and MIC90s were 32 and 256 mg/liter for meropenem and 64 and 512 mg/liter for fosfomycin, respectively. Antimicrobial combination increased bacterial susceptibility to 1/4 the MIC50s and to 1/8 to 1/16 the MIC90s of monotherapy. The antimicrobial combination demonstrated a synergistic effect for at least two-thirds of the isolates. In combination therapy, fosfomycin regimens of 6 g q6h and 8 g q8h as a 3-h infusion against the MIC50 and MIC90 had better chances of achieving ≥90% probability of target attainment (PTA) of 70% fT>MIC. Meropenem regimens of 1.5 g q6h and 2 g q8h in prolonged infusion can achieve close to 90% PTA of 40% fT>MIC for MIC50 but not MIC90 The significant reduction in the MIC values and the achievement of appropriate PTA demonstrated that regimens containing fosfomycin with meropenem can be effective against KPC-2-producing K. pneumoniae.