tigecycline and Cross-Infection

Tigecycline is a new-generation of tetracycline (glycylcyclines) and is active in vitro against bacteria that possess any of the classical genes that confer tetracycline resistance through ribosomal protection or efflux pumps. Herein, tigecycline disposition in patients with community- or hospital-acquired pneumonia was described using a population pharmacokinetic model. Additionally, the influence of covariates, such as body surface area, severity of illness, and clinical laboratory measures, on tigecycline disposition was evaluated. An intravenous loading dose of 100 mg was followed by 50 mg of tigecycline every 12 h. The final population pharmacokinetic model was a two-compartment model with linear elimination and with a relationship between tigecycline clearance and body surface area and creatinine clearance. The model was parameterized using total clearance (CL), the volume of the central compartment, distributional clearance from the central to the peripheral compartment, and volumes of distribution at steady state. Relationships between body surface area and creatinine clearance were identified as significant predictors of interindividual variability on CL. This model will serve as the basis for estimating tigecycline exposure for pharmacokinetic-pharmacodynamic analyses for efficacy and safety among patients with community- or hospital-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia; Tigecycline; Young Adult

Seven carbapenem-resistant NDM-1-positive Klebsiella pneumoniae isolates were recovered from patients hospitalized between 2007 and 2009 in different wards at a referral and tertiary care center in Nairobi. Most of the isolates were obtained from urine. All isolates carried the bla(NDM-1) carbapenemase gene previously reported from India, Pakistan, and the United Kingdom. These isolates were clonally related and expressed many other resistance determinants, including β-lactamases CTX-M-15, OXA-1, OXA-9, CMY-6, and aminoglycoside resistance methylase RmtC. This work corresponds to the first report of NDM-1 producers in Africa.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Kenya; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction

The resistance mechanism of 49 Enterobacteriaceae isolates with decreased susceptibility to carbapenems collected from 2004 to 2008 at 16 teaching hospitals in China was investigated. Moderate- to high-level carbapenem resistance in most isolates was more closely associated with loss or decreased expression of both major porins combined with production of AmpC or extended-spectrum beta-lactamase enzymes, while KPC-2, IMP-4, and IMP-8 carbapenemase production may lead to a low to moderate level of carbapenem resistance in Enterobacteriaceae in China.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Genotype; Integrons; Microbial Sensitivity Tests; Phenotype; Population Surveillance; Porins; Reverse Transcriptase Polymerase Chain Reaction