Conversion to colistin susceptibility by tigecycline exposure in colistin-resistant Klebsiella pneumoniae and its implications to combination therapy.

OBJECTIVES: This study investigated the effect of tigecycline exposure on susceptibility of colistin-resistant Klebsiella pneumoniae isolates to colistin and explored the possibility of antibiotic combination at low concentrations to treat colistin-resistant K. pneumoniae isolates. METHODS: Twelve tigecycline-resistant (TIR) mutants were induced in vitro from wild-type, colistin-resistant, and tigecycline-susceptible K. pneumoniae isolates. Antibiotic susceptibility was determined using the broth microdilution method. The deduced amino acid alterations were identified for genes associated with colistin resistance, lipid A biosynthesis, and tigecycline resistance. Expression levels of genes were compared between wild-type stains and TIR mutants using quantitative real-time polymerase chain reaction (PCR). Lipid A modification was explored using MALDI-TOF mass spectrometry. Time-killing assay was performed to assess the efficiency of combination therapy using low concentrations of colistin and tigecycline. RESULTS: All TIR mutants except one were converted to be susceptible to colistin. These TIR mutants had mutations in the ramR gene and increased expression levels of ramA. Three genes associated with lipid A biosynthesis, lpxC, lpxL, and lpxO, were also overexpressed in TIR mutants, although no mutation was observed. Additional polysaccharides found in colistin-resistant, wild-type strains were modified in TIR mutants. Colistin-resistant K. pneumoniae strains were eliminated in vitro by combining tigecycline and colistin at 2 mg/L. In this study, we found that tigecycline exposure resulted in reduced resistance of colistin-resistant K. pneumoniae to colistin. Such an effect was mediated by regulation of lipid A modification involving ramA and lpx genes. CONCLUSION: Because of such reduced resistance, a combination of colistin and tigecycline in low concentrations could effectively eradicate colistin-resistant K. pneumoniae strains.

Case-control study of the risk factors for acquisition of Pseudomonas and Proteus species during tigecycline therapy.

Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp.

Clinical Features and Treatment Outcomes of Bloodstream Infections Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli Sequence Type 131.

Despite the remarkable emergence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli sequence type 131 (ST131), the clinical features and outcomes of infections caused by ST131 remain poorly described. From 2011 to 2012, we collected ESBL-producing E. coli isolates from patients with bloodstream infections in 13 hospitals in Korea and compared clinical characteristics and outcomes between ST131 and non-ST131 clones. Of the 110 ESBL-producing isolates, the most common ST was ST131 (30.9%). Multivariate analysis showed that recent operation was the only variable associated with the ST131 clone; other comorbid conditions and clinical features were similar between ST131 and non-ST131 clones. CTX-M-14 and CTX-M-15 were the predominant types of ESBLs, and CTX-M-15 was significantly associated with ST131. The rate of nonsusceptibility to ciprofloxacin was higher in ST131 than in non-ST131 clones (94.1% vs. 75.0%). No significant differences in 30-day mortality rates were found between ST131 and non-ST131 clones. Multivariate analysis revealed that older age (odds ratio [OR]=5.39, 95% confidence interval [CI] 1.22-23.89; p=0.027), nosocomial infection (OR=4.81, 95% CI 1.15-20.15; p=0.032), and higher Pitt bacteremia score (OR=7.26, 95% CI 1.41-37.42; p=0.018) were independent risk factors for 30-day mortality. The ESBL-producing E. coli ST131 clone has emerged and disseminated in Korea. Our findings reveal similarities in clinical and demographic characteristics between ST131 and non-ST131 clones. Although a more resistant profile has been detected in ST131, patients with the ST131 clone did not exhibit a higher mortality rate.