Tigecycline for Treatment of Pneumonia and Empyema Caused by Carbapenemase‐Producing Klebsiella pneumoniae

Abstract

Strains of Klebsiella pneumoniae that produce one of three possible carbapenemases--KPC--have recently been identified with increasing frequency among isolates recovered from patients residing along the East Coast of the United States, particularly within the New York City metropolitan region. These strains have exhibited resistance to multiple antibiotic classes, including carbapenem agents. We report a case of nosocomial pneumonia and empyema caused by a KPC-producing isolate of K. pneumoniae at a large midwestern U.S. tertiary care facility in which the patient was treated with tigecycline. Although the pneumonia was treated successfully, the empyema recurred in association with a treatment-emergent tigecycline minimum inhibitory concentration (MIC) increase from 0.75 to 2 microg/ml. Clinicians should be aware of the potential occurrence of this treatment-emergent MIC increase, especially in the setting of sustained tigecycline therapy. In addition, the emergence of carbapenem-resistant Enterobacteriaceae reinforces the importance of antibiotic stewardship and strict infection control practices.

Superinfection during treatment of nosocomial infections with tigecycline

“…Tigecycline administered in healthy subjects significantly reduced the numbers of enterococci, E. coli, lactobacilli, and bifidobacteria, and increased Candida albicans, K. pneumoniae, and E. cloacae, and some patients (7/12) presented colonization by resistant strains to tigecycline on day 8 [12]. Also, an increase in tigecycline MIC during tigecycline treatment against A. baumannii and K. pneumoniae infections, and bloodstream infections and other infections caused by tigecycline-non-susceptible A. baumannii have been observed [13][14][15].…”

What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline

“…Furthermore, colistin-resistant variants of the international KPC + ST258 K. pneumoniae strain are circulating in Greece and Hungary [13,14], with a few cases also seen in the UK. In the case of tigecycline, there are positive case reports of its use in infections due to K. pneumoniae with VIM and KPC carbapenemases in Greece [15], but also of resistance emerging during therapy, albeit in an off-label setting (nosocomial pneumonia) [16]. Moreover, it is licensed for use only in intra-abdominal and complicated skin and skin-structure infections, and proved inferior to imipenem/cilastatin in ventilator-associated pneumonia, providing a caution against off-label use in this infection [17].…”

“…Chloramphenicol, ciprofloxacin and nitrofurantoin inhibited <25% of the isolates at the breakpoint, whereas colistin was active against 75/81 isolates (92.6%), the exceptions being four Klebsiella pneumoniae and Enterobacter cloacae isolates along with members of inherently resistant genera. Fosfomycin was active against 49/81 isolates (60.5%), including 7/7 Escherichia coli, 16 M a n u s c r i p t…”

In Vitro Pharmacodynamics of Simulated Pulmonary Exposures of Tigecycline Alone and in Combination against Klebsiella pneumoniae Isolates Producing a KPC Carbapenemase

“…Although in vitro data suggest that tigecycline will be a useful antibiotic in managing infections caused by KPC-producing organisms, clinical and experimental data to support its use are limited. To date, one case report has described the use of tigecycline monotherapy for pneumonia and empyema caused by KPC-producing K. pneumoniae (15). While the patient's pneumonia was treated successfully, the empyema recurred and the tigecycline MIC increased from 0.5 to 2 g/ml while the patient underwent prolonged tigecycline therapy.…”