Short CommunicationCarbapenem-resistant-only Pseudomonas aeruginosa infection in patients formerly infected by carbapenem-susceptible strains
Introduction
Pseudomonas aeruginosa is one of the major nosocomial pathogens. Infections by P. aeruginosa are often difficult to treat because of their limited susceptibility to commonly used antimicrobial agents [1]. There are a limited number of antimicrobial agents with reliable activity against P. aeruginosa, including antipseudomonal penicillins, cephalosporins, fluoroquinolones and carbapenems. Carbapenems are often the most consistently effective agents for the treatment of serious P. aeruginosa infections [2]. However, resistance to carbapenems has risen steadily among P. aeruginosa and is often associated with resistance to other antibiotics [3].
Carbapenem resistance in P. aeruginosa typically occurs through the loss of OprD [4], an outer membrane protein regulating the entry of carbapenems. Loss of OprD is the major determinant of non-metallo-β-lactamase-mediated resistance to carbapenems [5]. In addition to inactivation of OprD, overexpression of the intrinsic efflux system (MexAB–OprM) or production of carbapenem-hydrolysing β-lactamases (AmpC) may also be related to the occurrence of carbapenem resistance [6].
Carbapenem resistance often occurs following prolonged treatment of P. aeruginosa-infected patients, and cross-resistance to other β-lactams has been observed [3]. However, rapid onset of selective carbapenem resistance during treatment occurred in 15 patients in our hospital; in all cases the isolates were initially carbapenem-susceptible (CS). Susceptibilities to all other tested β-lactams remained identical in the carbapenem-resistant (CR) and CS pairs.
This study sought to investigate the mechanism accounting for the occurrence of selective carbapenem resistance in P. aeruginosa isolates, with a hypothesis that this resistance results from a loss of OprD expression. Clinical features and risk factors associated with the occurrence of CR-only P. aeruginosa (CROPA) in these cases were also analysed.
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Bacterial strains and microbiological investigation
From 2007 to 2011, clinical isolates of P. aeruginosa from the microbiology laboratory of Chang Gung Memorial Hospital (Taoyuan, Taiwan) isolated from the same patient during the same hospitalisation that were initially CS and then became CR were collected for investigation. All isolates were identified by standard methods [7] and antimicrobial susceptibilities were determined by the standard disc diffusion method and Etest [8]. Susceptibility and resistance were defined according to the
Results
P. aeruginosa that were initially CS and then became selectively CR during the same hospitalisation were isolated from various specimens of 15 hospitalised patients, including blood (6 cases), ascites (4), wound discharge (2), sputum (1), pleural effusion (1) and pericardial effusion (1). Table 1 shows a comparison of demographic and clinical features of the cases with persistent infection and re-infection. Of the 15 cases, the mean age was 51.3 ± 23.9 years. Re-infection cases tended to be older
Discussion
This study showed that CROPA may appear during or soon after carbapenem treatment of patients infected with CS-PA. Most of the cases represented persistent infection, as isogenic paired strains were demonstrated.
It was demonstrated that mutational inactivation of oprD, resulting in loss of the porin OprD and affecting carbapenem penetration across the outer membrane, was the main mechanism of carbapenem resistance [13]. Sequence analysis of the oprD gene showed various routes of inactivation,
Acknowledgment
The authors thank the members of the Molecular Infectious Disease Research Center (Chang Gung Memorial Hospital, Taoyuan, Taiwan) for their suggestions and assistance in this study.
Funding: This study was supported by grants from the National Science Council, Taiwan [NSC 101–2314–B–182A–046].
Competing interests: None declared.
Ethical approval: Not required.
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