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Indian Journal of Pharmacology, Vol. 38, No. 4, July-August, 2006, pp. 287-288 Research Letter Emerging resistance to carbapenems in hospital acquired Pseudomonas infection: A cause for concern Shashikala, Kanungo R, Srinivasan S, Devi Sheela Department of Clinical Microbiology, Pondicherry Institute of Medical Sciences, Pondicherry-605 006 Code Number: ph06076 An increasing number of organisms, in healthcare associated infections, are resistant to multiple drugs. Pseudomonas aeruginosa, which is intrinsically resistant to a number of antimicrobial agents, is a leading cause of Gram negative, hospital acquired infections. Resistance to most antipseudomonal agents has increased by> 20%, over the last five years.[1] Carbapenems are used to treat serious infections, as a last resort, when the organism is resistant to the primary agents of choice. Emerging resistance to carbapenems limits therapeutic options. Therefore, periodic surveillance of the resistance pattern, within individual institutions, is critical for the selection of an appropriate, empiric antimicrobial agent. The present study was undertaken to determine the prevalence of carbapenem resistance among P. aeruginosa strains isolated from relevant clinical specimens. A prospective analytical study was undertaken from January 2004 to August 2004, in the Department of Clinical Microbiology, of a tertiary care medical centre. Patients, who developed infections after 48 h of being admitted to the hospital, were included in the study. Most patients received empiric ampicillin and gentamicin. Those with severe infections were started on a combination therapy of amikacin and cefotaxime. Patients, who had been admitted with prior infections, were excluded. Type of samples taken included blood, endotracheal aspirate, bronchial wash, intravenous catheters, and significant isolates from urine and wound swabs. Standard procedures were followed for identification.[2] Antibiotic sensitivity testing was done using the Kirby Bauer disc diffusion method, according to CLSI (Clinical Laboratory Standards Institute) guidelines. Minimum inhibitory concentration by the agar dilution method was done using Meropenem powder (source:AstraZeneca), as per CLSI guidelines. Standard ATCC P. aeruginosa 27853 was used for quality control. Twenty-nine, out of 266 (10.9%), isolates of P. aeruginosa were resistant to meropenem and imipenem. The MIC of meropenem for the resistant strains (n=26) ranged from 8 µg/ml to> 64 µg/ml. (Breakpoint MIC for P. aeruginosa - < 4 µg/ml to> 16 µg/ml). [Figure - 1] P. aeruginosa was predominantly isolated from catheterised patients and wound swabs from moribund patients (27%). Ten per cent of the isolates were from blood cultures and intravenous catheters. Twenty per cent of the isolates were obtained from respiratory infections as shown by endotracheal aspirate cultures. The distribution of resistant isolates was seen to be higher in patients admitted to the intensive care unit (62%), when compared to those in the non-intensive care areas such as general and special wards (38%). Twenty per cent of the resistant strains were sensitive to amikacin, 13% and 10%, each to piperacillin and cefepime, respectively and 3% to ciprofloxacin. [Figure - 2] Resistance to antimicrobial agents is an increasing clinical problem and a recognised public health threat. Among the organisms associated with infections in the hospital P. aeruginosa stands out for various reasons. It is ubiquitously found in the hospital environment and tends to remain viable on both animate and inanimate objects around the patient, including antiseptic solutions. Carbapenems are still the drug of choice for multi-drug resistant P. aeruginosa and extended spectrum beta lactamase producing organisms. This group of antibiotics is rapidly replacing cephalosporins and quinolones in the treatment of multi-drug resistant Gram negative bacteria. Carbapenems are also used to treat nosocomial and mixed bacterial infections. However, nosocomial isolates may easily develop resistance to carbapenems due to the reduced uptake of the drug, which leads to outbreaks of imipenem/ meropenem resistant strains. Imipenem resistance in Pseudomonas is considered to be associated with loss of the porin Opr D, combined with activity of chromosomal beta lactamase (Amp C), while overexpression of multi-drug efflux pumps is considered to confer meropenem resistance.[3] Outbreaks caused by multi-resistant P.aeruginosa have been reported in various nosocomial settings, such as intensive care units, within a hospital. Therefore, it is essential to be vigilant and monitor the resistance to this antibiotic. Studies have documented that the amount of aminoglycosides used in hospitals correlate with the development of aminoglycoside-resistant Enterobacteriaceae and P. aeruginosa .[4] In the present study, resistance to imipenem/ meropenem showed a prevalence rate of 10.9% among P. aruginosa isolates. The finding that imipenem carries a higher risk of emergence of resistance is consistent with the results of other studies. The clinical emergence of resistant P. aeruginosa has been described during imipenem therapy, ranging from 14% to 53%.[5] Another study by Taneja et al in 2003 showed 42% resistance to imipenem in urinary isolates.[6] In the present study, 27.6% of the isolates were obtained from wounds. P. aeruginosa has increasingly been isolated in surgical wound infections. The incidence of wound infections however varies from surgeon to surgeon, hospital to hospital, one surgical procedure to another and also from one patient to another. Endotracheal aspirate accounted for 20.7% of isolates showing indwelling devices as one of the major risk factors for the development of imipenem resistant P. aeruginosa in the present study. Another study by B.Cao et al showed previous exposure to imipenem/ meropenem and mechanical ventilation as being risk factors for multi-drug resistant Pseudomonas .[7] A majority of isolates were from ICU patients in the present study, which may be due to the high usage of indwelling catheters among patients who are admitted to the ICU. In the present study, amikacin and piperacillin sensitivity were 20.7% and 13.7%, respectively, in imipenem resistant P. aeruginosa . Therefore, amikacin and piperacillin may be used as alternative drugs in a limited number of cases. In randomised clinical trials, antibiotic resistance was significantly higher for imipenem than for ciprofloxacin or piperacillin-tazobactam.[8] Ciprofloxacin resistance was 97% among imipenem resistant P. aeruginosa in the present study. In the study by Taneja et al, piperacillin and amikacin had the best in vitro susceptibility.[6] A high rate of 10% strains of P. aeruginosa have developed in vitro resistance to carbapenem, within a short span of time, since the introduction of the antibiotic. This is the last resort for treatment of life threatening infections in hospital. Judicious use and constant monitoring are essential to check the spread of imipenem/ meropenem resistant P. aeruginosa in hospitals and its subsequent spread in the community. The use of imipenem for the treatment of P. aeruginosa should be reserved for situations where the infection is polymicrobial or for pseudomonas isolates resistant to other antibiotics. In cases where imipenem is selected as the antipseudomonal antibiotic, the potential for emergence of resistance should be anticipated. In appropriate circumstances, routine culture and susceptibility tests should be performed to detect the emergence of resistance to P. aeruginosa as early as possible. Attention by the hospital infection control team is essential to implement stringent preventive measures to contain the spread of the infection and promote the judicious use of antimicrobial agents. Antibiotic resistance is increasing at an alarming rate, leading to increased morbidity, mortality and treatment costs. A key factor in the development of antibiotic resistance is the inappropriate use of antibiotics. The medical fraternity needs to understand that antibiotics constitute a precious and finite resource. Unless conscious efforts are made to contain the menace of drug resistance, multi-drug resistant organisms, untreatable by every known antibiotic, may emerge, reversing the medical progress made by mankind and throwing us back to the pre-antibiotic era. References
Copyright 2006 - Indian Journal of Pharmacology The following images related to this document are available:Photo images[ph06076f2.jpg] [ph06076f1.jpg] |
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