Recent trend of multi-drug resistance in Pseudomonas aeruginosa

Introduction: P. aeruginosa is a ubiquitous and versatile human opportunistic pathogen and has implications on morbidity, mortality and healthcare costs both in hospitals and in the community1. Infections caused by P.aeruginosa are frequently life-threatening and difficult to treat as it exhibits intrinsically high resistance to many antimicrobials and the development of increased multi-drug resistance in health care settings2,3. Mechanisms that cause antimicrobial drug resistance and multi-drug resistance in P.aeruginosa are due to acquisition of resistance genes (e.g those encoding beta-lactamase4 and amino-glycoside modifying enzymes5 via horizontal gene transfer and mutation of chromosomal genes (target site, efflux mutations) are the target of the fluoro-

quinolones particularly ciprofloxacin 6 .This pathogen is intrinsically resistant to most antibiotics such as, chloramphenicol, tetracycline, macrolides, trimethoprim-sulfamethoxazole, and rifampin 7 .Resistance in P. aeruginosa may be due to outer membrane modifications, production of extendedspectrum beta-lactamase and efflux pumps, which confers various levels of resistance to expanded spectrum cephalosporins 8,9 .Biofilm formation in P.aeruginosa, particularly in the case of pulmonary infections in patients with cystic fibrosis, contribute to its resistance to antimicrobial agents 10 .Hypermutable strains of P.aeruginosa exhibiting increased mutation rates are common in chronic infections such as those that occur in the lungs of cystic fibrosis patients 11 .Increase in the frequency of multi-drug resistant (MDR) strains of P.aeruginosa has severely limited the availability of therapeutic options.Data on antimicrobial susceptibility profiles of P. aeruginosa is limited in Nepal 12,13 .Therefore, this study was thus designed to find out the current antimicrobial resistance patterns of P.aeruginosa strains in Nepalese patients at mid and far western region of Nepal.

Material And Methods: Study background and subjects
This was a Retrospective study conducted on 917 Nepalese patients, attending outpatients and inpatients departments of Nepalgunj Medical College and teaching Hospital, Banke, Nepal, between September 2011 and January 2014.

Statistical analysis
Data obtained were analyzed using the SPSS (v.16.0) Chicago, U.S.A. Association of gender and age-groups of P. aeruginosa was assessed using chisquare test.P values <0.05 were considered to be statistically significant.

Results:
194 strains of P. aeruginosa were isolated and identified out of a total of 917 clinical specimens investigated.Sputum, Wound/pus, urine, tracheal aspirates and vaginal Swab (173, 89.18%) were the predominant sources of specimens of P.aeruginosa clinical isolates as depicted in Table 1.The rate of isolation of P. aeruginosa was 21.16 %.Of these 194 strains of P. aeruginosa, 112 (57.73%) were from female and 82 (42.27%) were from male.P. aeruginosa were isolated from patients aged between 1 and >60 years.A high prevalence (45.36%) of P. aeruginosa was identified in subjects aged 21-40 years and this age group was statistically significant (P<0.05),compared to the other age groups.However, there was no significant difference in the overall prevalence of isolates according to sex as shown in Table 2.

Antimicrobial susceptibility patterns
Antimicrobial susceptibility patterns of P.aeruginosa varied markedly with the antibiotic tested.P.aeruginosa isolates showed maximum resistance to chlo- Similarly, in other study of Nepal larger female group was also found [16 . Ahmed et al. 20 reported an increased incidence in male (77.7%) as well as a higher prevalence rate among elderly 61-80 years (43.92%).Increasing resistance to different antipseudomonal drugs particularly among hospital strains has been reported world-wide 21-24 and this is a serious therapeutic problem in the management of disease due to these organisms.The resistance profiles of P. aeruginosa to a panel of fifteen antimicrobial agents tested varied among the isolates investigated.In the present study, an overall high rate of resistance was observed to chloramphenicol, ceftriaxone, Cefepime, Cefoperazone-Salbactum and co-trimoxazole.The maximum resistant isolates were observed in age group 21 -40 and >60.One striking feature in this study was that all the P. aeruginosa isolates were found to be sensitive to imipen-   Results of the present study clearly demonstrated the occurrence of resistance to various antipseudomonal agents among the P. aeruginosa isolates and the observed rate of multi-drug resistance was 24.74% which was more or less similar to the other recent study conducted in Nepal 13,16 and Malaysia 25 .The emergence of resistance to many drugs, as flouroquinolones and third generation cephalosoprins, semi-synthetic penicillin with beta-lactamase inhibitors, in P.aeruginosa strains is a cause of great concern not only at local and regional level, but also in a national and international scale.The culture of antimicrobial abuse needs to be soon stopped.Continuous surveillance of multidrug resistant strains is very important to know the changing antibiotic susceptibility patterns from time to time.A network of laboratories for real time monitoring of antibiotic resistance of P. aeruginosa and timely dissemination of such information to the clinicians for modification of treatment strategy are urgently necessary to prevent the emergence of multi-drug resistant strains of P. aeruginosa.

Table 3 .
Multi-drug resistance of P.aeruginosa isolates in different classes of antibiotics is shown in Table4.

Table 4 : Multi-drug resistance P. aeruginosa isolates em
whereas meropenem showed 7.73% resistance.This may be due to the restricted use of imipenem in this hospital.This is consistent with a report published in 2013 in Nepal 16 .