B-lactam Antibiotics Resistance Pattern and its Development in Indigenous Clinical Isolates

Abstract

The emergence of resistance to antimicrobial agents is a global public health problem. Although a number of factors can be identified which contribute to this problem, /3- lactamases of Gram-negative bacteria are the most important mechanism of resistance against /3-lactam drugs . This study was carried out to evaluate the prevalence of the infection and the development of resistance in clinically significant bacteria against commonly used antibiotics with special reference to /3-lactam agents. In addition, the study was also aimed to determine the frequency of Extended-Spectrum /3-Lactamase (ESBL) production among Enteric Gram-negative rods (EGNRs) and their sensitivity pattern as well. A total of 971 2 samples, received in the Clinical Microbiology Laboratory of Fauji . Foundation Hospital, Rawalpindi during April 2004 to March 2006, both fi'om in-patients and out-patients, were processed and subjected to culture and sensitivity, followed by ESBL detection by Double Disk Diffusion Synergy Test. The incidence of bacterial infection was 43.3%. The Gram- negative rods (GNRs) were most prevalent (57.5%) followed by Gram-positive cocci (40.1 %). Staphylococcus aureus (32.6%) was most prevalent organism, followed by Escherichia coli (24.7%) and Pseudomonas aeruginosa (15.9%). The frequency ofESBL in Gram-negative rods was 38.9%. The most common ESBL producing EGNR was E. coli (47.5%) followed by K. pneumoniae (45.0%). Highest resistance of ESBL-producing E. coli was noted against 3rd generation cephalosporins {ceftazidime (97.1 %), cefotaxime (97.2%)}, followed by aztreonam (96.1 %), co VIII Abstract IX trimoxazole (89.9%), piperacillin/tazobactam (21.1 %) and imipenem (1.9%). Similar pattern of resistance was noted for ESBL-producing K. pneumoniae ceftazidime (96.8%), cefotaxime (98.1 %), followed by aztreonam (92.2%), ciprofloxacin (89.6%), gentamicin (89.1 %), piperacillin/tazobactam (9.1 %) and imipenem (3.1 %). The sensitivity of ESBLs-producing K. pneumoniae and E. coli was reduced not only towards 3rd generation cephalosporins but cross-resistance was noted against other antibiotics as well like co-trimoxazole, doxycycline, co-amoxiclav, norfloxacin and gentamicin. Carbapenems, /3-lactaml /3-lactamase inhibitors and fosfomycin were found most effective against both ESBL-producing and ESBL non-producing Gram negative rods. In conclusion, considerable resistance was demonstrated amongst the isolated organisms against all the commonly used antibiotics including /3-lactams. So it is important to avoid the misuse of antibiotics, as well as to screen for ESBLs routinely by all the laboratories. If an isolate is found to be an ESBL-producer, it should be considered resistant to all lactam drugs including third generation cephaolosporins and aztreonam. Administration of these antibiotics as an empirical therapy could be disastrous in these cases because these would not only be ineffective thus causing increased mortality but would also promote the ESBL-production. The best empirical therapy for these cases would be carbapenems, /3-lactam /3-lactamase inhibitor combinations and fosfomycin. On the other hand, regarding ESBL non-producer, most of the conventional cheap antibiotics would be effective to combat the infection.