The Re-Emergence Of Chloramphenicol Sensitivity Among Enteric Fever Pathogens In MangaloreCorrespondence Address :
Yashavanth Rai, Dept. of Microbiology, A.J.I.M.S, Kuntikana, Mangalore-575004.
Enteric fever is a global health problem, especially in the developing countries of the tropics. Drug resistance among enteric fever pathogens is a major challenge for the clinicians. Since its introduction in 1948, chloramphenicol (C) remained as the drug of choice for enteric fever. Later, ciprofloxacin (Cf) replaced C, when C-resisitant enteric fever emerged and caused outbreaks in different parts of the world. Fluoroquinlones are replaced by third generation cephalosporins like ceftriaxone (Ci) and cefotaxime (Ce) as the first line therapy nowadays. C-sensitive Salmonella serotypes emerged again due to the withdrawal of antibiotic pressure. Therefore, an attempt was made to study the incidence of blood stream Salmonella infections and their antimicrobial susceptibility pattern.
Method: Strains isolated from 188 blood culture positive cases of enteric fever over a period of 1 year and 11 months were studied and their sensitivity pattern to chloramphenicol(C), ampicillin(A), cotrimoxazole(Co), nalidixic acid(Na), ciprofloxacin(Cf), ofloxacin(Of) and ceftriaxone(Ci) were analysed by the disk diffusion method according to the Clinical Laboratory Standard Institute(CLSI) guidelines. The Minimum Inhibitory Concentration (MIC) was determined for chloramphenicol by the agar dilution method according to the CLSI guidelines.
Results: A total of 188(2.99%) Salmonella isolates were obtained from blood culture during the period of 1 year and 11 months. Of these, 77 were S.typhi and 111 were S.paratyphi A. The present study showed higher chloramphenicol sensitivity for S.typhi (97.4%) and S.paratyphi A (100%). The MIC for Chloramphenicol was ≤ 4 Âµg/ml for 187 Salmonella isolates. One Salmonella isolate showed C - MIC of 64 Âµg/ml.
Conclusion: This study has shown the reemergence of chloramphenicol sensitivity among enteric fever pathogens. The results suggest the necessity for the reevaluation of chloramphenicol therapy in enteric fever.
Chloramphenicol, Disk-diffusion, Minimum Inhibitory Concentration, Salmonella
Enteric fever is a growing concern, worldwide. The World Health Organisation (WHO) estimates that there are about 22 million cases of enteric fever worldwide, every year (1). Enteric fever continues to be endemic in all parts of India. Salmonella typhi and Salmonella paratyphi A are predominant types of Salmonella which are responsible for the incidence of enteric fever in India (2). Chloramphenicol had been the â€śgold standardâ€ť therapy since its introduction in 1948. In India, drug resistance to S.typhi has been reported since 1960, followed by the first outbreak of multidrug resistant S.typhi (MDRST) in Calicut (3). Since then, MDRST has appeared throughout the world, especially in South America, the Indian subcontinent, Africa and South East Asia [4, 5]. Resistance to commonly used antibiotics such as chloramphenicol, ampicillin and cotrimoxazole has been reported from different parts of India in the last two decades. Fluoroquinolones emerged as the drug of choice for the treatment of enteric fever. There have been increasing cases of clinical failure after the administration of ciprofloxacin (Cf) to patients with enteric fever (6). Third generation cephalosporins like ceftriaxone and cefotaxime are being used as the first line therapy in the treatment of enteric fever now- a -days (7).
In this scenario, reports of the reemergence of the sensitivity of S.typhi and S.paratyphi A to chloramphenicol calls for a reappraisal of the antibiotic sensitivity pattern of the strains which are prevalent in India. The aim of this study was to analyse the drug sensitivity pattern of blood culture positive cases of enteric fever.
A total of 6297 specimens were received for blood culture during the study period (August 2005-June 2007), at a tertiary care hospital in Mangalore. All the blood culures were performed by using the BacT- Alert automated blood culture system. The isolates obtained, were identified, based on standard laboratory techniques (8).
Anitbiotic susceptibity of the isolates were determined against 7 antibacterial agents by the Kirby Bauer disk diffusion method. They included ampicillin [10Âµg], chloramphenicol [30 Âµg], ceftriaxone [30 Âµg], ciprofloxacin [5 Âµg], cotrimoxazole [25 Âµg], nalidixic acid [30 Âµg] and ofloxacin [5 Âµg] [Hi-media Mumbai]. Minimum Inhibitory Concentration [MIC] was determined for chloramphenicol by the agar dilution method. The results were recorded and interpreted as per the recommendations of the CLSI (9).
A total of 188 [2.99%] Salmonella isolates were obtained from 6297 blood cultures. Of these, 77 were S.typhi and 111 were S.paratyphi A.
(Table/Fig 1) shows the antibiotic sensitvity pattern of S.typhi and S.paratyphi A. These results show a high sensitivity of S.typhi [97.4%] and S.paratyphi A [100%] to chloramphenicol. Among the S.typhi isolates, susceptibility was found to be 99.87% for ampicillin, 97.4% for cotrimoxazole, 23.4% for nalidixic acid and 100% for ciprofloxacin, ofloxacin and ceftriaxone.
Among 111 S.paratyphi A isolates, susceptibility was found to be 92.79% for ampicillin and 100% for cotrimoxazole, ciprofloxacin, ofloxacin and ceftriaxone. All S.paratyphi A strains were found to be resistant to nalidixic acid by the disk diffusion method.
The MIC of Chloramphenicol was ≤4 Âµg/ml for 187 Salmonella isolates. One Salmonella isolate showed an MIC of 64Âµg/ml by the agar dilution method. This isolate showed multidrug resistance (to A, Co and C by the disk diffusion method).
Enteric fever continues to be a major public health problem in our country, being compounded by the emerging resistance to antibiotics that were effective earlier. Wide variations in different geographical regions in India make it necessary to ensure the sensitivity of the enteric fever pathogen to antibiotics before instituting therapy.
Chloramphenicol was the first antibiotic which was used against typhoid and resistance to this drug developed in the seventies and eighties and thereafter, to the other first line drugs like trimethoprim, sulfamethaxazole and ampicillin. In the nineties, increasing resistance to ciprofloxacin which was a good alternative for the multidrug resistant enteric fever pathogen emerged in both S.typhi and S.paratyphi A (10). Resistance to ceftriaxone has also been reported (11).
In India, there have been varying reports on the resistance of S.typhi and S.paratyphi A to various antibiotics [12,13]. There have been reports of the reemergence of the sensitivity of S.typhi and S.paratyphi A to chloramphenicol and other first line drugs (14). The present study showed 97.4% sensitivity to chloramphenicol in S.typhi and 100% sensitivity in S.paratyphi A. The MIC of Chloramphenicol was ≤4 Âµg/ml for 187 Salmonella isolates; only one isolate had an MIC of 64Âµg/ml by the agar dilution method. These results are very similar to other reports from other parts of India and point towards the re-emergence of the sensitivity to chloramphenicol in this region also [14, 15].
The significant decrease in chloramphenicol resistant Salmonella isolates in Bangladesh suggested the cheaper and the effective first line antibiotic, chloramphenicol, as the drug of choice for the treatment of enteric fever (16).
The previous generation antibiotics are increasingly being found to be useful for the treatment of many diseases. Chloramphenicol can be a useful and cost effective alternative in selected cases. Consistent surveillance and antibiotic susceptibility testing is required in different parts in the country to know the antibiotic sensitivity pattern among enteric fever pathogens. There is a possibility that restricted use can lead to the withdrawal of selective presssure and resistant bacteria will no longer have the advantage of survival in such settings.
Source of support: The authors are grateful to Manipal University for providing financial support for the research project.
Conflict of interest: NO
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