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The 3<sup>rd</sup> International Conference on Drug Discovery & Therapy: Dubai, February 7 - 11, 2011

Recent Advances in Patient Treatment and Care (Track)

High-level Ciprofloxacin Resistance in Shigella species in Urban and Rural Bangladesh: Implication for therapy

M. Anowar Hossain
Clinical Laboratory Services International Centre for Diarrhoeal Disease research, Bangladesh (ICDDR,B)

Abstract:

Background and aims: Infection due to Shigella is a global public-health problem associated with significant morbidity, mortality, economic and health burden in developing countries, including Bangladesh. Emergence and spread of multidrug-resistant Shigella spp causes treatment failures and limits the empiric therapy. We reviewed the results of stool cultures to observe the pattern of Shigella-associated infection in diarrhoeal patients of all ages and gender who were either hospitalized at urban Dhaka and rural Matlab hospitals of ICDDR,B or referred cases from public or private hospitals and clinics in and around Dhaka city between 2001 and 2009 and examined the pattern of antimicrobial resistance of the isolates.

Materials and methods: Briefly, stools or rectal swabs obtained from diarrhoeal patients were processed for enteric pathogens including Shigella following standard methods. Shigella spp were identified by characteristic colony morphology, confirmed biochemically and serologically by slide-agglutination tests using polyvalent group and type-specific commercial antisera. Antimicrobial susceptibility was performed by disc-diffusion method following the CLSI guideline against five antimicrobials including ciprofloxacin. The phenotype pattern of resistance was determined and the MIC was performed on selected isolates using E-test.

Results: Among 125,539 diarrhoeal patients from Dhaka, Shigella spp were isolated from 9,133 cases (7.3%) and among 15,045 stool specimens in Matlab, Shigella were yielded from 1,401 cases (9.3%). Of the isolates, Shigella flexneri was the most common strain identified both in Dhaka (61.3%) and Matlab (71.4%) followed by S. boydii and S. sonnei. Again, S. flexneri was the species that was most commonly resistant to ciprofloxacin. Only 4 strains of ciprofloxacin-resistant S. dysenteriae type 1 were reported from both locations and no Sd1 was isolated in Matlab after May 2003 and in Dhaka after October 2004. Regardless of resistance to ampicillin, co-trimoxazole, nalidixic acid, mecillinam and ciprofloxacin, species and location, 92.8% strains were resistant to multiple antimicrobials, which was defined an isolate resistance to more than two drugs. The multiple drug-resistance strains are spreading across various species of Shigella. Phenotype pattern showed that 15.7% of isolates were resistance to 5 drugs, 49.2% to 4 drugs and 27.9% to 3 drugs. The proportion of strains that were resistant to ciprofloxacin increased in Dhaka and Matlab from near 0% in 2005 25% in 2009. All ciprofloxacin resistant strains in Dhaka and Matlab had a minimum inhibitory concentration (MIC) ≥32 µg/ml. Among patients with strains of multiple drug-resistant Shigella 77.5% were children less than five years and 58.2% were male.

Discussion and conclusion: This rapid increase of multi-drug resistance may be due to wide spread use of ciprofloxacin available over-the counter for treating human diseases, as well as widespread use in agricultural sector, has conferred a survival advantage to Shigella strains. High levels of drug resistance limit the safe and efficacious treatment options for shigellosis, particularly in children. It thus warrants the need of antimicrobial policy to ensure their prudent use by healthcare providers. It also highlights the need to develop newer classes of antibiotics to treat shigellosis cases that are orally effective against Shigella species and other highly resistant enteric pathogens. A concerted effort by drug producers is required for the development of new effective drugs in parallel with the effort to develop an vaccine to contain the disease and limit the threat to public health.

Keywords: Diarrhoea, dysentry, Shigella, Resistance