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Indian Journal of Medical Sciences
Medknow Publications on behalf of Indian Journal of Medical Sciences Trust
ISSN: 0019-5359 EISSN: 1998-3654
Vol. 64, Num. 12, 2010, pp. 556-559

Indian Journal of Medical Sciences, Vol. 64, No. 12, December, 2010, pp. 556-559

Case Report

Ceftriaxone resistant Shigella flexneri, an emerging problem

Department of Microbiology, St. John's Medical College, Bangalore - 560 034, India

Correspondence Address:
Baijayanti Mishra
Department of Microbiology, St. John's Medical College, Bangalore- 560034, Karnataka

Code Number: ms10005

PMID: 21258157

DOI: 10.4103/0019-5359.75931


Shigellosis is a disease of public health importance in developing countries. It may cause self-limited diarrhea to severe dysentery. Emergence of multi drug resistant (MDR) strains is a growing concern globally. Ceftriaxone and ciprofloxacin are the drugs of choice for MDR cases. Here, we report a case of MDR Shigella flexneri from an immunocompromised patient. The strain was resistant to ceftriaxone [minimum inhibitory concentration (MIC) ≥ 64 μg/ml], limiting the treatment option. Simultaneously, the strain was also found to be resistant to ciprofloxacin (MIC ≥ 4 μg/ml). However, it was susceptible to ceftazidime (MIC 4 μg/ml). This is the first case of ceftriaxone resistant Shigella spp. reported from our hospital.

Keywords: Ceftriaxone, extended spectrum beta lactamase, minimum inhibitory concentration, multi drug resistant, Shigella flexneri


In the developing countries, shigellosis is an important public health problem. One hundred and forty million people suffer from shigellosis, with an estimated 600,000 deaths per year worldwide. [1] Shigella infections can lead to illness ranging from mild self-limiting diarrhea to severe dysentery with frequent passage of blood and mucus, high fever, cramps, tenesmus and in rare causes bacteremia. Complications of shigellosis are seen most frequently in children, the elderly and the immunocompromised. [2],[3] Prompt and appropriate therapy is necessary in shortening the duration of clinical symptoms as well as to prevent transmission of infection to close contacts. [4],[5] Emergence of multi drug resistant (MDR) Shigella is a growing concern globally, and in severe MDR shigellosis, ceftriaxone is an effective drug of choice. [5],[6] However, recently, there has also been emergence of ceftriaxone resistant strains, limiting the treatment option. [7],[8]

Case Report

A 61-year-old female with history of abdominal pain, vomiting, alternating constipation and loose stool, loss of appetite and weight, weakness and generalized body ache since last 3 months, with a worsening condition in last 1 week was admitted in our hospital. The patient had anemia, thrombocytopenia and investigation showed that the patient had blood cell leukemia. At admission, the patient had fever and was empirically started on ceftriaxone 2 g intravenous once daily.

The patient continued to pass loose stool with blood and mucus, which was sent for routine analysis, culture and sensitivity. Stool routine analysis showed the presence of 25-30 WBC/high power field (HPF) and 10-15 RBC/HPF. No ova, cyst and trophozoite were found. Stool cultures were set up on Xylose Lysine Decarboxylase media, Salmonella Shigella Agar, Mac Conkeys Agar and Selenite F Broth, and standard microbiological methods were followed.

The organism isolated from the stool culture was biochemically and serotypically (Denken-Seika, Japan Shigella antisera) identified as Shigella flexneri and was confirmed by VITEK 2C (bioMérieux, Marcy I'Etoile, France). Antibiotic susceptibility was determined by using Kirby-Bauer disk diffusion in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. The isolate was found to be resistant to ampicillin, cotrimoxazole, chloramphenicol, nalidixic acid, ciprofloxacin and ceftriaxone, and sensitive to meropenem, ceftazidime and pipercillin-tazobactum. The minimum inhibitory concentration (MIC) of different drugs were determined by using VITEK 2C (bioMérieux). The MIC of ceftriaxone was ≥64 μg/ml, showing high resistance, while the MIC of ceftazidime was 4 μg/ml, which was susceptible. Ciprofloxacin (MIC ≥ 4 μg/ml) was also found to be resistant. The extended spectrum beta lactamase (ESBL) detection was found to be positive for the given strain using double disk approximation test, so also by VITEK 2C.

Thus, even after administration of ceftriaxone, the patient was passing loose stool with blood and mucus and was bleeding per rectum with pain in lower abdomen. However, unfortunately, the patient got discharged against medical advice before the ceftriaxone resistant S. flexneri was reported and could not be followed up.


Diarrheal disease and enteric infections are major cause of morbidity and mortality in the developing world. [1],[2] Shigella still accounts for a significant proportion of bacillary dysentery in several tropical and subtropical countries. [2],[3] Though Shigella dysentery is a self-limiting infection, there is a need for antibiotic therapy not only to reduce the severity but also in reducing the transmission of infection.

MDR Shigella is being reported from many countries and this has made the selection of drugs complicated. The third-generation cephalosporins and fluorouinolones are the mainstay of treatment in MDR cases. However, resistance to third-generation cephalosporins, namely ceftriaxone resistance, is not uncommon in the Indian subcontinent. [6],[9] A study conducted by Godwin Wilson et al. in western Nepal showed Shigella isolates having MIC50 and MIC90 for ceftriaxone to be 16 and 32 μg/ml, respectively. [1]

Our hospital is a tertiary care hospital in Bangalore, receiving approximately 600 diarrheal and dysenteric stools per year. The percentage isolation of Shigella is around 5%. As per the prevalence of resistance pattern reported between 2002 and 2007, over 70% of Shigella isolates were resistant to two or more drugs including ampicillin and cotrimoxazole. Resistance rate of ampicillin was 55.3%, cotrimoxazole 81.3%, chloramphenicol 43.3%, nalidixic acid 61.9% and ciprofloxacin 20.9%. [7] No resistance to ceftriaxone was observed during the study period. This is the first case of ceftriaxone resistant Shigella from our hospital, showing a MIC of ≥64 μg/ml. This S. flexneri strain was simultaneously resistant to ampicillin, cotrimoxazole, chloramphenicol, nalidixic acid and ciprofloxacin. Though the strain was ceftriaxone resistant, it was sensitive to ceftazidime, showing a MIC=4 μg/ml by VITEK 2C (bioMérieux). This strain was also found to be sensitive to carbapenems and piperacillin-tazobactam. However, as the patient got discharged against medical advice before the reporting of ceftriaxone resistant S. flexneri, no appropriate therapy could be administered and there might be a chance of transmission in the close community.

Third-generation cephalosporin resistance is mediated by ESBLs. [6],[9] Studies have shown that SHV-3 like ESBL producing isolates are 100% resistant to ceftriaxone in vitro, but are only 50% resistant to ceftazidime. [8] The cephalosporin resistance can be attributed to the fact of use of ceftriaxone in the food of animals [4] or to its extensive use in clinical settings. In our case, the patient was on ceftriaxone only for a short period, and as the previous antibiotic treatment history was also not known, the possibility of acquiring this resistance remained unknown. Though phenotypic detection of ESBL was performed, we could not characterize this ESBL genotypically. In the phenotypic detection of ESBL, we noticed that clavulanic acid did not restore susceptibility to amoxicillin but did restore susceptibility to cefotaxime. Hence, it is recommended that third-generation cephalosporins, particularly ceftriaxone, should be kept in reserve and to be used only in case of proven drug resistant and non responsive cases. [3]

Emergence of cephalosporin resistant Shigella spp. is a growing concern as it poses a therapeutic challenge, and thus, there is a need to stop the widespread dissemination in community.


1.Wilson G, Easow JM, Mukhopadhyay C, Shivananda PG. Isolation and antimicrobial susceptibility of Shigella from patients with acute gastroenteritis in Western Nepal. Ind J Med Res 2006;123:145-50.  Back to cited text no. 1    
2.Mamatha B, Pusapati BR, Rituparna C. Changing pattern of antimicrobial susceptibility of Shigella serotypes isolated from children with acute diarrhea in manipal, South India, a 5 year study. Southeast Asian J Trop Med Public Health 2007;38:863-6.  Back to cited text no. 2  [PUBMED]  
3.Yismow G, Negeri C, Kassu A. A five year antimicrobial resistance pattern observed in Shigella species isolated from stool samples in Gondar University Hospital, Northwest Ethiopia. Ethiop J Health Dev 2006;20:194-8.  Back to cited text no. 3    
4.Sivapalasingam S, Nelson JM, Joyce K, Hoekstra M, Angulo FJ, Mintz ED. High prevalence of antimicrobial resistance among Shigella isolates in the United States tested by the national antimicrobial resistance monitoring system from 1999 to 2002. Antimicrob Agents Chemother 2006;50:49-54.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Ashkenazi S, Levy I, Kazaronovski V, Samra Z. Growing antimicrobial resistance of Shigella isolates. J Antimicrob Chemother 2003;51:427-9.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Rahman M, Shoma S, Rashid H, Siddique AK, Nair GB, Sack DA. Extended spectrum beta lactamase mediated third generation cephalosporin resistance in Shigella isolates in Bangladesh. J Antimicrob Chemother 2004;52:846-7.  Back to cited text no. 6    
7.Srinivasa H, Baijayanti M, Raksha Y. Magnitude of drug resistant Shigellosis: A report from Bangalore. Indian J Med Microbiol 2009;27:358-60.  Back to cited text no. 7  [PUBMED]  Medknow Journal
8.D'agata E, Venkataraman L, DeGirolami P, Weigel L, Samore M, Tenover F. The molecular and clinical epidemiology of Enterobacteriaceae producing extended spectrum beta-lactamase in a tertiary care hospital. J Infect 1998;36:279-85.  Back to cited text no. 8  [PUBMED]  
9.Sabir N, Zafar A. Cephalosporin resistant Shigella flexneri from a clinical isolate - a rare finding. J Pak Med Assoc 2005;55:560-1.  Back to cited text no. 9  [PUBMED]  

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