Indian Journal of Medical Microbiology Home 

CASE REPORT
[Download PDF]
Year : 2013  |  Volume : 31  |  Issue : 1  |  Page : 77--79

Cefotaximase and AmpC-producing Shigella flexneri in case of dysentery from southern India

S Oommen, PM Sivan Pillai, S Sushamabai, P Jose Paul 
 Department of Microbiology, Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, Kerala, India

Correspondence Address:
S Oommen
Department of Microbiology, Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, Kerala
India

Abstract

Diarrhoea and dysentery caused by Shigella spp. are major public health concerns. Emerging multidrug resistance (MDR) in this pathogen further complicates this disease. Extended spectrum β-lactamases (ESBLs) have been described in this pathogen, which significantly compromises the treatment options for shigellosis. The usual ESBLs seen are sulfhydryl variable (SHV)-type; cefotaximases (CTX-M) are very uncommonly detected. Here, we report a CTX-M type and AmpC-producing Shigella flexneri from a three-year-old boy residing in Central Kerala, South India.

How to cite this article:
Oommen S, Sivan Pillai P M, Sushamabai S, Paul P J. Cefotaximase and AmpC-producing Shigella flexneri in case of dysentery from southern India.Indian J Med Microbiol 2013;31:77-79

How to cite this URL:
Oommen S, Sivan Pillai P M, Sushamabai S, Paul P J. Cefotaximase and AmpC-producing Shigella flexneri in case of dysentery from southern India. Indian J Med Microbiol [serial online] 2013 [cited 2019 Nov 22 ];31:77-79
Available from: http://www.ijmm.org/text.asp?2013/31/1/77/108734

Full Text

 Introduction



Presentation of shigellosis may range from mild self-limiting diarrhoea to severe dysentery with frequent passage of blood and mucus, high fever, cramps, tenesmus and dehydration. Complications of shigellosis like bacteremia, haemolytic uraemic syndrome, rectal prolapse, toxic megacolon and Reiter's syndrome [1] are seen most frequently in children, the elderly and immuno-compromised patients. Prompt and appropriate therapy is necessary in shortening the duration of clinical symptoms, as well as to prevent transmission of infection to close contacts. Emergence of multidrug-resistant (MDR) Shigella spp. (i.e., resistance to more than two first-line oral drugs, such as ampicillin, co-trimoxazole, ciprofloxacin) is of a growing concern globally. [2],[3] The drug of choice for the treatment of severe infections with these MDR strains is ceftriaxone. [2],[3] With the emergence of extended spectrum β-lactamase (ESBL)-producing strains, even ceftriaxone is ineffective, drastically limiting the treatment options for this bacterium. Here, we report a cefotaximases (CTX-M) like type ESBL and AmpC-producing Shigella flexneri from Central Kerala, India.

 Case Report



A 3-year-old male presented in a state of profound shock due to dehydration. A venous cut down was performed to administer intravenous fluids to stabilise his vitals. His mother gave a history of fever, severe abdominal pain and loose stools with blood. There was a history of consuming food and fruit juice from a wayside stall one day prior to the onset of illness. Stool was sent for culture and routine analysis and the patient was empirically treated with ceftriaxone, 100 mg/kg iv 24 hourly and metronidazole.

Stool routine analysis showed the presence of >30 white blood cells/high power field (WBCs/HPF). No ova, cyst and trophozoites were found. Stool cultures were carried out as per standard microbiological procedures and revealed the growth of Shigella spp. by conventional biochemicals [4] The isolate was further confirmed to be S. flexneri by serological agglutination testing (Denka-Seiken, Japan Shigella antisera).

Antibiotic susceptibility was determined by using Kirby-Bauer disc diffusion in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. [5] The isolate was found to be resistant to ampicillin, co-trimoxazole, chloramphenicol, nalidixic acid (zone diameter of 6 mm each), ciprofloxacin (15 mm) and sensitive to azithromycin (19 mm), tetracycline (18 mm), ceftazidime (24 mm) with no increase of zone diameter after addition of clavulanic acid, imipenem (27 mm) and meropenem (24 mm). Cefotaxime/ceftriaxone was intermediately sensitive with a zone diameter of 24 mm alerting the presence of CTX-M type ESBL.

The presence of CTX-M type ESBL was confirmed phenotypically using cefotaxime and cefotaxime+clavulanic acid disc diffusion method; an increase in ≥5 mm zone size for the cefotaxime+clavulanic acid disc was observed. The minimum inhibitory concentration (MIC) of different drugs was determined using VITEK 2C (bioMérieux, France). The MIC of ceftriaxone was ≥64 μg/ml, showing high resistance, whereas the MIC of ceftazidime was <1 μg/ml. Ciprofloxacin (MIC, ≥4 μg/ml), ampicillin (MIC, ≥32 μg/ml), co-trimoxazole (MIC, ≥4/76 μg/ml) were also found to be resistant. MIC of imipenem and meropenem was ≤1 μg/ml. VITEK 2C reported the strain as an ESBL (Cefotaximase) and AmpC-producing Shigella spp.

Even on the 3 rd day of starting ceftriaxone, the patient continued to be symptomatic with bloody stools, fever and severe pain in lower abdomen. Ceftriaxone was then substituted with meropenem for three days. The patient's condition improved and was discharged on oral azithromycin.

 Discussion



MDR Shigella is being reported from many countries and this has made the selection of drugs complicated. Third-generation cephalosporins are the mainstay of treatment in MDR cases. Cases of ESBL-producing Shigella spp. have been published from other parts of the Indian subcontinent [6],[7],[8] but not from Kerala. AmpC-producing Shigella spp. is comparatively rare and only a few cases have been reported from other parts of the world like Iran and Taiwan [9],[10] and from northern India [8] but this to the best of our knowledge is the first reported case of a combined AmpC- and ESBL-producing S. flexneri from South India.

One of the mechanisms of resistance to third-generation cephalosporin's is mediated by ESBLs. Inspite of definitive CLSI guidelines, resistance to ceftazidime is the key parameter used to detect ESBL in most routine laboratories till date. Inclusion of cefotaxime+clavulanic acid along with cefotaxime helps in detecting cefotaximase type of ESBL producing organisms Phenotypic confirmation of our isolate was carried out by VITEK 2C, which also detected the presence of an AmpC production by the strain. AmpC β-lactamases, in contrast to ESBLs, hydrolyse broad and extended spectrum cephalosporins and are not inhibited by β-lactamase inhibitors. This coupling of ESBL along with AmpC production with the persistence of symptoms made carbapenems the drug of choice in this case. Though molecular detection techniques are the gold standard for identifying ESBL/AmpC or carbapenemase genes, not many laboratories in our country can boast of offering these tests as a daily diagnostic tool for identification of these resistance mechanisms. Meanwhile, various studies for the detection of the same by VITEK 2C [11],[12] have shown a good sensitivity (98.1%), positive predictive value (99.3%), specificity (99.7%) and negative predictive value (99.3%) making it an acceptable alternative.

Drug-resistant Shiga bacillus is highly likely to spread further resulting in possibility of encountering more such cases in clinical practice in the near future and will certainly pose a major therapeutic challenge. An outbreak of shigellosis by such strains or the widespread dissemination of these resistant strains in overcrowded communities and popular tourist destinations like Kerala will prove to be a tough challenge in the containment of the disease. With the identification of ESBL/AmpC type of resistance in this bacteria and its spread, even ceftriaxone cannot be used as the first-line drug for severe cases of Shigella dysentery.

Surveillance and awareness of the emergence of resistance and reporting of these cases are imperative. Though the incidence of resistance is rare, screening of ESBL and AmpC must be considered upon isolation of Salmonella/Shigella isolates, which would help in reducing the morbidity and mortality associated with the disease. Meanwhile, the use of azithromycin rather than ceftriaxone as an empiric antibiotic for cases of severe dysentery prior to culture and sensitivity results may be considered in areas where MDR strains are reported to minimise the morbidity associated with the disease.

References

1Keusch GT, Kopecko DJ. Shigellosis. In: Fauci AS, editor. Harrison's Principles of Internal Medicine. 17 th ed., Ch. 138. New York: McGraw-Hill; 1997. p. 902-6.
2Rahman 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;54:846-7.
3Varsano I, Eidlitz-Marcus T, Nussinovitch M, Elian I. Comparative efficacy of ceftriaxone and ampicillin for treatment of severe shigellosis in children. J Pediatr 1991;118:627-32.
4Duguid JP. Shigella. In: Collee JG, Fraser AG, Marmion BP, Simmons A, editors. Mackie and McCartney Practical Medial Microbiology. 14 th ed., Ch. 22. New York: Churchill Livingstone; 1996. p. 405-12.
5Performance Standards for Antimicrobial Susceptibility Testing; 20 th Informational Supplement, Clinical and Laboratory Standards Institute (CLSI). M100-S22, Vol. 32, No. 3. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.
6Varghese SR, Aggarwal A. Extended spectrum beta-lactamase production in Shigella isolates: A matter of concern. Indian J Med Microbiol 2011;29:76-8.
7Gupta S, Mishra B, Muralidharan S, Srinivasa H. Ceftriaxone resistant Shigella flexneri, an emerging problem. Indian J Med Sci 2010;64:553-6.
8Taneja N, Mewara A, Kumar A, Verma G, Sharma M. Cephalosporin-resistant Shigella flexneri over 9 years (2001-09) in India. J Antimicrob Chemother 2012;67:1347-53.
9Tajbakhsh M, García Migura L, Rahbar M, Svendsen CA, Mohammadzadeh M, Zali MR, et al. Antimicrobial-resistant Shigella infections from Iran: An overlooked problem? J Antimicrob Chemother 2012;67:1128-33.
10Huang IF, Chiu CH, Wang MH, Wu CY, Hsieh KS, Chiou CC. Outbreak of dysentery associated with ceftriaxone-resistant Shigella sonnei: First report of plasmid-mediated CMY-2-type AmpC beta-lactamase resistance in S. sonnei. J Clin Microbiol 2005;43:2608-12.
11Spanu T, Sanguinetti M, Tumbarello M, D'Inzeo T, Fiori B, Posteraro B, et al. Evaluation of the new VITEK 2 extended-spectrum beta-lactamase (ESBL) test for rapid detection of ESBL production in Enterobacteriaceae isolates. J Clin Microbiol 2006;44:3257-62.
12Chen HM, Wu JJ, Tsai PF, Wann JY, Yan JJ. Evaluation of the capability of the VITEK 2 system to detect extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates, in particular with the coproduction of AmpC enzymes. Eur J Clin Microbiol Infect Dis 2009;28:871-4.