R A Corrigan and M M Raza Milton Keynes Hospital NHS Founda:on Trust, UK PURPOSE
CASE REPORT
DISCUSSION
This case report highlights a case of relapse of azithromycin resistant S. paratyphi A bacteraemia. It illustrates the changing suscep:bility paEern of Salmonella and the importance of suscep:bility tes:ng to guide therapy for imported cases of enteric fever.
We report the case of a 27 year old gentleman from India who was re-‐admiNed to our hospital with fevers. He had been admiNed 6 weeks before with a febrile illness, having just arrived from India to work in the UK. His blood cultures grew Salmonella paratyphi Type A. and liver func2on was mildly deranged. The isolate was sensi2ve to ampicillin, trimethoprim and third genera2on cephalosporins but resistant to azithromycin and ciprofloxacin. Ini2ally he was treated with IV ceSriaxone but his fever was slow to defervesce. Subsequently azithromycin was added but stopped in view of resistance. His fevers and CRP normalised and he went on to complete 2 weeks of IV ceSriaxone. His stool sample from this admission was nega2ve for Salmonella. On readmission 6 weeks later he was once again febrile with blood cultures growing the same organism sugges2ng a relapse. He was commenced on IV ceSriaxone once more along with oral co-‐trimoxazole. Stool and urine cultures were once again nega2ve for Salmonella. Of note abdominal ultrasound revealed gallstones although he had no abdominal symptoms and liver func2on was normal on this admission. His HIV serology was nega2ve and his fever resolved within 48 hours. This pa2ent was treated with IV ceSriaxone for 2 weeks and oral co-‐trimoxazole for 4 weeks in order to reduce the risk of carriage in view of the gallstones.
Resistance of Salmonella species to chloramphenicol, co-‐ trimoxazole, and ampicillin (defined as mul2drug resistance) as well as reduced suscep2bility and resistance to ciprofloxacin is well documented. In addi2on, raised MICs of azithromycin in rela2on to S. typhi and paratyphi A, including treatment failure with azithromycin has been reported3. Escherichia coli may be a reservoir for macrolide resistant genes and may cause azithromycin resistance in Salmonella through plasmid exchange5. Current Bri2sh Society for An2microbial Chemotherapy (BSAC) suscep2bility guidelines provide disc suscep2bility guidance for azithromycin for S. typhi only but no definite MIC guidance. However others have suggested a breakpoint MIC of 16 mg/liter for wild type Salmonella isolates.
BACKGROUND Imported cases of both S. typhi and paratyphi con2nue to increase in the United Kingdom par2cularly from the Indian subcon2nent. Mul2drug resistance is a well-‐recognized problem1. Resistance to fluoroquinolones is common and has led to the use of azithromycin as a first line agent2. However no agreed breakpoints for suscep2bility have been available un2l recently and there have been reports of azithromycin resistance3. Relapse of infec2on is associated with various risk factors, including gallstones4. Contact:
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References 1. An:microbial suscep:bility of Salmonella enterica serovars in a ter:ary care hospital in southern India Choudhary A et al. Indian J Med Res. Apr 2013; 137(4): 800–802. 2. Azithromycin for trea:ng uncomplicated typhoid and paratyphoid fever (enteric fever). Effa EE, Bukirwa H. Cochrane Database Syst Rev. 2008 Oct 8;(4). 3. First Report of Salmonella enterica Serotype Paratyphi A Azithromycin Resistance Leading to Treatment Failure. Molloy et al. J Clin Microbiol. Dec 2010; 48(12): 4655–4657. 4. Common bile duct stones: a cause of chronic salmonellosis. Lai CW et al. Am J Gastroenterol. 1992 Sep;87(9):1198-‐9. 5. Escherichia coli as Reservoir for Macrolide Resistance Genes Minh Chau Phuc Nguyen et al. Emerg Infect Dis. Oct 2009; 15(10): 1648–1650.
CONCLUSION PaEerns of Salmonella drug resistance are changing. The strain in this case was mul2drug resistant, resistant to newer an2bio2cs but sensi2ve to older an2bio2cs. Azithromycin resistance should be rou:nely tested. However, it does not always form part of commonly used automated systems. Gallstones are a risk factor for relapse of enteric fever. They increase the risk of carriage and impair eradica2on. Cholecystectomy may be required.