A gastrointestinal problem

History 68-year-old male attends an orthopaedic clinic as an emergency with a 3-day history of general malaise and fevers Family practitioner is concerned as the patient was discharged 1 week ago following methicillin-sensitive Staphylococcus aureus joint infection of prosthetic left hip after revision surgery for recurrent dislocations

History (cont’d) Total of 6-week treatment with flucloxacillin: First 2 weeks at a dose of 2 g 6-hourly IV followed by Four weeks at a dose of 1 g 6-hourly orally Good recovery and off antibiotics at discharge Family practitioner had started erythromycin 250 mg 6-hourly 3 days ago, but symptoms are getting worse Patient has had three episodes of loose bowel motions over the last 2 days, but not frank diarrhoea

Examination Hip wound appears slightly red but healed and there is no discharge Left hip not painful Lower abdomen slightly tender, otherwise gastrointestinal tract examination normal Clinical examination otherwise unremarkable Pulse 96 beats/minute; BP 145/90 mmHg Temperature 38.2°C WBC count 16.5 x 109/L (normal range 4.5–11.0 x 109/L) CRP 76 mg/L (normal range <10 mg/L) BP, blood pressure; CRP, C-reactive protein; WBC, white blood cell

What is your diagnosis? Relapse of hip infection Viral gastroenteritis Bacterial gastroenteritis Antibiotic-associated diarrhoea Irritable bowel syndrome Diverticulitis Perforation of bowel Obstruction of bowel Other

Initial tests and treatment Ultrasound of left hip joint showed no fluid collection X-ray of abdomen is normal

What specimen(s) would you collect now? Blood culture Faeces sample for culture and microscopy Hip aspirate for culture and microscopy Haemoglobin and blood cell counts Urea and electrolytes Liver function test All/several Other

Which pathogen(s) would you suspect? S. aureus Coagulase-negative staphylococci Gram-negative pathogens Mycobacterium tuberculosis Salmonella spp. Shigella spp. Campylobacter spp. Clostridium difficile Other

What antibiotic regimen (if any) would you prescribe initially? IV flucloxacillin IV third-generation cephalosporin IV ciprofloxacin IV glycopeptide Piperacillin/tazobactam Meropenem One of the above plus metronidazole One of the above plus an aminoglycoside Other

Treatment Diagnosis was relapse of hip infection Treatment started with flucloxacillin 2 g 6-hourly IV

Follow-up Overnight, the patient started to have profuse watery diarrhoea Abdominal pain increased Patient remained febrile WBC count next morning 27.6 x 109/L (normal range 4.5–11.0 x 109/L) Laboratory report of positive test for C. difficile toxin in the faeces

Which faeces test does your institution use for C Which faeces test does your institution use for C. difficile associated diarrhoea (CDAD)? Tissue culture for cytotoxin detection Culture for the organism Toxin immunoassay detection Gene detection Other Do not know

Laboratory testing for C. difficile No single test is accurate or reproducible A compromise solution to C. difficile infection testing is to use a two-step algorithm: Step 1. Glutamate dehydrogenase (or nucleic acid amplification test) to allow detection of colonised patients Step 2. Toxin detection by any appropriate method If Step 1 is positive and Step 2 is negative, then retest as ‘at risk’ Debast SB, et al. Clin Microbiol Infect 2014;20(Suppl. 2):1–26; Poutanen SM, Simor AE. CMAJ 2004;171:51–8

CDAD Disease ranges from asymptomatic carriage through diarrhoea to pseudomembranous colitis and death Estimated incidence is 38–95 cases per 100,000 patient days and 3.4–8.4 cases per 1000 admissions Case mortality is 1–2.5% Carriage is 1–3% in healthy adults Acquisition rate estimated at 13% for hospital stays of <2 weeks and 50% if >4 weeks Individuals sharing a room with a C. difficile-positive patient acquire the organism after a stay of 3.2 days, compared with 18.9 days for other individuals Schroeder MS. Am Fam Physician 2005;71:921–8

What would you prescribe now? Continue IV flucloxacillin and add oral metronidazole Continue IV flucloxacillin and add oral vancomycin Continue IV flucloxacillin and add oral fidaxomicin Stop IV flucloxacillin and add oral metronidazole Stop IV flucloxacillin and add oral vancomycin Stop IV flucloxacillin and add oral fidaxomicin Other

What other measures should be considered? Select appropriate antibiotic treatment Stop precipitating antibiotic if possible Stop any gastric acid suppressive therapy Supportive care (e.g. fluid balance, etc.) Infection control source precautions Infection control environmental precautions Some of the above All of the above None of the above

Contact precautions From Muto, CA. Poor outcomes associated with Clostridium difficile (CD)-associated diarrhea: Identification and control (slides with transcript) [PowerPoint]; 2007. Available from http://www.medscape.org/viewarticle/558476. Accessed 19 March, 2015. Used with permission from RMEI, LLC, and Postgraduate Institute for Medicine

Follow-up Flucloxacillin was continued Oral metronidazole 250 mg 8-hourly added Hip aspirate reported as having low numbers of WBCs and no growth Blood cultures were negative C. difficile reported as metronidazole-sensitive Patient continued to be pyrexial with profuse watery diarrhoea Sigmoidoscopy showed no evidence of pseudomembranous colitis

Treatment and outcome After 5 days, during which there was no improvement, flucloxacillin and metronidazole were stopped Oral vancomycin 500 mg 6-hourly was started The patient made a slow improvement Discharged home in 10 days No recurrence of hip sepsis

Readmission Readmitted after 10 days with 2-day history of increasingly severe diarrhoea Faeces test found to be positive for CDAD Laboratory tests showed dehydration with albumin 15 g/L (normal range 35–50 g/L) and WBC count 18.7 x 109/L (normal range 4.5–11.0 x 109/L)

What would you prescribe for recurrent CDAD? Standard oral metronidazole dose and duration Standard oral vancomycin dose and duration High-dose oral vancomycin (2 g/day) for standard duration Tapered oral vancomycin doses over 21 days Pulsed (3-day) standard oral vancomycin dose over 27 days Fidaxomicin Probiotics Probiotics and one of the above Other

Treatment and outcome Treated with general supportive care Started fidaxomicin 200 mg bid for 10 days Admitted into isolation and contact precautions started Response was slow initially, with reduction in stool frequency Good improvement by day 7 and discharged home to continue therapy There were no further relapses

Key learning points Always take an antibiotic history If there is a recent history of antibiotics and the patient has loose bowel motions, always consider CDAD If CDAD is present, stop the other antibiotics as soon as possible Perform risk assessment of CDAD cases and select therapy accordingly Always remember infection control measures

AIM core principles Patient outcomes Antibiotic choice Resistance Select the most appropriate antibiotic depending on the patient, risk factors, suspected infection and resistance Antibiotic choice If appropriate, change antibiotic dosage or therapy based on resistance and pathogen information Resistance Recognise that prior antimicrobial administration is a risk factor for the presence of resistant pathogens Infection control Wash hands adequately and wear gloves appropriately

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