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68-year-old male with a history of methicillin-sensitive Staphylococcus aureus joint infection presents with malaise, fevers, and gastrointestinal symptoms. Initial tests and treatment are discussed along with potential pathogens and antibiotic regimens. The patient's diagnosis is a relapse of the hip infection, and treatment includes IV flucloxacillin. However, the patient develops Clostridium difficile-associated diarrhea, requiring a change in antibiotic treatment and additional measures.
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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. • Shigellaspp. • 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. 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 • 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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