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Three Part Question

In [adult patients presenting with undifferentiated travellers’ diarrhoea] does the use of [quinolone antibiotics in combination with loperamide compared to antibiotics alone] [reduce duration of symptoms]?

Clinical Scenario

A 20-year-old male student attends the Emergency Department complaining of 2 days symptoms of diarrhoea having returned to the UK yesterday after a 3 week backpacking visit to Turkey. He describes no discriminatory features aside from isolated diarrhoea and occasional crampy abdominal pains, with no dysentery (mucus/bloody stools). His examination is unremarkable aside from mild lower abdominal tenderness. He is well hydrated. He has taken a single dose of ciprofloxacin provided by a friend, but requests further treatment to stop diarrhoea. You consider the addition of loperamide.

Search Strategy

EMBASE search using the operators (quinolone* OR fluoroquinolone* OR fluroquinolone*) AND loperamide AND (travel* AND diar*). No limits on date/language/age.

MEDLINE search (all fields) using the operators (quinolone* OR fluoroquinolone* OR fluroquinolone*) AND loperamide AND (travel* AND diar*). No limits on date/language/age.

Cochrane search (diar* AND loperamide AND quinolone* OR fluoroquinolone*) and for individual operators separately (diar*, loperamide, quinolone*, fluoroquinolone*).

References in papers manually checked for relevant papers.

Search Outcome

Embase search revealed 52 studies of which 2 were relevant to the question.
Medline search revealed 21 studies, 1 of which was relevant to the question, but not unique (same relevant paper as in Embase search).
Cochrane combined search revealed 3 clinical trial results, 1 relevant to the question, not unique to the above search results. Cochrane individual operator searches revealed 139 studies, non relevant to the question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Ericsson et al. 1997 US	166 adults (US students recently arrived to Mexico), acute diarrhoea, less than 2 weeks duration.	Randomised assessor-blind study. 3 treatment groups compared: A) 1 dose ofloxacin 400mg B) BD dose ofloxacin 200mg for 5 days C) 1 dose ofloxacin 400mg plus initial loperamide 4mg	Intention to treat analysis		Not double-blinded. Researchers question 200mg dosage level (perhaps too low)
			Hours of repeated diarrhoeal episodes	A) 14 B) 28 C) 0; p<0.0001
			Shigella later isolated	No benefit of loperamide and ofloxacin
Petrucelli et al. 1992 USA	1432 US military personnel in temporary posting to Thailand	Randomised double-blind placebo controlled trial. Treatment groups A)single dose 750mg ciprofloxacin with placebo; B) single dose 750mg ciprofloxacin with loperamide; C) 3 day course of 500mg ciprofloxacin BD with loperamide. Loperamide regimen - 4mg initially, with 2mg after each loose bowel motion.	Last unformed stool (hrs)	A)36+/-3.4 B) 34+/-4.8 C) 44+/-6.5. No significance	Dosages not overseen - missed doses in treatment and placebo groups (n=14). 1 or more missed doses in A) n=2, B) n=3, C) n=2. Authors acknowledge study probably underpowered to detect group differences in stratified analyses. Subjects also taking doxycycline malaria prophylaxis as confounding factor.
			Last liquid stool (hrs)	Not reported
			Complete recovery (all symptoms; hrs)	A) 38+/-3.1 B) 40+/-4.7 C) 45+/-6.2. No significance.
			Cumulative no. loose bowel motions	A) 3.9+/-0.5 B) 3.1+/-0.6 C) 2.0+/-0.3*. *Significant at p=0.01.

Comment(s)

Quinolones and loperamide may reduce duration of symptoms, except in cases where Shigella later confirmed as organism (Ericsson et al.). Fewer loose motions are to be expected with combination loperamide and quinolone therapy.

Clinical Bottom Line

In travellers' diarrhoea the empirical use of quinolones in addition to loperamide reduces duration and severity of symptoms. If treatment can be delayed to obtain culture results (therefore a tailored antimicrobial regimen) this is clearly preferential.

References

1. Ericsson, C. D., DuPont, H. L., Mathewson, J. J. Single Dose Ofloxacin plus Loperamide Compared with Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea Journal of Travel Medicine 1997; 4:3-7
2. Petrucelli, B. P., Murphy, G. S., Sanchez, J. L, Walz, S., DeFraites, J. G., Haberberger, R. L., Echeverria, P., Taylor, D. N. Treatment of Traveler's diarrhea with Ciprofloxacin and Loperamide Journal of Infectious Diseases 1992; 165:557-60