Diarrhea: Treatment ==================== þ Community-Acquired C. Difficile - Flagyl 500 mg PO tid or 250 mg PO qid for 10-14 d 500 mg IV qid for 10-14 d - Vancomycin 125 mg PO qid for 10-14 d; 40 mg/kg/d PO divided tid/qid for 7-10 d; not to exceed 2 g/d Zinc: - reduces diarrhea in kids [Lukacik, M., R. L. Thomas, et al. (2008). "A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea." Pediatrics 121(2): 326-36.] OBJECTIVE: Children in developing countries are at a high risk for zinc deficiency. Supplemental zinc has previously been shown to provide therapeutic benefits in diarrhea. The objective of this study was to examine the efficacy and safety of supplemental oral zinc therapy during recovery from acute or persistent diarrhea. METHODS: We conducted a meta-analysis of randomized, controlled trials to compare the efficacy and safety of supplementary oral zinc with placebo in children with acute and persistent diarrhea. Results were reported using a pooled relative risk or a weighted mean difference. A total of 22 studies were identified for inclusion: 16 examined acute diarrhea (n = 15,231), and 6 examined persistent diarrhea (n = 2968). RESULTS: Mean duration of acute diarrhea and persistent diarrhea was significantly lower for zinc compared with placebo. Presence of diarrhea between zinc and placebo at day 1 was not significantly different in acute diarrhea or persistent diarrhea trials. At day 3, presence was significantly lower for zinc in persistent diarrhea trials (n = 221) but not in acute diarrhea trials. Vomiting after therapy was significantly higher for zinc in 11 acute diarrhea trials (n = 4438) and 4 persistent diarrhea trials (n = 2969). Those who received zinc gluconate in comparison with zinc sulfate/acetate vomited more frequently. Overall, children who received zinc reported an 18.8% and 12.5% reduction in average stool frequency, 15.0% and 15.5% shortening of diarrhea duration, and a 17.9% and 18.0% probability of reducing diarrhea over placebo in acute and persistent trials, respectively. CONCLUSIONS: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea; however, the mechanisms by which zinc exerts its antidiarrheal effect have not been fully elucidated. ] General ------- þ Bacteria for Diarrhea - Lactinex: "dietary supplement" that contains Lactobacillius acidophilus and L. bulgaricus, similar to eating youghurt with active cultures, available as chewable tablets or granules. Reportedly, a study by Tankanow et al, doubl-blind placebo-controlled trial of 38 kids 5 mo-6 years, taking amoxicillin for 10 days: 2/3 of both groups got diarrhea, but Lactinex group's diarrhea slowed earlier. - Florastor: "dietary supplement" contains SAccharomyces boulardi, acts like normal gut flora, resistant to most antibiotics, and has enzymes that proteolyze C. difficile toxins A and B ad inhibits their binding to receptors. In a placebo-controlled double blind trial, it reduced antibiotic-associated diarrhea by more than 50%. þ Standard is to start treatment empirically, even for non-traveler's diarrhea. - for watery diarrhea, no other symptoms: Pepto-Bismol, Imodium - Travelers' Diarrhea: standard treatment is with Bactrim or quinolone (Cipro, Floxin, or Noroxin) or possibly Doxycycline + Imodium - non-traveler's diarrhea: mostly self-limited, but if bad, may treat with quinolones - "Fluorquinolones Are First-Choice Therapy for Salmonellosis" (headline from Scientific American Medicine Bulletin, December 1995. (ceftriaxone is an alternative) þ Antimotility Agents - Antimotility agents such as Lomitil and Imodium thought to make invasive diarrhea worse, but Army (DuPont's Mexican study) showed it to be safe if taken with Bactrim, Doxycycline, or Cipro. - Army medical research: 8 oz bottle of Imodium will bring relief of travelers' diarrhea in 4 hours. - If signs of dysentery, only use Imodium if starting empiric antibiotics. þ Antibiotics - More resistance to Bactrim and doxycycline, so better to use Noroxin and Cipro. Only thing they don't treat is C. difficile. But, can't be used in kids or pregnant women. New: Floxin (ofloxacin): similar to Cipro and Noroxin, but less interaction with theophylline and caffeine. - New concept for Travelers' Diarrhea: take 2 Imodium and a single 750mg Cipro early. As effective as 3 days of "normal" dose of Cipro. [Taylor DN, et al. Treatment of traveler's diarrhea with antimotility drugs and antibiotics. Abstract 130, American Society of Tropical Medicine and Hygiene Annual Meeting, New Orleans, Nov. 1990] [Petruccelli BP; Murphy GS; Sanchez JL; Walz S; and others. Treatment of traveler's diarrhea with ciprofloxacin and loperamide. Division of Preventive Medicine, Walter Reed Army Institute of Research, Washington, DC. J Infect Dis 1992 Mar;165(3):557-60 Unique Identifier: MEDLINE 92166440. To determine the efficacy of loperamide given with long- and short-course quinolone therapy for treating traveler's diarrhea, 142 US military personnel were randomized to receive a single 750-mg dose of ciprofloxacin with placebo, 750 mg of ciprofloxacin with loperamide, or a 3-day course of 500 mg of ciprofloxacin twice daily with loperamide. Culture of pretreatment stool specimens revealed campylobacters (41%), salmonellae (18%), enterotoxigenic Escherichia coli (ETEC, 6%), and shigellae (4%). Of the participants, 87% completely recovered within 72 h of entry. Total duration of illness did not differ significantly among the three treatment groups, but patients in the 3-day ciprofloxacin plus loperamide group reported a lower cumulative number of liquid bowel movements at 48 and 72 h after enrollment compared with patients in the single-dose ciprofloxacin plus placebo group (1.8 vs. 3.6, P = .01; 2.0 vs. 3.9, P = .01). While not delivering a remarkable therapeutic advantage, loperamide appears to be safe for treatment of non-ETEC causes of traveler's diarrhea. Two of 54 patients with Campylobacter enteritis had a clinical relapse after treatment that was associated with development of ciprofloxacin resistance.] - David Shlim says optimum is somewhere between 1 and 6 pills, maybe just take until better. - Quinolones don't destroy the normal anaerobic gut flora [Reeves DS. The effect of quinolone antibacterials on the gastrointestinal flora compared with that of other antibacterials. J Antimicrob Cemother 1986; 16:(suppl D):89-102.] - Enterovioform (iodocholorhydroxyquin) and related halogenated hydroxyquinoline derivaties not recommended for prophylaxis: not only ineffective, but also may cause myelo-optic neuropathy; still available OTC in Latin America and Europe. [Wolfe MS. Acute diarrhea associated with travel. Am J Med 1990; 88 (6A):34S-37S.] - Bactrim not recommended for prophylaxis of Travelers' Diarrhea: incidence of Stevens-Johnson syndrome is one in a million. [Wolfe MS. Acute diarrhea associated with travel. Am J Med 1990; 88 (6A):34S-37S.] - One study suggests that there are many cases of Travelers' Diarrhea that won't culture out any organism but that will nonetheless get better with a quinolone. [Scott DA, Haberberger RL, Thornton SA. Norfloxacin for the prophylaxis of travelers' diarrhea in U.D. military personnel. Am J Trop Med Hyg 1990;42(2):160-164.] - people get better in 2 days with a quinolone; must be adult and nonpregnant. - For shigella: single dose Cipro as good as longer courses except Type 1 [119-120] - For children and infants > i month: furazolidone (Furoxone), available in tablets 100 mg, liquid 50mg/15cc. Will not deplete normal flora, but treats E. coli, Shigella, Salmonella, Vibrio, Staph, Giardia, Proteus, Aerobacter (per PDR). Has antabuse-like reaction, so avoid alcohol. May interfere with MAO inhibitors. Dosage: 100 mg QID. For children: i mo to i year: 2.5-5 cc QID i yr to 4 yrs: 5-7.5 cc QID > 5 years: 7.5-15 cc QID Sizes: 60 and 473 cc Per Dr. Geno Marton at the manufacturer, this reference also shows it has utility against Campylobacter and Yersinia. [Cerlson JR. Antimicrob Agents Chemother. 1983;24:509-513.] Flagyl: 250 TID for 7 days for Giardia, 750 TID for 10 days for amoebic diarrhea. Ann Intern Med 1993 Apr 15;118(8):582-586 Ciprofloxacin and loperamide in the treatment of bacillary dysentery. Murphy GS, Bodhidatta L, Echeverria P, Tansuphaswadikul S, Hoge CW, Imlarp S, Tamura K Naval Medical Research Unit Number 2, Jakarta, Indonesia. OBJECTIVE: To compare the safety and efficacy of loperamide plus ciprofloxacin with those of ciprofloxacin alone in the treatment of bacillary dysentery. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Hospital in Thailand. PARTICIPANTS: Eighty-eight adults with dysentery seeking medical care between November 1990 and February 1992. Patients who had received prior antibiotics or antimotility drugs were excluded. INTERVENTION: All 88 patients with dysentery were treated with ciprofloxacin, 500 mg twice daily for 3 days. Forty-two of these patients were randomly assigned to receive loperamide, a 4-mg initial dose followed by 2 mg after every loose stool (as many as eight caplets [16 mg] daily), and 46 were randomly assigned to receive placebo. MEASUREMENTS: Stools were collected daily until resolution of diarrhea and again after 10 days. The time to passage of the last unformed stool, number of unformed stools, and symptoms were recorded after treatment. RESULTS: Shigella or enteroinvasive Escherichia coli (53%), Vibrio parahaemolyticus (16%), and Salmonella (7%) were the most common bacterial enteric pathogens identified in 88 patients with dysentery. In patients infected with Shigella or enteroinvasive E. coli, the median duration of diarrhea was 19 hours (25th to 75th percentiles, 6 to 42 hours) for those receiving loperamide plus ciprofloxacin compared with 42 hours (21 to 46 hours) for those receiving ciprofloxacin alone (P = 0.028). The median number of diarrheal stools for those receiving ciprofloxacin and loperamide was 2.0 (1 to 5 stools) compared with 6.5 (2 to 9 stools) for those receiving ciprofloxacin alone (P = 0.016). None of the participants had a temperature greater than 38 degrees C after 24 hours of treatment. None of the patients was infected with the same bacterial enteric pathogen more than 1 day after receiving treatment. CONCLUSIONS: Loperamide decreases the number of unformed stools and shortens the duration of diarrhea in dysentery caused by Shigella in adults treated with ciprofloxacin. Ann Ann Intern Med 1991 May 1;114(9):731-734 Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial. Taylor DN, Sanchez JL, Candler W, Thornton S, McQueen C, Echeverria P Walter Reed Army Institute of Research, Washington, DC. OBJECTIVE: To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: United States Army hospital in Egypt. PARTICIPANTS: United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded. INTERVENTIONS: All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo. MEASUREMENTS: Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common. MAIN RESULTS: After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19). CONCLUSIONS: In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe JAMA 1990 Jan 12;263(2):257-261 Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide. Ericsson CD, DuPont HL, Mathewson JJ, West MS, Johnson PC, Bitsura JA Department of Medicine, University of Texas Medical School, Houston, TX 77030. In a randomized, double-blind, placebo-controlled trial, 227 US adults with acute diarrhea in Mexico received a single dose of sulfamethoxazole and trimethoprim (1600/320 mg) or 3 days of therapy with loperamide hydrochloride (4-mg loading dose, then 2 mg orally after each loose stool), sulfamethoxazole-trimethoprim (800/160 mg orally twice daily), or the combination of both. Subjects treated with the combination had the shortest average duration of diarrhea compared with the placebo group (1 hour vs 59 hours), took the least amount of loperamide after the loading dose (3.8 mg), and had the shortest duration of diarrhea associated with fecal leukocytes or blood-tinged stools (4.5 hours). A single dose of sulfamethoxazole-trimethoprim was also efficacious (28 vs 59 hours), but loperamide alone was significantly effective only when treatment failures were treated with antibiotics (33 vs 58 hours). The combination of sulfamethoxazole-trimethoprim plus loperamide can be highly recommended for the treatment of most patients with traveler's diarrhea.