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Importance: Clostridium difficile is the most common cause of health care-associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients., Objective: To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C. difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C. difficile infection (CDI)., Design, Setting, and Participants: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe., Interventions: Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 10(4) spores/d for 7 days (n = 43), 10(7) spores/d for 7 days (n = 44), or 10(7) spores/d for 14 days (n = 42), or placebo for 14 days (n = 44)., Main Outcomes and Measures: The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6., Results: Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7) spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P < .001)., Conclusions and Relevance: Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence., Trial Registration: clinicaltrials.gov Identifier: NCT01259726.

Importance: Daily bathing of critically ill patients with the broad-spectrum, topical antimicrobial agent chlorhexidine is widely performed and may reduce health care-associated infections., Objective: To determine if daily bathing of critically ill patients with chlorhexidine decreases the incidence of health care-associated infections., Design, Setting, and Participants: A pragmatic cluster randomized, crossover study of 9340 patients admitted to 5 adult intensive care units of a tertiary medical center in Nashville, Tennessee, from July 2012 through July 2013., Interventions: Units performed once-daily bathing of all patients with disposable cloths impregnated with 2% chlorhexidine or nonantimicrobial cloths as a control. Bathing treatments were performed for a 10-week period followed by a 2-week washout period during which patients were bathed with nonantimicrobial disposable cloths, before crossover to the alternate bathing treatment for 10 weeks. Each unit crossed over between bathing assignments 3 times during the study., Main Outcomes and Measures: The primary prespecified outcome was a composite of central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonia (VAP), and Clostridium difficile infections. Secondary outcomes included rates of clinical cultures that tested positive for multidrug-resistant organisms, blood culture contamination, health care-associated bloodstream infections, and rates of the primary outcome by ICU., Results: During the chlorhexidine bathing period, 55 infections occurred: 4 CLABSI, 21 CAUTI, 17 VAP, and 13 C difficile. During the control bathing period, 60 infections occurred: 4 CLABSI, 32 CAUTI, 8 VAP, and 16 C difficile. The primary outcome rate was 2.86 per 1000 patient-days during the chlorhexidine and 2.90 per 1000 patient-days during the control bathing periods (rate difference, -0.04; 95% CI, -1.10 to 1.01; P = .95). After adjusting for baseline variables, no difference between groups in the rate of the primary outcome was detected. Chlorhexidine bathing did not change rates of infection-related secondary outcomes including hospital-acquired bloodstream infections, blood culture contamination, or clinical cultures yielding multidrug-resistant organisms. In a prespecified subgroup analysis, no difference in the primary outcome was detected in any individual intensive care unit., Conclusion and Relevance: In this pragmatic trial, daily bathing with chlorhexidine did not reduce the incidence of health care-associated infections including CLABSIs, CAUTIs, VAP, or C difficile. These findings do not support daily bathing of critically ill patients with chlorhexidine., Trial Registration: clinicaltrials.gov Identifier: NCT02033187.

Clostridium difficile infection (CDI) is a common and increasingly severe nosocomial infectious disease. The case of Mr S, a 76-year-old man with multiple recurrences of CDI, illustrates the difficulties in treating recurrent disease and the way it complicates the management of other medical conditions. Risk factors for CDI include antimicrobial use, hospital admission, advancing age, and severe underlying disease. A clinical diagnosis of CDI is usually confirmed by identifying C. difficile toxins in a stool sample. Evidence supports metronidazole, 500 mg every 6 hours for 10 to 14 days, as the treatment of choice for mild to moderately severe CDI. Oral vancomycin, 125 mg every 6 hours for 10 to 14 days, is recommended for severe CDI, for which it is more effective than metronidazole. Recurrent CDI occurs in more than 20% of patients when metronidazole or vancomycin treatment is discontinued. Few studies have evaluated treatment options for recurrent CDI, but a prolonged, tapering, and pulse-dosed regimen of oral vancomycin is commonly used. Careful attention to antimicrobial stewardship and infection control practices is essential to curb this nosocomial, iatrogenic disease.

A clustering of Clostridium difficile-associated disease in a department of surgery prompted a program of infection control and the evaluation of contributing factors. Fifty patients had diarrhea and positive assays for C difficile cytotoxin during the study period. Twenty-one of the 36 cases that developed among patients admitted to the surgical services occurred on two adjacent general surgery wards that shared attending surgeons and house staff. Perioperative prophylactic antibiotics predated C difficile-associated disease in 20 patients, 12 of whom had short courses (less than 24 hours). Symptoms were typically nonspecific and early diagnosis may be difficult. Incidence remained high, despite infection control measures, until the coincidental closure of two surgical wards. Clostridium difficile-associated disease is a nosocomial infection that can be associated with short courses of prophylactic antibiotics. Recommendations regarding the use of perioperative prophylaxis should recognize C difficile-associated disease as a significant potential complication.

The value of prophylactic oral gentamicin sulfate therapy in the prevention of necrotizing enterocolitis (NEC) was evaluated in a group of 42 high-risk neonates over a four-month period in a randomized, double-blind controlled trial. Twenty babies in the treatment group received 2.5 mg/kg of gentamicin sulfate every six hours for one week after birth, and 22 babies received dextrose-and-water placebo in an equivalently small volume. None of the 20 gentamicin-treated babies developed NEC. Four of the control babies did. Two of these babies died, and their diagnosis was pathologically confirmed. This difference in the incidence of NEC between the treatment and control group was significant at the .05 level. These results support the prophylactic use of orally given gentamicin for selected babies at high risk for NEC, particularly those born prematurely and those who have a history of perinatal asphyxia or umbilical artery catheterization or both. Continued surveillance for changes in antimicrobial sensitivity patterns is recommended.

Necrotizing enterocolitis of newborn infants virtually vanished from our nurseries during the four years since the introduction of a slowly progressive feeding regimen. This cautions approach to feeding has been applied to selected infants whose condition during labor and delivery or whose neonatal problems indicate that they are at risk.

To test the hypothesis that delayed oral feedings would lower the incidence of necrotizing enterocolitis (NEC) in neonates weighing less than 1,500 g at birth, we compared the incidence of NEC in two matched groups of newborns. High-risk neonates were selected from 160 consecutive admissions, based on a cumulative risk scoring of their illness during the first three days of life. One group (N = 20) was given no oral feedings for two weeks, receiving nutrition parenterally, while the other (N = 18) was given incremental enteric feedings of dilute infant formula or breast milk during the first two weeks of life. The overall incidence of NEC in the parenterally fed group was 60% (12/20) compared with 22% (4/18) in the early-oral-feeding group. These data show that withholding oral feedings for two weeks postnatally does not lower the incidence of NEC and in fact may promote its occurrence.