Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization?

BACKGROUND: Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients. METHODS: Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups. RESULTS: Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics. CONCLUSIONS: Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

Easily modified factors contribute to delays in diagnosis of Clostridium difficile infection: a cohort study and intervention.

Although rapid laboratory tests are available for diagnosis of Clostridium difficile infection (CDI), delays in completion of CDI testing are common in clinical practice. We conducted a cohort study of 242 inpatients tested for CDI to determine the timing of different steps involved in diagnostic testing and to identify modifiable factors contributing to delays in diagnosis. The average time from test order to test result was 1.8 days (range, 0.2 to 10.6), with time from order to stool collection accounting for most of the delay (mean, 1.0 day; range, 0 to 10). Several modifiable factors contributed to delays, including not providing stool collection supplies to patients in a timely fashion, rejection of specimens due to incorrect labeling or leaking from the container, and holding samples in the laboratory for batch processing. Delays in testing contributed to delays in initiation of treatment for patients diagnosed with CDI and to frequent prescription of empirical CDI therapy for patients with mild to moderate symptoms whose testing was ultimately negative. An intervention that addressed several easily modified factors contributing to delays resulted in a significant decrease in the time required to complete CDI testing. These findings suggest that health care facilities may benefit from a review of their processes for CDI testing to identify and address modifiable factors that contribute to delays in diagnosis and treatment of CDI.

Utility of perirectal swab specimens for diagnosis of Clostridium difficile infection.

For 139 patients tested for Clostridium difficile infection by polymerase chain reaction, the sensitivity, specificity, positive predictive value, and negative predictive value of testing perirectal swabs vs stool specimens were 95.7%, 100%, 100%, and 99.1%, respectively. For selected patients, perirectal swabs provide an accurate toxigenic C. difficile detection strategy.

Clinical and infection control implications of Clostridium difficile infection with negative enzyme immunoassay for toxin.

In a prospective study of 132 patients with a diagnosis of Clostridium difficile infection (CDI) by polymerase chain reaction, 43 (32%) had enzyme immunoassay (EIA) results negative for toxin. EIA-negative patients with CDI did not differ in clinical presentation from EIA-positive patients and presented a similar risk for transmission of spores.

Acquisition of Clostridium difficile Colonization and Infection After Transfer From a Veterans Affairs Hospital to an Affiliated Long-Term Care Facility.

BACKGROUND Clostridium difficile infection (CDI) and asymptomatic carriage of toxigenic C. difficile are common in long-term care facilities (LTCFs). However, whether C. difficile is frequently acquired in the LTCF versus during acute-care admissions remains unknown. OBJECTIVE To test the hypothesis that LTCF residents often acquire C. difficile colonization and infection in the LTCF DESIGN This 5-month cohort study was conducted to determine the incidence of acquisition of C. difficile colonization and infection in asymptomatic patients transferred from a Veterans Affairs hospital to an affiliated LTCF. METHODS Rectal swabs were cultured for toxigenic C. difficile at the time of transfer to the LTCF and weekly for up to 6 weeks. We calculated the proportion of LTCF-onset CDI cases within 1 month of transfer that occurred in residents colonized on admission versus those with new acquisition in the LTCF. RESULTS Of 110 patients transferred to the LTCF, 12 (11%) were asymptomatically colonized with toxigenic C. difficile upon admission, and 4 of these 12 patients (33%) developed CDI within 1 month, including 3 recurrent and 1 initial CDI episode. Of 82 patients with negative cultures on transfer and at least 1 follow-up culture, 22 (27%) acquired toxigenic C. difficile colonization, and 4 developed CDI within 1 month, including 1 recurrent and 3 initial CDI episodes. CONCLUSION LTCF residents frequently acquired colonization with toxigenic C. difficile after transfer from the hospital, and 3 of 4 initial CDI cases with onset within 1 month of transfer occurred in residents who acquired colonization in the LTCF. Infect Control Hosp Epidemiol 2017;38:1070-1076.

Novel strategies for enhanced removal of persistent Bacillus anthracis surrogates and Clostridium difficile spores from skin.

BACKGROUND: Removing spores of Clostridium difficile and Bacillus anthracis from skin is challenging because they are resistant to commonly used antimicrobials and soap and water washing provides only modest efficacy. We hypothesized that hygiene interventions incorporating a sporicidal electrochemically generated hypochlorous acid solution (Vashe(®)) would reduce the burden of spores on skin. METHODS: Hands of volunteers were inoculated with non-toxigenic C. difficile spores or B. anthracis spore surrogates to assess the effectiveness of Vashe solution for reducing spores on skin. Reduction in spores was compared for Vashe hygiene interventions versus soap and water (control). To determine the effectiveness of Vashe solution for removal of C. difficile spores from the skin of patients with C. difficile infection (CDI), reductions in levels of spores on skin were compared for soap and water versus Vashe bed baths. RESULTS: Spore removal from hands was enhanced with Vashe soak (>2.5 log10 reduction) versus soap and water wash or soak (~2.0 log10 reduction; P<0.05) and Vashe wipes versus alcohol wipes (P<0.01). A combined approach of soap and water wash followed by soaking in Vashe removed >3.5 log10 spores from hands (P<0.01 compared to washing or soaking alone). Bed baths using soap and water (N =26 patients) did not reduce the percentage of positive skin cultures for CDI patients (64% before versus 57% after bathing; P =0.5), whereas bathing with Vashe solution (N =21 patients) significantly reduced skin contamination (54% before versus 8% after bathing; P =0.0001). Vashe was well-tolerated with no evidence of adverse effects on skin. CONCLUSIONS: Vashe was safe and effective for reducing the burden of B. anthracis surrogates and C. difficile spores on hands. Bed baths with Vashe were effective for reducing C. difficile on skin. These findings suggest a novel strategy to reduce the burden of spores on skin.

A Clostridium difficile infection (CDI) stewardship initiative improves adherence to practice guidelines for management of CDI.

A Clostridium difficile infection (CDI) stewardship initiative reduced inappropriate prescription of empirical CDI therapy and improved timeliness of treatment and adherence to clinical practice guidelines for management of CDI. The initiative required minimal resources and could easily be incorporated into traditional antimicrobial stewardship programs.

Potential for transmission of spores by patients awaiting laboratory testing to confirm suspected Clostridium difficile infection.

In a prospective study of inpatients tested for Clostridium difficile infection (CDI), skin and environmental contamination were common at the time of the order for CDI testing, and there were often delays in completion of testing. Preemptive isolation of patients with suspected CDI may reduce the risk of transmission.

Beyond the Hawthorne effect: reduction of Clostridium difficile environmental contamination through active intervention to improve cleaning practices.

Education and passive observation resulted in a significant improvement in housekeeper disinfection of nontoxigenic Clostridium difficile spores artificially inoculated onto surfaces in C. difficile infection rooms. A further significant reduction occurred with direct supervision and real-time feedback, suggesting that optimal disinfection is achieved by working closely with housekeepers.

Specialty care delivery: bringing infectious disease expertise to the residents of a Veterans Affairs long-term care facility.

OBJECTIVE: To initiate a long-term care facility (LTCF) infectious disease (LID) service that provides on-site consultations to LTCF residents to improve the care of residents with possible infections. DESIGN: Clinical demonstration project. SETTING: A 160-bed LTCF affiliated with a tertiary care Veterans Affairs (VA) hospital. PARTICIPANTS: Residents referred to the LID team. MEASUREMENTS: The reason for and source of LTCF residents' referral to the LID team and their demographic characteristics, infectious disease diagnoses, interventions, and hospitalizations were determined. RESULTS: Between July 2009 and December 2010, the LID consultation service provided 291 consultations for 250 LTCF residents. Referrals came from LTCF staff (75%) or the VA hospital's ID consult service (25%). The most common diagnoses were Clostridium difficile infection (14%), asymptomatic bacteriuria (10%), and urinary tract infection (10%). More than half of referred residents were receiving antibiotic therapy when they first saw the LID team; 46% of residents required an intervention. The most common interventions, stopping (32%) or starting (26%) antibiotics, were made in accordance with principles of antibiotic stewardship. CONCLUSION: The LID team represents a novel and effective means to bring subspecialty care to LTCF residents.

Appropriateness of empiric therapy in patients with suspected Clostridium difficile infection.

OBJECTIVE: The objective of this study was to test the hypothesis that many patients with suspected Clostridium difficile infection (CDI) receive inappropriate empiric therapy and/or receive continued therapy despite negative test results. METHODS: We performed a 3 month prospective cohort study at the Cleveland Veteran Affairs Medical Center to assess the appropriateness of empiric CDI therapy for all patients with stool samples submitted for CDI testing. Empiric therapy for CDI was considered appropriate if patients with suspected CDI had findings suggestive of severe or complicated illness. RESULTS: Of 251 patients tested for CDI, 53 (21%) received empiric treatment, including 45 (85%) treated with metronidazole and 8 (15%) treated with vancomycin. Of the 53 empirical therapy regimens, only 20 (38%) were deemed appropriate based on criteria for severe or severe, complicated CDI and 39 (74%) had negative laboratory testing for CDI. Twenty-one of 39 (54%) patients with negative testing were continued on therapy for three or more days despite the negative results. The key limitations of the study are the fact that it was conducted in a single institution and had a small sample size. CONCLUSION: In our facility, empiric treatment for CDI was common and more than half of empirical treatment was deemed inappropriate because patients did not meet criteria for severe CDI. Because CDI therapy may be associated with adverse effects, there is a need for interventions to improve the appropriateness of empiric CDI treatment.

Defining the vulnerable period for re-establishment of Clostridium difficile colonization after treatment of C. difficile infection with oral vancomycin or metronidazole.

BACKGROUND: Clostridium difficile is an anaerobic, spore-forming bacterium that is the most common cause of healthcare-associated diarrhea in developed countries. A significant proportion of patients receiving oral vancomycin or metronidazole for treatment of Clostridium difficile infection (CDI) develop recurrences. However, the period of vulnerability to re-establishment of colonization by C. difficile after therapy is not well defined. PRINCIPAL FINDINGS: In a prospective study of CDI patients, we demonstrated that most vancomycin-treated patients maintained inhibitory concentrations of vancomycin in stool for 4 to 5 days after therapy, whereas metronidazole was only detectable during therapy. From the time of elimination of the antibiotics to 14 to 21 days after therapy, a majority of stool suspensions supported growth of C. difficile and deep 16S rRNA sequencing demonstrated persistent marked alteration of the indigenous microbiota. By 21 to 28 days after completion of CDI treatment, a majority of stool suspensions inhibited growth of C. difficile and there was evidence of some recovery of the microbiota. CONCLUSIONS: These data demonstrate that there is a vulnerable period for re-establishment of C. difficile colonization after CDI treatment that begins within a few days after discontinuation of treatment and extends for about 3 weeks in most patients.

Outpatient healthcare settings and transmission of Clostridium difficile.

BACKGROUND: Recent reports suggest that community-associated Clostridium difficile infection (CDI) (i.e., no healthcare facility admission within 90 days) may be increasing in frequency. We hypothesized that outpatient clinics could be an important source for acquisition of community-associated CDI. METHODS: We performed a 6-month prospective study of CDI patients to determine frequency of and risk factors for skin and environmental shedding during outpatient visits and to derive a prediction rule for positive cultures. We performed a point-prevalence culture survey to assess the frequency of C. difficile contamination in outpatient settings and evaluated the frequency of prior outpatient visits in patients with community-associated CDI. RESULTS: Of 67 CDI patients studied, 54 (81%) had 1 or more outpatient visits within 12 weeks after diagnosis. Of 44 patients cultured during outpatient visits, 14 (32%) had skin contamination and 12 (27%) contaminated environmental surfaces. Decreased mobility, fecal incontinence, and treatment with non-CDI antibiotics were associated with positive cultures, whereas vancomycin taper therapy was protective. In patients not on CDI therapy, a prediction rule including incontinence or decreased mobility was 90% sensitive and 79% specific for detection of spore shedding. Of 84 clinic and emergency department rooms cultured, 12 (14%) had 1 or more contaminated environmental sites. For 33 community-associated CDI cases, 31 (94%) had an outpatient visit during the 12 weeks prior to onset of diarrhea. CONCLUSIONS: Patients with recent CDI present a significant risk for transmission of spores during outpatient visits. The outpatient setting may be an underappreciated source of community-associated CDI cases.

Daily disinfection of high-touch surfaces in isolation rooms to reduce contamination of healthcare workers' hands.

In a randomized nonblinded trial, we demonstrated that daily disinfection of high-touch surfaces in rooms of patients with Clostridium difficile infection and methicillin-resistant Staphylococcus aureus colonization reduced acquisition of the pathogens on hands after contacting high-touch surfaces and reduced contamination of hands of healthcare workers caring for the patients.

Acquisition of spores on gloved hands after contact with the skin of patients with Clostridium difficile infection and with environmental surfaces in their rooms.

In a prospective study of 30 patients with Clostridium difficile infection, we found that acquisition of spores on gloved hands was as likely after contact with commonly touched environmental surfaces (ie, bed rail, bedside table, telephone, call button) as after contact with commonly examined skin sites (ie, chest, abdomen, arm, hand).

Effective antimicrobial stewardship in a long-term care facility through an infectious disease consultation service: keeping a LID on antibiotic use.

DESIGN: We introduced a long-term care facility (LTCF) infectious disease (ID) consultation service (LID service) that provides on-site consultations to residents of a Veterans Affairs (VA) LTCF. We determined the impact of the LID service on antimicrobial use and Clostridium difficile infections at the LTCF. SETTING: A 160-bed VA LTCF. METHODS: Systemic antimicrobial use and positive C. difficile tests at the LTCF were compared for the 36 months before and the 18 months after the initiation of the ID consultation service through segmented regression analysis of an interrupted time series. RESULTS: Relative to that in the preintervention period, total systemic antibiotic administration decreased by 30% (P<.001), with significant reductions in both oral (32%; P<.001) and intravenous (25%; P=.008) agents. The greatest reductions were seen for tetracyclines (64%; P<.001), clindamycin (61%; P<.001), sulfamethoxazole/trimethoprim (38%; P<.001), fluoroquinolones (38%; P<.001), and ß-lactam/ß-lactamase inhibitor combinations (28%; P<.001). The rate of positive C. difficile tests at the LTCF declined in the postintervention period relative to preintervention rates (P=.04). CONCLUSIONS: Implementation of an LTCF ID service led to a significant reduction in total antimicrobial use. Bringing providers with ID expertise to the LTCF represents a new and effective means to achieve antimicrobial stewardship.

Clostridium difficile infection in a Department of Veterans Affairs long-term care facility.

In a Veterans Affairs medical center, 39% of healthcare facility-onset, healthcare facility-associated Clostridium difficile infections had their onset in the affiliated long-term care facility (LTCF). Eighty-five percent of LTCF-onset patients had been transferred from the hospital within the past month. Delays in diagnosis and treatment were common for LTCF-onset patients.

Effectiveness of routine patient bathing to decrease the burden of spores on the skin of patients with Clostridium difficile infection.

For 74 patients with Clostridium difficile infection, the quality and frequency of bathing was often limited because of such factors as the presence of devices, decreased mobility, and pain. Routine bathing practices had limited efficacy in decreasing the burden of spores on skin; however, showers were more effective than bed baths.

Evaluation of an alcohol-based power sanitizing system for decontamination of hospital rooms of patients with methicillin-resistant Staphylococcus aureus carriage.

A power sanitizing system that delivers a sanitizing mist of alcohol, rendered nonflammable by a carbon dioxide carrier, and a low concentration of quaternary ammonium compound, was easy to use, provided thorough coverage of surfaces, and significantly reduced vancomycin-resistant Enterococcus and methicillin-resistant Staphylococcus aureus contamination on commonly touched hospital surfaces. However, it was not as consistently effective for elimination of pathogens as 10% bleach solution.