Use Of Oral Vancomycin Research Articles

Use of Oral Vancomycin for Clostridioides difficile Infection and the Risk of Vancomycin-Resistant Enterococci.

Vancomycin is now a preferred treatment for all cases of Clostridioides difficile infection (CDI), regardless of disease severity. Concerns remain that a large-scale shift to oral vancomycin may increase selection pressure for vancomycin-resistant Enterococci (VRE). We evaluated the risk of VRE following oral vancomycin or metronidazole treatment among patients with CDI. We conducted a retrospective cohort study of patients with CDI in the US Department of Veterans Affairs health system between 1 January 2006 and 31 December 2016. Patients were included if they were treated with metronidazole or oral vancomycin and had no history of VRE in the previous year. Missing data were handled by multiple imputation of 50 datasets. Patients treated with oral vancomycin were compared to those treated with metronidazole after balancing on patient characteristics using propensity score matching in each imputed dataset. Patients were followed for VRE isolated from a clinical culture within 3 months. Patients treated with oral vancomycin were no more likely to develop VRE within 3 months than metronidazole-treated patients (adjusted relative risk, 0.96; 95% confidence interval [CI], .77 to 1.20), equating to an absolute risk difference of -0.11% (95% CI, -.68% to .47%). Similar results were observed at 6 months. Our results suggest that oral vancomycin and metronidazole are equally likely to impact patients' risk of VRE. In the setting of stable CDI incidence, replacement of metronidazole with oral vancomycin is unlikely to be a significant driver of increased risk of VRE at the patient level.In this multicenter, retrospective cohort study of patients with Clostridioides difficile infection, the use of oral vancomycin did not increase the risk of vancomycin-resistant Enterococci infection at 3 or 6 months compared to metronidazole.

Retrospective evaluation of fidaxomicin versus oral vancomycin for treatment of Clostridium difficile infections in allogeneic stem cell transplant

Objective/backgroundClostridium difficile infection (CDI) is a potential complication during hematopoietic stem cell transplantation (HSCT), and no specific recommendations exist regarding treatment of CDI in allogeneic SCT patients. Use of metronidazole and oral vancomycin has been associated with clinical failure. Fidaxomicin has previously been found noninferior to the use of oral vancomycin for the treatment of CDI, and no studies have compared the use of oral vancomycin with fidaxomicin for the treatment of CDI in allogeneic SCT. MethodsThis retrospective chart review included 96 allogeneic SCT recipients who developed CDI within 100 days following transplantation. Participants were treated with oral vancomycin (n = 52) or fidaxomicin (n = 44). The primary outcome was clinical cure, defined as no need for further retreatment 2 days following completion of initial CDI treatment. Secondary outcomes were global cure, treatment failure, and recurrent disease. ResultsNo differences in clinical cure were observed between patients receiving oral vancomycin or fidaxomicin (75% vs. 75%, p = 1.00). Secondary outcomes were similar between oral vancomycin and fidaxomicin in regards to global cure (66% vs. 67%, p = .508), treatment failure (28% vs. 27%, p = .571), and recurrent disease (7% vs. 5%, p = .747). In a subanalysis of individuals that developed acute graft-versus-host disease following CDI, the difference in mean onset of acute graft-versus-host disease was 21.03 days in the oral vancomycin group versus 32.88 days in the fidaxomicin group (p = .0031). ConclusionThe findings of this study suggest that oral vancomycin and fidaxomicin are comparable options for CDI treatment in allogeneic SCT patients within 100 days following transplant.

Early prophylactic antibiotics for severe acute pancreatitis: A population-based cohort study using a nationwide database in Japan.

Previous studies evaluating the clinical benefits of prophylactic antibiotics for severe acute pancreatitis (SAP) have generated inconsistent results due to heterogeneities among the study settings. We determined if early prophylactic antibiotics improved the outcomes of SAP patients using a study designed to overcome these previous methodological weaknesses. We conducted a retrospective cohort study of SAP patients discharged between July 2010 and March 2016, using a Japanese nationwide inpatient database. We divided patients into those with early prophylactic carbapenem use (prophylaxis group) and those without prophylaxis (control group). The primary outcome was in-hospital mortality and the secondary outcomes included oral vancomycin use and others. We identified a total of 3354 eligible patients, including 2493 in the prophylaxis group and 861 in the control group. The overall in-hospital mortality was 12.8%. Prophylactic antibiotics were not significantly associated reduced in-hospital mortality according to Cox regression analysis (hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.62-1.23) or instrumental variable analysis (risk difference,-1.2%; 95% CI,-9.8%-7.4%). However, prophylactic antibiotic use was significantly associated with oral vancomycin use during hospitalization in a competing-risk model (subdistribution HR, 1.91; 95% CI, 1.02-3.56). The present study suggests that routine early prophylactic antibiotic use have no significant clinical benefit in SAP patients but may increase the risk of hospital-acquired infections.

Fecal Microbiota Transplant Decreases Mortality in Patients With Refractory Severe and Severe Complicated Clostridium difficile Infection Not Eligible for Colectomy: 2017 Fellows-in-Training Award (Colon Category)

Introduction: In patients with severe±complicated Clostridium difficile infection (CDI) non-responsive to medical therapy, mortality approaches 80% if colectomy is not offered as salvage therapy. We aimed to examine the effect of sequential fecal microbiota transplant(s) (FMT) with selective use of oral vancomycin on hospitalization-associated mortality rates in severe±complicated CDI patients not eligible to undergo surgery due to significant medical comorbidities. Methods: We conducted a retrospective cohort study by examining the EMR and FMT database between 2009-2016 at a tertiary referral center where an inpatient FMT program was implemented in 2013. FMT has been routinely offered to all qualifying patients since Jan of 2013. Inclusion criteria were: A) severe±complicated CDI per ACG guidelines, B) no response to vancomycin after ≥ 5 days of therapy C) not eligible for colectomy due to underlying medical status per surgical consultation. We compared baseline characteristics and rates of 30-day mortality between patients who received FMT(s) and those who did not. Adjusted effect of FMT was estimated using the penalized logistic regression using the Firth's approach. Results: 32 hospitalizations with severe±complicated CDI not eligible for colectomy by the surgical team were identified; 17 patients continued medical therapy and 15 were treated with sequential FMT protocol. Of those cured by FMT, an average of 1.83±0.7 FMTs were needed. Serum albumin and WBC were comparable between groups (Table 1). Regarding prognostically important variables, patients receiving FMT were significantly older (mean 75 vs 59 years, P< 0.001) and more commonly had toxic megacolon (40.0% vs 5.9%, P< 0.033), although rates of acute kidney injury (AKI) were slightly lower (73.3% vs 100%, P=0.038) compared to patients who did not receive FMT. Importantly, patients receiving sequential FMT instead of routine medical therapy had decreased CDI-related mortality (20.0% vs 82.4%, P=0.001) and all-cause mortality (20.0% vs 94.1%, P<0.001). These results remained the same after controlling for factors that significantly differed between those who received FMT and those who did not, including age, AKI, and toxic megacolon.Table: Table. Patient Characteristics and Outcomes for Patients Hospitalized with Refractory Severe and/or Complicated CDI too Ill to be Considered for ColectomyConclusion: An inpatient FMT protocol utilizing sequential FMT decreases mortality in high-risk patients compared to routine medical therapy in patients with severe±complicated CDI who are not eligible colectomy due to poor medical status.

Know When to Test: Optimizing Diagnostic Practices for Clostridium difficile Infection (CDI) Among Patients at a Tertiary-Care Cancer Center

BackgroundPolymerase chain reaction (PCR) based diagnostic testing for the detection of toxigenic Clostridium difficile infection (CDI) does not distinguish between carriers and patients with true CDI. As a result, CDI is over-diagnosed in hospitalized patients with diarrhea. Unnecessary testing generates false positives and several downstream sequelae.Aim: The aim of this study was to reduce unnecessary testing for CDI through an electronic alert, targeted education, and implementation of evidence-based laboratory testing policy.MethodsIn order to quickly identify laxative induced diarrhea and avoid CDI testing, an electronic alert was created in the electronic medical record (EMR) system. The alert was built on a logic that identified patients who had received laxatives within 48 hours of a CDI PCR test order. The alert additionally provided the rationale for avoiding testing in patients on laxatives and guidance on appropriate testing for CDI. The following steps were taken simultaneously to complement these efforts: 1) Infection Control conducted hospital-wide education for licensed independent practitioners on a CDI testing algorithm 2) Laboratory based policy was instated to reject all formed stools (Bristol Stool Chart types 1 through 4) for CDI testing.ResultsIn the 6 month pre-intervention period, there were 29 CDI tests per 1000 patient-days. In the post-intervention period, CDI tests decreased to 19 per 1000 patient-days, a 35% decrease (P < 0.0001). The decline in testing has been sustained for 7 months. The following observations were also made: 1) HAI rate reduction of 28%; 2) decrease in oral vancomycin use.ConclusionDecreasing inappropriate testing has several distinct advantages, including reducing excessive and unnecessary antibiotic use, avoiding misclassification of carriers as CDI cases, normalizing healthcare-associated CDI rates, and diminishing healthcare costs associated with preventable tests. Laboratories that use PCR only testing for CDI diagnosis should follow stringent policies to ensure that only patients with high pretest probability are tested. EMR systems are a useful and effective resource to achieve this for patients with laxative induced diarrhea.Disclosures All authors: No reported disclosures.

Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice.

The use of oral vancomycin or metronidazole for treatment of Clostridium difficile infection (CDI) may promote colonization by health care-associated pathogens due to disruption of the intestinal microbiota. Because the macrocyclic antibiotic fidaxomicin causes less alteration of the intestinal microbiota than vancomycin, we hypothesized that it would not lead to a loss of colonization resistance to vancomycin-resistant enterococci (VRE) and extended-spectrum-β-lactamase-producing Klebsiella pneumoniae (ESBL-Kp). Mice (8 per group) received orogastric saline, vancomycin, or fidaxomicin daily for 5 days at doses resulting in stool concentrations in mice similar to those measured in humans. The mice were challenged with 10(5) CFU of orogastric VRE or ESBL-Kp on day 2 of treatment and concentrations of the pathogens in stool were monitored. The impact of drug exposure on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. In comparison to saline controls, oral vancomycin promoted establishment of high-density colonization by VRE and ESBL-Kp in stool (8 to 10 log10 CFU/g; P < 0.001), whereas fidaxomicin did not (<4 log10 CFU; P > 0.5). Vancomycin treatment resulted in significant reductions in enterococci, Bacteroides spp., and Clostridium leptum, whereas the population of aerobic and facultative Gram-negative bacilli increased; deep-sequencing analysis demonstrated suppression of Firmicutes and expansion of Proteobacteria during vancomycin treatment. Fidaxomicin did not cause significant alteration of the microbiota. In summary, in contrast to vancomycin, fidaxomicin treatment caused minimal disruption of the intestinal microbiota and did not render the microbiota susceptible to VRE and ESBL-Kp colonization.

Clinical and economic benefits of fidaxomicin compared to vancomycin for Clostridium difficile infection.

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.

Do Inflammatory Bowel Disease Patients Have Difficulty Tapering Off of Oral Vancomycin?

Introduction: Antibiotic therapy has demonstrated efficacy in the short and long-term treatment of inflammatory bowel disease (IBD) colitis, however broad spectrum antibiotics may predispose to C. difficile infection (CDI). Oral vancomycin has been used successfully in the treatment of CDI in IBD, but patients frequently relapse after short course (14 day) therapy. There is limited data regarding prolonged use of this antibiotic beyond 2 weeks in IBD patients with and without CDI. We describe patterns of oral vancomycin treatment in a prospective IBD cohort, focusing on individuals who required prolonged treatment. Methods: Prescriptions for oral vancomycin in consented IBD patients from a prospective natural history registry were identified between 2009 and 2012. Individuals with oral vancomycin treatment beyond 3 months formed the study population (v-IBD). Demographic, clinical, and treatment parameters were characterized in each v-IBD study patient and compared with 5 non-vancomycin exposed IBD matched controls. Results: Of 1,748 IBD registry patients, 160 (9.2%) received oral vancomycin between 2009 and 2012 (vancomycin exposed). Vancomycin was used for >4 weeks in 68 individuals (42.5% of vancomycin exposed IBD) and 26 patients (16.2% of vancomycin exposed) received vancomycin for >3 months (v-IBD group). The duration of treatment in v-IBD patients ranged from 3.5-60 months. In the v-IBD patients, 20 (76.9%) were on vancomycin continuously for >6 months, 15 (57.7%) for >12 months, 8 (33.3%) for >24 months and 5 (19.2%) for >36 months. In the v-IBD group, 57.7% were female compared to 54.6% female in the control IBD subgroup (p=NS). There was no difference in disease subtype in v-IBD (57.7% Crohn’s disease) and controls (55.4% Crohn’s disease). All v-IBD patients demonstrated benefit from treatment based on improvement in SIBDQ scores. One-third of the v-IBD patients were diagnosed with CDI prior to oral vancomycin initiation. When compared with IBD controls (n=130), v-IBD patients (n=26) required more prednisone (84.6% vs. 37.7%; p<0.001), but demonstrated similar rates of immunomodulator use (48.5% vs. 65.4%; p=0.135), and anti-TNF biologic treatment (38.5% vs. 57.7%; p<0.083). No infections with vancomycin resistant bacteria were noted in the v-IBD patients. Conclusion: Oral vancomycin use is common in IBD with 1 in 11 patients receiving this antibiotic over 4 years. Among vancomycin treated IBD patients >40% received treatment for at least 1 month continuously. A subgroup of refractory IBD patients who had high rates of steroid, immunomodulator, and anti-TNF use benefited from maintenance oral vancomycin beyond 3 months. Prospective evaluation of oral vancomycin in IBD patients is warranted.

Assessment of treatment patterns and patient outcomes before vs after implementation of a severity-based Clostridium difficile infection treatment policy

National guidelines recommend oral vancomycin for severe Clostridium difficile infection (CDI) based on results from recent clinical trials demonstrating improved clinical outcomes. However, real-world data to support these clinical trials are scant. To compare treatment patterns and patient outcomes of those treated for CDI before and after implementation of a severity-based CDI treatment policy at a tertiary teaching hospital. This study evaluated adult patients with a positive C. difficile toxin before and after implementation of a policy where patients with severe CDI given metronidazole were switched to oral vancomycin unless contra-indicated. Patients were stratified according to disease severity using a modified published severity score. Treatment patterns based on CDI severity and rates of refractory CDI were assessed. In total, 256 patients with CDI (mean age 66 years, standard deviation 17, 52% female) were evaluated (before implementation: N = 144; after implementation: N = 112). Use of oral vancomycin for severe CDI increased significantly from 14% (N = 8) to 91% (N = 48) following implementation of the policy (P < 0.0001). Refractory disease in patients with severe CDI decreased significantly from 37% to 15% following implementation of the policy (P = 0.035). No significant differences were noted among patients with mild to moderate CDI. A severity-based CDI treatment policy at a tertiary teaching hospital increased the use of oral vancomycin and was associated with decreased rates of refractory CDI.

Evaluation of Oral Vancomycin Use for the Treatment of Clostridium Difficile-Associated Disease and Risk Factor Analysis of Treatment Failure

Evaluation of Oral Vancomycin Use for the Treatment of Clostridium Difficile-Associated Disease and Risk Factor Analysis of Treatment Failure

Clostridium difficile outbreaks: prevention and treatment strategies

The incidence and severity of Clostridium difficile infection (CDI) have increased dramatically over the past decade. Its treatment, however, has largely remained the same with the exception of oral vancomycin use as a first-line agent in severe disease. From 1999 to 2004, 20,642 deaths were attributed to CDI in the United States, almost 7 times the rate of all other intestinal infections combined. Worldwide, several major CDI outbreaks have occurred, and many of these were associated with the NAP1 strain. This ‘epidemic’ strain has contributed to the rising incidence and mortality of CDI. The purpose of this article is to review the current management, treatment, infection control, and prevention strategies that are needed to combat this increasingly morbid disease.

Lack of Increased Colonization with Vancomycin-Resistant Enterococci during Preferential Use of Vancomycin for Treatment during an Outbreak of Healthcare-Associated Clostridium difficile Infection

To assess whether use of oral vancomycin for treatment during an outbreak of Clostridium difficile infection (CDI) was associated with increased rates of colonization with vancomycin-resistant enterococci (VRE). A retrospective analysis of hospital databases. The Jewish General Hospital in Montreal, Quebec, Canada. We collected data regarding VRE colonization and CDI from November 1, 2000, through September 30, 2007, during which policies of preferential oral metronidazole or vancomycin treatment were implemented to control an outbreak of CDI. Four periods were considered: period 1, the preoutbreak period when metronidazole was used; period 2, the CDI outbreak period when metronidazole was used; period 3, the postoutbreak period when vancomycin was used; and period 4, the postoutbreak period when metronidazole was used. A total of 2,412 cases of CDI and 425 cases of VRE colonization were identified. The rate of CDI increased significantly during period 2 and decreased to preoutbreak levels during period 3. The rate of VRE also increased during period 2 and decreased during the first 18 months of period 3. A clonal outbreak of cases of VRE (VanA) colonization was observed toward the end of period 3 and into period 4. Excluding the period of the clonal outbreak, there was a strong correlation between the number of cases of CDI and VRE colonization (r=0.736; P=.001) and a negative association between VRE colonization and vancomycin use (r=-0.765; P=.04). Increased vancomycin use was not associated with an increase in VRE colonization over a 2-year period. Restriction of vancomycin use during CDI outbreaks because of the fear of increasing VRE colonization may not be warranted.

Clostridium Difficile Infection in the “Oldest” Old: Clinical Outcomes in Patients Aged 80 and Older

Clostridium difficile infection (CDI) represents a cause of substantial morbidity, particularly for older adults. Although older age is a risk factor for CDI, few studies have specifically focused on clinical outcomes in older adults, particularly the "oldest" old. Retrospective review. University of Michigan Health System. All patients aged 80 and older with a positive cytotoxin assay for C. difficile and a clinical course consistent with CDI during 2006. Clinical data were recorded, including comorbid conditions and treatment regimens, as well as outcomes, including treatment failure, infection relapse, and 90-day mortality. Seventy patients aged 80 and older (mean 84.0+/-4.1) with CDI were identified. Metronidazole was given as initial therapy in 65 (92.8%); 18 of these 65 (27.7%) experienced treatment failure, requiring subsequent use of oral vancomycin. Serious adverse events included three episodes of toxic megacolon, two requiring colectomy. One death was directly attributable to CDI. All-cause mortality was 8.6% at 30 days and 17.1% at 90 days. Higher white blood cell (WBC) counts were independently associated with treatment failure (P=.02) and coronary artery disease with 90-day mortality (P=.02). In older adults with CDI, treatment failure on metronidazole occurred frequently and was associated with higher WBC count. Larger prospective studies are needed to determine risk factors for treatment failure and relapse in order to develop better paradigms for CDI treatment in older adults. Initial therapy with vancomycin may be appropriate for elderly patients, especially those with elevated WBC counts.

An elderly woman with 'Red Man Syndrome' in association with oral vancomycin therapy: a case report

Introduction'Red Man Syndrome' is a recognized adverse reaction to intravenous vancomycin therapy. This case concerns an elderly woman who developed a 'Red Man Syndrome' reaction whilst on oral vancomycin therapy for Clostridium difficile (C difficile) diarrhoea. Isolated case reports exist recording this reaction in association with oral vancomycin therapy in patients with inflammatory bowel conditions or impaired renal function, of which this patient had both.Case PresentationAn 82 year old Caucasian woman who developed C. difficile diarrhoea after co-amoxiclav therapy for a urinary tract infection. She was treated with oral vancomycin therapy during which she developed a widespread erythematous rash in keeping with that of 'Red Man Syndrome'. This rash resolved on stopping the oral vancomycin.ConclusionThis case is important in the light of the increasing use of oral vancomycin to treat C. difficile diarrhoea, a rising problem in the UK. It also calls us to review our understanding of the mechanism of the 'Red Man Syndrome' reaction. It is possible that significant absorption of orally administered vancomycin occurs in the presence of an inflammatory bowel condition.

Sudden increase of vancomycin-resistant enterococcal infections in a Korean tertiary care hospital: possible consequences of increased use of oral vancomycin.

A sudden increase in vancomycin-resistant enterococci (VRE) infections was noted in 1998 in a tertiary care hospital in Korea. All of the VRE isolated in 1998 in the hospital were VanA type and most were multidrug-resistant Enterococcus faecium. The increase in VRE was probably due to the increased use of oral vancomycin to treat Clostridium difficile infections and clonal as well as horizontal spread. More restricted oral vancomycin use and stricter infection control measures are required to achieve a better control of the spread of VRE.

Sudden increase of vancomycin-resistant enterococcal infections in a Korean tertiary care hospital: possible consequences of increased use of oral vancomycin

Sudden increase of vancomycin-resistant enterococcal infections in a Korean tertiary care hospital: possible consequences of increased use of oral vancomycin

Risk factors for vancomycin-resistant Enterococcus (VRE) infection in colonized patients with cancer.

To determine the risk factors for vancomycin-resistant Enterococcus (VRE) infection in colonized patients with cancer, we conducted a case-control study. According to multivariate analysis, the only significant factors were neutropenia (< 500 cells/mm3) for more than 1 week and the use of oral vancomycin. Therefore, colonized neutropenic patients with cancer who have previously used oral vancomycin are most prone to VRE infection.

Clostridium difficile–associated disease : Implications for midwifery practice

Clostridium difficile–associated disease (CDAD), a gastrointestinal infection with a wide range of manifestations whose primary symptom is diarrhea, occurs when antibiotic medications, or rarely other drugs or conditions, disrupt the normal colonic microflora, making it susceptible to the growth of toxigenic C difficile. It is a significant nosocomial infection and an increased incidence has been noted in recent years. Although infrequently seen in midwifery practices, it does occur and may increase with the growing usage of intrapartal antibiotics. Midwives may evaluate and treat a client with an initial episode of mild to moderate CDAD; they also may manage collaboratively or refer for medical management those clients with recurrent or severe disease. This article reviews the epidemiology, pathogenesis, clinical presentation, prevention, and midwifery management of initial and recurrent CDAD. The limitation in the use of oral vancomycin due to the emergence of vancomycin-resistant enterococcus, resulting in metronidazole becoming the primary agent for treatment of CDAD, and the implications of this in the treatment of CDAD during pregnancy and lactation are addressed.

ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease.

ASHP supports preferential use of oral metronidazole for treating CDAD when antimicrobial therapy is indicated. Oral vancomycin should be reserved for severe, potentially life-threatening cases or when oral metronidazole cannot be used. Oral metronidazole is as safe and effective as oral vancomycin and is considerably less costly. In addition, preliminary data suggest that routine use of oral vancomycin for CDAD may contribute to the spread of VRE--emerging nosocomial pathogens that can be extraordinarily difficult to treat. Pharmacists should work to foster preferential prescribing of oral metronidazole for the treatment of CDAD. Pharmacists should also actively seek opportunities to educate health care providers and counsel patients about the risks associated with the indiscriminate use of vancomycin and other antimicrobial agents.

Is there a relationship between vancomycin-resistant enterococcal infection and Clostridium difficile infection?

The relationship between vancomycin or metronidazole treatment of Clostridium difficile-associated diarrhea (CDAD) and the occurrence of vancomycin-resistant enterococcus (VRE) infection was investigated by review of 18 case-control studies. Fifteen (83%) of 18 studies found vancomycin use, days of use, or grams used to be significantly associated with VRE infection or colonization. Intravenous vancomycin use was a significant risk in nine of 10 studies, and oral vancomycin use was a significant risk in three of four studies that stratified risk by route of administration. Although statistically associated, oral vancomycin use was so infrequent (25% in the study with the most use) that it is likely to have only a minor influence as a risk for VRE infection or colonization when compared with the much more widespread use of intravenous vancomycin. Metronidazole exposure was found to be a significant risk in four of five studies that specifically assessed this variable, but the indication for metronidazole use was not specified. Risk factors for both VRE infection and CDAD include antimicrobial exposure, number of antimicrobials, days of antimicrobial use, specific agents (third-generation cephalosporins, clindamycin, and imipenem), patient age, length of hospitalization, severity of underlying illness, use of electronic rectal thermometers, enteral feedings, environmental contamination, and contamination of the hands of health care workers.