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PubMed2000

Analysis of 42 cases of septicemia caused by an epidemic strain of methicillin-resistant Staphylococcus aureus: evidence of resistance to vancomycin.

Recent case reports of vancomycin treatment failures in the United States, Japan, and France have prompted a retrospective analysis of 42 cases of septicemia caused by epidemic methicillin-resistant Staphylococcus aureus strain 15 (EMRSA-15), which is the most prevalent epidemic strain of methicillin-resistant S. aureus in the United Kingdom; all cases occurred in a teaching hospital in Manchester, United Kingdom, between 1994 and 1998. Mortality was lowest (4%) in patients with rifampin-susceptible isolates treated with vancomycin and rifampin. It rose to 38% in patients who were treated with both antibiotics but in whom the organism became resistant to rifampin during therapy, and it reached 78% in patients who had rifampin-resistant isolates or in whom rifampin was contraindicated (P<.0001; Fisher exact test, 2-tailed). All isolates were susceptible to vancomycin by conventional laboratory testing, but susceptibility was lost by growth in vancomycin in vitro, becoming resistant at a minimum inhibitory concentration of 8 mg/L. This was associated with accumulation of cell-wall material. The deoxyribonucleic acid fingerprint remained unchanged. This study suggests that rifampin played a key role in the prevention of deaths caused by an epidemic strain of methicillin-resistant S. aureus that readily gave rise to a subpopulation with reduced susceptibility to vancomycin.

Animals↗

PubMed1999

Effect of parenteral antibiotic administration on persistence of vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract.

A mouse model of vancomycin-resistant Enterococcus faecium (VRE) intestinal colonization was used to study the effect of different subcutaneous antibiotics on persistence and density of VRE colonization. Gastric inoculation of a clinical VanB VRE isolate, in conjunction with oral vancomycin in drinking water (250 microgram/mL), resulted in high-level VRE colonization (mean, 9.5 log10 cfu/g) in all 169 experimental mice. After discontinuation of oral vancomycin, the level of VRE in the stool specimens of mice receiving subcutaneous saline steadily decreased (mean, 3.59 log10 cfu/g at day 19). Subcutaneous vancomycin, clindamycin, piperacillin-tazobactam, ticarcillin-clavulanic acid, metronidazole, cefotetan, ampicillin, and ampicillin-sulbactam all promoted persistent high levels of stool VRE. Subcutaneous ceftriaxone, cefepime, ciprofloxacin, and aztreonam promoted increased VRE density to a lesser degree or not at all. Thus, in a mouse model, vancomycin and antibiotics with potent antianaerobic activity promoted persistent high-density intestinal VRE colonization, whereas antibiotics lacking potent antianaerobic activity did not.

Animals↗

PubMed2004

Similar hematologic effects of long-term linezolid and vancomycin therapy in a prospective observational study of patients with orthopedic infections.

Linezolid is an alternative to vancomycin for the long-term treatment of gram-positive bacterial orthopedic infections because of its antibacterial spectrum and oral bioavailability, but duration-related myelosuppression could offset its advantages. To evaluate the hematologic effects of these agents, we prospectively studied 65 consecutive adults with gram-positive bacterial orthopedic infections requiring > or =2 weeks of vancomycin therapy (n=52) or linezolid therapy (n=20). Trends suggesting higher incidence of hematologic effects among the patients receiving vancomycin were not significant, regardless of whether the end point was lowest cell count during therapy or change from baseline. The only difference was a higher incidence of thrombocytopenia (<150x10(9) platelets/L) in the subset of the linezolid recipients who had received vancomycin within 2 weeks before starting linezolid therapy than in the linezolid recipients who had not received vancomycin (5 [71%] of 7 patients vs. 2 [15%] of 13; P=.02). All hematologic effects were reversible. In conclusion, hematologic effects were detectable through weekly monitoring and were reversible; therefore, concern about myelosuppression need not preclude linezolid use for orthopedic infections requiring long-term therapy.

Acetamides↗

PubMed1999

Enterococcal bacteremia: risk factors for vancomycin resistance and predictors of mortality.

OBJECTIVE: To identify risk factors for vancomycin resistance and mortality in enterococcal bacteremia. DESIGN: Historical cohort study. SETTING: A large academic medical center with a high prevalence of vancomycin-resistant enterococci (VRE). PATIENTS: Two hundred sixty patients with enterococcal bacteremia, of whom 72 (28%) had VRE. RESULTS: Independent risk factors for infection with VRE were the mean number of antibiotic days (P<.001), renal insufficiency (P<.001), mean days of vancomycin use (P = .005), and neutropenia (P = .013). A trend toward a significant association between metronidazole use and VRE also was noted (P = .068). Mortality was attributable to the bacteremia in 96 patients (37%). Severity of illness (P<.001) and age (P = .020) were independent risk factors for mortality. Vancomycin resistance was not, however, an independent predictor of mortality. CONCLUSION: These results suggest that restrictions on antibiotic use, particularly in patients with renal insufficiency and neutropenia, may help to combat the rising incidence of VRE. Although patients with VRE bacteremia demonstrated higher mortality rates than patients with infection due to susceptible isolates, vancomycin resistance was not an independent predictor of mortality in these patients and likely serves more as a marker of underlying severity of illness.

Adolescent↗

PubMed2006

Descriptive epidemiology and case-control study of patients colonized with vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus.

BACKGROUND: Patients colonized or infected with vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus may be at risk of acquiring vancomycin-resistant S. aureus if the vanA gene is transferred from vancomycin-resistant enterococcus to methicillin-resistant S. aureus. OBJECTIVE: Our goal was to identify risk factors for cocolonization or coinfection (CC/CI) with vancomycin-resistant enterococcus and methicillin-resistant S. aureus. DESIGN: We conducted a descriptive, epidemiologic study of all patients with CC/CI identified from January 1998 to May 2003 and a nested case-control study of a cohort of patients hospitalized in the burn and wound unit. SETTING: We conducted our study in a 813-bed tertiary care university teaching hospital. POPULATION: The study population consisted of patients found to have CC/CI during the study period. METHODS: Descriptive epidemiologic data were collected from hospital records of all patients identified as having CC/CI. A subset of patients hospitalized in the burn and wound unit were included in a case-control study. RESULTS: CC/CI was detected in 71% of the patients during a single hospital stay. The burn and wound unit, which does active surveillance for both organisms, and the general medicine unit, which does not do active surveillance for either organism, cared for more than one-half of these patients. Among patients being cared for in the burn and wound unit, having exposure to 2 or more invasive devices (central venous catheters, indwelling urinary catheters, and enteral feeding tubes) and renal insufficiency were independent risk factors for CC/CI. CONCLUSIONS: Patients with CC/CI are the population at greatest risk for vancomycin-resistant S. aureus colonization or infection. The number of invasive devices to which patients are exposed and, thus, possibly the patients' underlying severity of illness, as well as renal insufficiency, appear to be risk factors for CC/CI.

Adult↗

PubMed1998

Epidemiology, appropriateness, and cost of vancomycin use.

Pharmaceutical costs, which approach $40 billion annually, account for about 8% of health care costs. Prescription drugs represent 5% to 20% of the total hospital budget, and antimicrobials account for 20% to 50% of hospital pharmaceutical costs. At one university hospital, the percentage of patients receiving antimicrobials increased from 31.8% in 1988 to 53.1% in 1994. Receipt of vancomycin has been associated with the emergence of resistant enterococci and has resulted in Centers for Disease Control and Prevention (CDC) recommendations for its use. Studies show that vancomycin use is increasing, that dosing is often inappropriate, that certain populations (such as oncology, neurosurgery, and cardiovascular surgery patients) are more likely to receive vancomycin, and that often use is not consistent with CDC recommendations. Few studies have assessed the cost of vancomycin use; those that have show that it is costly. Further studies of vancomycin use are needed, so that use can be improved through focused educational programs.

Adult↗

PubMed1999

Prevalence of vancomycin-resistant enterococci among children with end-stage renal failure. Mid-European Pediatric Peritoneal Dialysis Study Group.

To evaluate the prevalence of colonization with vancomycin-resistant enterococcus (VRE) in end-stage renal failure (ESRF), we screened the intestinal flora from 338 pediatric ESRF patients treated in 13 pediatric nephrology units in mid-Europe. Eighty-one patients were undergoing hemodialysis, 66 were undergoing chronic peritoneal dialysis, and 191 were transplant recipients. A total of 363 enterococcal strains were recovered from 232 patients. Twenty-seven enterococcal strains from 24 patients (7.1%) had reduced susceptibility to vancomycin (minimal inhibitory concentration [MIC], >4 microg/mL). Although two patients (0.6%) carried enterococci with high-level resistance to vancomycin (MIC, >32 microg/mL; i.e., VRE), strains of enterococcus with reduced susceptibility to vancomycin (ERSV) were recovered from the other 22 subjects. Past use of vancomycin (P = .05) and tacrolimus therapy (P = .011) were independent risk factors for ERSV or VRE carriage. Enterococcal infections occurred with a similar frequency among enterococcal carriers and noncarriers; no infections with VRE or ERSV were reported. In conclusion, the prevalence of ERSV carriage and the rate of VRE colonization among mid-European children and adolescents with ESRF currently are moderate and low, respectively.

Adolescent↗

PubMed1992

A cluster of vancomycin-resistant Enterococcus faecium in an intensive care unit.

OBJECTIVE: To describe the epidemiology of a cluster of vancomycin-resistant Enterococcus faecium (VAREC) in a cardiothoracic surgery intensive care unit. DESIGN: A case series of patients identified through review of surveillance data on nosocomial infections, review of microbiologic records, and culture survey of patients in the unit. RESULTS: Six patients in the cardiothoracic surgery intensive care unit had VAREC with identical antimicrobic susceptibility patterns over a 6-month period. Four patients were identified with VAREC through prospective surveillance and 2 through retrospective review. Prior vancomycin use was seen more commonly in patients with VAREC (6/6, 100%) than in those without VAREC (3/12, 25%) (Fisher's exact test, p = .01). Six of the 7 patients with prior infection developed VAREC (85.7%). A prior nosocomial infection and prior exposure to vancomycin were found to be important variables in a logistic regression analysis. VAREC also was isolated from the environment. A combination of cohorting of patients and staff, and modifications of standard contact isolation practices eliminated the presence of VAREC from the cardiothoracic surgery intensive care unit. CONCLUSIONS: The results suggest that prior administration of vancomycin, especially in the patient who develops nosocomial infection, can influence the acquisition of vancomycin-resistant enterococci and that VAREC may be transmitted from patient to patient. Using a modification of the standard infection control practice of isolation, we were able to control the spread of this resistant strain of E faecium.

Cross Infection↗

PubMed1998

Failure to eradicate vancomycin-resistant enterococci in a university hospital and the cost of barrier precautions.

OBJECTIVE: To describe the effect of infection control interventions on the incidence of vancomycin-resistant enterococci (VRE), the utility of pharyngeal cultures for surveillance for VRE colonization, and the cost of barrier precautions. DESIGN: Evaluation of the occurrence of VRE infection or colonization, rates of vancomycin use, results of surveillance cultures before and after interventions, and the cost of increased barrier precautions. SETTING: University of Massachusetts Medical Center, a 347-bed tertiary-care teaching hospital with eight intensive-care units, one burn unit, and one bone marrow transplant unit. PARTICIPANTS: Patients in the intensive-care units and staff who were involved with patients colonized or infected with VRE. METHODS: Infection control interventions included placement of patients with VRE in private rooms, strict contact isolation, cohorting of patient and nursing staff, prohibiting of equipment sharing, and monitoring of compliance with the vancomycin restriction policy, with hand washing, and of the adequacy of environmental cleaning. Both rectal and pharyngeal cultures were obtained from patients at the beginning of the outbreak, and the utility of pharyngeal cultures was evaluated. The cost of barrier precautions was estimated by comparing the cost of glove and gown use before and after the outbreak began. RESULTS: The interventions decreased the number of new cases of VRE, but total eradication of VRE was not achieved. Compliance with the room-cleaning protocol was 91% (141/155 observations). Hand washing following interaction with patients who were not in isolation was 51%, vs 100% for patients in isolation. Overall, handwashing compliance was 71% (319/449): 56% (130/231) for physicians and 86% (187/218) for nurses (P<.0001). The mean number of doses of vancomycin dispensed per 1,000 patient days decreased from 145 to 114 per 1,000 patient days (P<.001). Compliance with vancomycin-use guidelines was 85%. Forty-six (77%) of 60 surveillance rectal swabs yielded enterococci, as compared to only 4 (11%) of 36 pharyngeal cultures (P<.0001). Expenses on glove and gowns alone increased by over $11,000 per year since the epidemic began. CONCLUSIONS: Implementation of the various infection control measures did not eradicate VRE cases from the hospital. Rectal cultures were more useful than pharyngeal cultures for surveillance of VRE. Controlling VRE epidemics can be costly.

Cross Infection↗

PubMed2003

Effect of linezolid versus vancomycin on length of hospital stay in patients with complicated skin and soft tissue infections caused by known or suspected methicillin-resistant staphylococci: results from a randomized clinical trial.

BACKGROUND: Complicated skin and soft tissue infections are common surgical indications usually requiring patients to be hospitalized, and are often caused by gram-positive bacteria, including methicillin-resistant staphylococci such as MRSA. Vancomycin has been the standard treatment for methicillin-resistant staphylococcal infections in many countries, but its intravenous-only formulation for systemic infections often confines patients to the hospital for the treatment. Linezolid, a novel oxazolidinone antibiotic available in intravenous and 100% bioavailable oral forms, was shown in a randomized trial to be as efficacious as vancomycin for suspected or proven methicillin-resistant staphylococcal infections. To determine if oral linezolid can reduce length of hospital stay (LOS) when compared to vancomycin, we compared the LOS for the 230 complicated skin and soft tissue infection patients enrolled in this trial. MATERIALS AND METHODS: Patients received up to four weeks of linezolid (intravenous followed by optional oral) or vancomycin (intravenous only), followed by up to four weeks of observation. Unadjusted LOS was estimated using Kaplan-Meier survival functions, whereas the log-logistic survival analysis model was used to estimate the multivariate-adjusted LOS controlling for patient demographics and selected baseline clinical variables. Analysis was done on the intent-to-treat (n = 230) sample as well as on two subsamples of the clinically evaluable (n = 144) and surgical site infection (n = 114) patients. RESULTS: The unadjusted Kaplan-Meier median LOS was five days shorter for the linezolid group than the vancomycin group in the intent-to-treat sample (9 vs. 14 days, p = 0.052). It was eight days shorter (8 vs. 16 days, p = 0.0025) in the clinically evaluable sample, but the difference in the surgical site infection sample was not significant (10 vs. 14 days; p = 0.29). The linezolid group's unadjusted mean LOS was 1.7, 5.3 and 0.8 days shorter in the intentto-treat, clinically evaluable, and surgical site infection samples, respectively. After adjusting for age, gender, race, geographic region, bacteremia, type of inpatient location, and number of concurrent medical conditions using the log-logistic model, between-treatment differences in the multivariate-adjusted median LOS decreased to 3, 6, and 3 days, whereas the differences in mean LOS increased to 3.1, 6.5 and 2.5 days for the intent-to-treat, clinically evaluable, and surgical site infection samples (p < 0.01, < 0.01, and < 0.10), respectively. When the between-treatment differences in LOS were expressed as odds ratio of hospital discharges, multivariate-adjustment increased the odds ratios in favor of linezolid for all the three samples. CONCLUSION: Results from this randomized trial show that linezolid can significantly reduce LOS for patients with complicated skin and soft tissue infections from suspected or confirmed methicillin-resistant staphylococci.

Acetamides↗

PubMed1993

Levels of vancomycin in aqueous humor after topical eye drops administration.

Vancomycin is an antibiotic which is especially active against Gram positive bacteria. At present, numerous infections of the anterior segment of the eye are caused by the Staphilococcus aureus and epidermis. Strains which are resistant to methicilin are more and more frequent and for this reason Vancomycin is becoming the antibiotic of choice to combat these infections since no resistance of the Staphilococcus to it has been demonstrated. The authors evaluated the levels of Vancomycin in aqueous humor after the administration of topical eye-drops. For the first two hours after the last administration, levels of 0.52 micrograms/ml were detected. These inhibit the growth of the majority of bacteria sensitive to Vancomycin. Between two and four hours, the levels decreased to 0.15 micrograms/ml; these are therapeutic levels for a large number of Gram positive bacteria. From four hours after the last administration, these levels are undetectable. Due to the success of its penetration, topical administration of Vancomycin should be considered as a therapeutic modality against infections by gram positive bacteria of the anterior segment. The ideal guideline for administration would be one drop every two hours, especially if the infection is severe. In this way, subconjunctival injection could be avoided.

Anterior Eye Segment↗

PubMed1999

Interspecies recombination between enterococci: genetic and phenotypic diversity of vancomycin-resistant transconjugants.

Handwerger and colleagues demonstrated that a particular clinical isolate of Enterococcus faecium, designated GUC, and here redesignated as GUCR, can conjugatively transfer vancomycin resistance. The vancomycin resistance is encoded by a chromosomally born linked set of genes in the donor, designated the vanA cluster, to the chromosome of an E. faecalis recipient, JH2-2. Here it is reported that an earlier isolate of E. faecium from the same patient who later harbored the vancomycin-resistant E. faecium GUCR lacks the vanA gene cluster but is otherwise similar (by SmaI chromosomal fingerprint and metabolic fingerprinting) to the vancomycin-resistant GUCR. Therefore, "GUCS" is a strong suspect as the base strain for the clinical acquisition of the vanA cluster present in GUCR. Thirteen laboratory-generated vanA transconjugants derived from conjugation between GUCR and JH2-2 were subjected to further analysis, allowing a comparison between transfer in the laboratory and transfer that occurred in the clinical setting. Surprisingly, each JH2-2 transconjugant had a unique constellation of abilities to oxidize various members of a panel of potential carbon sources. This pattern was stable for each transconjugant, and it was not changed by growing the strains with or without vancomycin. Transconjugants had pulsed-field gel electrophoretic (PFGE) patterns largely consistent with that of JH2-2, the recipient in conjugation experiments. However, PFGE analysis showed that a large but variable amount of DNA, between 145 kb and 277 kb, was transferred into different transconjugants. The mechanism appears to be conjugative transposition in which new DNA is added to the pre-existing genome rather than substituting for a segment in the recipient. Mapping and hybridization studies of several transconjugants showed that each received similar, but not exactly the same, DNA fragment of at least 30 kb from the donor. Sequencing of 16S ribosomal genes was used to confirm that the recipient and donor strains used in transconjugation experiments were different species. Sequence analysis was also used to consider the possibility that rRNA operons might be mobilized in conjugation, but no evidence for the transfer of rDNA operons was found. An apparent insertion sequence in E. faecium almost identical to IS 1485 and 57% sequence identity to IS 199 of Streptococcus mutans was found in the region of DNA transferred. The results imply new consequences of conjugative transfer and interspecies recombination.

Anti-Bacterial Agents↗

PubMed1999

Comparison of direct and enrichment methods for the selective isolation of vancomycin-resistant enterococci from feces of pigs and poultry.

Isolation results of vancomycin-resistant enterococci (VRE) of fecal samples from pigs and broiler and layer chickens obtained with two vancomycin-supplemented enrichment media, kanamycin aesculin azide (KAA) broth and Enterococcosel (ECC) broth, and three isolation media, KAA agar, ECC agar, and Slanetz and Bartley (SL) agar, were compared. Direct isolation on vancomycin-containing agar plates was not efficient in swine and layer chickens, which had only low numbers of VRE. In broilers chickens, the VRE content of the samples was high, and SL as well as ECC were found to perform better than KAA agar. The same three agar media were used as selective plating media after 1 and 2 days incubation of the samples in KAA and ECC enrichment broths. Sensitivities of the 12 different enrichment-plate combinations tested ranged from 0 to 81% in layer chickens and from 5 to 44% in samples from pigs. In the high prevalence type of samples from broilers, sensitivities still varied substantially from 52 to 78%. Incubating vancomycin-containing enrichment broths for 2 days compared with 1 day was favorable for the isolation of vancomycin-resistant Enterococcus faecalis, E. gallinarum, and E. casseliflavus but not for E. faecium and E. hirae/E. durans. ECC broth and ECC plates yielded the highest number of E. gallinarum and E. casseliflavus. In layer as well as in broiler chickens, ECC broth incubated for 2 days and plated on ECC agar was the most sensitive method. In pigs, however, KAA broth incubated for 2 days and plated on ECC medium yielded the highest number of VRE.

Animals↗

PubMed1999

Inactivation of the methicillin resistance gene mecA in vancomycin-resistant Staphylococcus aureus.

Acquisition of high-level resistance to vancomycin in the laboratory mutant VM50 (vancomycin MIC increased from 1.5 to 100 microg/ml) was accompanied by the appearance of a heterogeneous phenotype and a virtual loss in methicillin resistance: in most cells of cultures of VM50 the methicillin MIC of the parental strain was reduced from 800 to 1.5 microg/ml with only a subpopulation (10(-5)) retaining methicillin resistance at near the parental level (MIC of 400 microg/ml). Interestingly, the vancomycin MIC of this subpopulation was less (25 microg/ml) than that of VM50 (100 microg/ml). A similar antagonism between methicillin and vancomycin resistance levels was observed upon introduction of an intact mecA into VM50 on a plasmid vector: methicillin resistance of the majority of cells increased from 1.5 to 100 microg/ml while the vancomycin MIC declined from 100 to 12/25 microg/ml. Membrane preparations from mutant VM50 showed no detectable penicillin-binding protein (PBP) 2A by the fluorographic assay. Sequencing of the mecA gene resident in mutant VM50 indicated the presence of a 19-bp duplication between nucleotide residues 280-298, leading to the generation of a stop codon TAA starting at nucleotide position 286.

Anti-Bacterial Agents↗

PubMed1998

Stability of vancomycin in an extemporaneously compounded ophthalmic solution.

The stability of vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution at -10, 4, 25, and 40 degrees C was studied. Vancomycin power was reconstituted with sterile water for injection to a concentration of 50 mg/mL. Artificial tears solution containing 0.3% hydroxypropyl methylcellulose, 0.1% dextran 70, 0.01% benzalkonium chloride, and 0.05% edetate disodium was used to produce a final concentration of 31 mg/mL. Triplicate solutions for each storage temperature and sampling time were prepared. The solutions were stored at -10, 4, 25, and 40 degrees C. Samples were taken initially and at 3, 7, 10, 21, 30, 45, and 60 days for visual inspection and analysis by high-performance liquid chromatography. All solutions remained clear and colorless at -10, 4, and 25 degrees C throughout the study period. By day 3, crystalline particles formed in the solutions stored at 40 degrees C. No substantial change in pH was observed at any time. At -10 degrees C, the solutions retained more than 90% of their initial vancomycin concentrations throughout the study period. The solutions retained a mean of at least 90% of the initial drug concentration for 21 days at 4 degrees C and for 7 days at 25 degrees C. For the solutions stored at 25 or 40 degrees C, less than 85% of the initial vancomycin concentration remained after 10 and 3 days, respectively. Vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution was stable for 45 days at -10 degrees C, 10 days at 4 degrees C, and 7 days at 25 degrees C in the tears solution's original container.

Anti-Bacterial Agents↗

PubMed1995

Vancomycin-resistant Enterococcus faecium bacteremia: risk factors for infection.

We describe an outbreak of vancomycin-resistant Enterococcus faecium (vanA phenotype) bacteremia on the oncology ward of a tertiary care community hospital. In 10 of the 11 cases the patients had leukemia and were neutropenic (median duration of neutropenia, 21 days) at the time of bacteremia. On average, patients received six antibiotic agents for a total of 61 agent-days prior to development of vancomycin-resistant E. faecium bacteremia. The mortality rate was 73%. Molecular typing of 22 isolates revealed that the majority (83%) represented a common strain, indicating nosocomial spread. When the 11 cases were compared to 22 matched control patients, gastrointestinal colonization with vancomycin-resistant E. faecium (odds ratio [denominator, 0] infinity, P = .005) and the use of antimicrobial agents with significant activity against anaerobes (metronidazole, clindamycin, and imipenem; odds ratio infinity, P = .02) were found to be risk factors for the development of vancomycin-resistant E. faecium bacteremia. Since no proven therapy for such infection exists, there is an urgent need to identify effective measures to prevent and control the development of vancomycin-resistant E. faecium bacteremia.

Adult↗

PubMed1996

Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea.

We conducted a prospective, randomized study to compare the efficacy of oral fusidic acid, oral metronidazole, oral vancomycin, and oral teicoplanin for the treatment of Clostridium difficile-associated diarrhea. Treatment resulted in clinical cure for 94% of the patients who were treated with vancomycin, 96% of those treated with teicoplanin, 93% of those treated with fusidic acid, and 94% of those treated with metronidazole. Clinical symptoms recurred in 16% of patients treated with vancomycin, 7% of those treated with teicoplanin, 28% of those treated with fusidic acid, and 16% of those treated with metronidazole. There was asymptomatic carriage of C. difficile toxin in 13% of patients treated with vancomycin, 4% of those treated with teicoplanin, 24% of those treated with fusidic acid, and 16% of those treated with metronidazole. No adverse effects related to therapy with vancomycin or teicoplanin were observed. Considering the costs of treatment, our findings suggest that metronidazole is the drug of choice for C. difficile-associated diarrhea and that glycopeptides should be reserved for patients who cannot tolerate metronidazole or who do not respond to treatment with this drug.

Administration, Oral↗

PubMed1989

Influence of antihistamine pretreatment on vancomycin-induced red-man syndrome.

Twelve adult male volunteers participated in a double-blind study to determine the effect of pretreatment with histamine and/or histamine2 receptor antagonists on the incidence and severity of vancomycin-induced "red-man syndrome." Subjects received hydroxyzine, 50 mg, ranitidine, 300 mg, hydroxyzine plus ranitidine, or placebo at weekly intervals 2 h before a l-h infusion of vancomycin, 1,000 mg. The extent of erythema was evaluated by burn chart and pruritus was assessed by each subject using a rank scale; symptoms were thus classified a priori as mild, moderate, or severe and their summation determined a global severity score for red-man syndrome. There was no significant intrasubject variation between area under the concentration-time curves for histamine and vancomycin (P greater than .05). Pretreatment with hydroxyzine alone provided significant protection against vancomycin-induced erythema and pruritus (P less than .05) whereas the effect of ranitidine did not differ significantly from placebo. The combination of hydroxyzine and ranitidine offered no advantage over hydroxyzine alone. Similar results were observed for global severity scores. Thus in normal volunteers prior administration of a histamine antagonist (hydroxyzine) provided significant protection against vancomycin-induced red-man syndrome compared to that afforded by placebo. There was no significant benefit from the histamine antagonist alone or by its addition to a histamine antagonist.

Double-Blind Method↗