Probable hypersensitivity reaction to vancomycin associating rash, fever and neutropenia

We describe the case of a 54-year old woman with breast cancer who was treated by vancomycin for febrile neutropenia due to a methicillin-resistant Staphyloccocus epidermidis infection of a surgically implanted catheter. She developed an hypersensitivity reaction to vancomycin associating neutropenia, fever, skin rash and elevated liver enzymes following re-challenge with vancomycin after having been misdiagnosed with septic thrombophlebitis. Following this re-challenge, neutrophils count fell dramatically but promptly resolved after cessation of vancomycin.     

IgE-mediated reaction to vancomycin and teicoplanin after treatment with vancomycin.

A 38-year-old male patient developed severe signs of type 1 allergy after treatment with vancomycin. By the basophil histamine release test, the patient's isolated basophil leucocytes were shown to react IgE dependent after challenge with vancomycin and teicoplanin. This indicates that the patient is type 1 allergic towards vancomycin and teicoplanin.     

Relapse of antibiotic associated colitis: endogenous persistence of Clostridium difficile during vancomycin therapy.

This study reports 24 patients with antibiotic associated colitis due to Clostridium difficile. Fifteen patients were treated with vancomycin due to the severity of the colitis and in eight of these a clinical relapse of the colitis occurred after vancomycin therapy was stopped. Bacteriological investigations of these patients indicated that C difficile was able to persist in stool samples during vancomycin therapy in the absence of detectable cytotoxin. This was in contrast with the seven patients successfully treated with vancomycin without relapse, and those not treated with vancomycin where both stool cultures and cytotoxin assays became negative. These results suggest that patients being treated with vancomycin for antibiotic associated colitis due to C difficile should have stool cultures done during and after treatment. Persistence of the organism in the absence of detectable cytotoxin may identify those patients who relapse and lead to either recommencement of vancomycin or alternative therapeutic approaches.     

Vancomycin-induced neutropenia resolves after substitution with teicoplanin.

Neutropenia is an uncommon adverse effect associated with prolonged vancomycin therapy. Neutrophil counts normally recover after discontinuation of vancomycin in this situation, but treatment options are needed for those patients who require ongoing antibiotic therapy. We describe a case of vancomycin-induced neutropenia in which the neutropenia resolved after vancomycin was replaced by the structurally related compound teicoplanin.     

Ventriculitis due to a hetero strain of vancomycin intermediate Staphylococcus aureus (hVISA): successful treatment with linezolid in combination with intraventricular vancomycin

A 67-year male presented with relapse 14 days after treatment with vancomycin for a MRSA ventriculitis. CSF samples taken at the time of relapse grew MRSA with a MIC for vancomycin of 4 mg/L by E-test and therapy with linezolid (600 mg bd) and intraventricular vancomycin (20 mg od) was initiated. Using the macrodilution E-test, the isolate was found to have sub-populations with a MIC for vancomycin of 8 mg/L and teicoplanin of 12 mg/L and a population analysis profile almost identical to the hVISA strain MU3, indicative of a hVISA strain. Concentrations of vancomycin in the CSF over the period of therapy ranged from 25.6-192.5 mg/L after intraventricular administration and those of linezolid ranged from 3.4-6.7 mg/L after intravenous administration, exceeding the MICs for this isolate. The patient made a successful recovery, with no further episodes of ventriculitis at 1-year follow-up. We report the first case of ventriculitis due to hVISA. It was successfully treated with intrathecal vancomycin and intravenous linezolid. We also believe this to be the first documented case of clinical infection due to hVISA in South Africa.     

Recurrent Clostridium difficile-associated colitis responding to cholestyramine

We describe a patient with relapses of Clostridium difficile cytotoxin-positive pseudomembranous colitis (PMC) after treatment with vancomycin, a course of metronidazole and a trial of bacitracin. She remains free of disease after a prolonged course of cholestyramine. We suggest there may be a role for anion-exchange resins in patients with PMC relapsing after vancomycin therapy.     

Systemic absorption of oral vancomycin in patients with Clostridium difficile infection

Oral vancomycin is utilized in the treatment of severe Clostridium difficile infection (CDI). We prospectively measured serum vancomycin concentrations (SVC) in patients treated with oral vancomycin. The SVC was measured by immunoassay prior to, and at least 3 days after, the administration of oral vancomycin 125 mg every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty-seven patients with a mean age of 74 y (± 18) were enrolled. There was no detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 μg/ml that was not detectable on subsequent testing. The severity of the CDI and/or renal failure did not have an effect on SVC. Orally administered vancomycin at 125 mg 4 times daily was not absorbed from the gastrointestinal tract.     

Vancomycin-induced thrombocytopenia

Vancomycin-induced thrombocytopenia has only been reported once previously in the medical literature. We describe a patient in whom sudden severe reversible thrombocytopenia developed on two separate occasions after exposure to vancomycin hydrochloride. A 54-year-old man was admitted to the hospital for bilateral swelling and erythema of his extremities. At the time of admission he received 2 days of vancomycin therapy without incident. On day 14 he was reexposed to vancomycin and thrombocytopenia developed, with a nadir value of 17 x 10(9)/L. On day 30, a single dose of vancomycin was administered, and thrombocytopenia once again developed, with a nadir value of 11 x 10(9)/L. Hematologic cytopenias are infrequent adverse effects of vancomycin therapy. It is postulated that these effects may be due to an immunologically mediated mechanism. With the increasing use of vancomycin due to the emergence of methicillin-resistant Staphylococcus aureus, this case should alert clinicians to this rare but potentially lethal manifestation of vancomycin.     

Oral antibiotics as a novel therapy for arthritis: evidence for a beneficial effect of intestinal Escherichia coli

OBJECTIVE: The intestinal flora is thought to play an important role in regulation of immune responses. We investigated the effects of changing the intestinal flora on the course of adjuvant-induced arthritis (AIA) and on experimental autoimmune encephalomyelitis (EAE) by the use of oral antibiotics. METHODS: Oral treatment with either vancomycin or vancomycin, tobramycin, and colistin was started after AIA and EAE induction. Clinical symptoms of AIA and EAE were monitored, and microbial analysis of ileal samples was performed. RESULTS: Oral vancomycin treatment after disease induction significantly decreased clinical symptoms of AIA. Simultaneously, increased concentrations of Escherichia coli were detected in the distal ileum of vancomycin-treated rats. Ileal concentrations of E coli were inversely related to disease scores in rats with AIA. Coadministration of colistin/tobramycin to prevent the increase in E coli abrogated the beneficial effect of vancomycin on AIA. Vancomycin treatment also reduced the clinical symptoms of EAE. CONCLUSION: We propose oral vancomycin as a novel therapeutic strategy in autoimmune diseases.     

Vancomycin use in pediatric neurosurgery patients

OBJECTIVE: The objective of this article is to describe a pediatric neurosurgery patient population receiving vancomycin and examine the indications for and appropriateness of vancomycin use. METHODS: A cross-sectional study was performed on the pediatric neurosurgery patients at Egleston Children's Hospital who received vancomycin from January 1 through December 31, 1996. Vancomycin use was compared with the Centers for Disease Control and Prevention Hospital Infection Control Practices Advisory Committee recommendations for vancomycin use. RESULTS: Thirty patients received 115 doses of vancomycin. The median patient age was 8.0 years, and 17 (56.7%) were male. Vancomycin was used for prophylaxis in 28 (93.3%) patients and empiric therapy in 3 (10.0%) patients; one patient received vancomycin for surgical prophylaxis followed by empiric therapy for suspected meningitis. Vancomycin prophylaxis was initiated after the incision in 6 (21.4%) patients and was continued as prophylaxis for more than one dose in 26 (92.9%) patients. CONCLUSIONS: Vancomycin was used primarily as surgical prophylaxis in pediatric neurosurgery patients, and use was not consistent with the Hospital Infection Control Practices Advisory Committee recommendations. These data suggest that for certain subpopulations, such as pediatric neurosurgery patients, there is a need for more specialized recommendations. Furthermore, prudent vancomycin use is warranted to successfully decrease the risk of further emergence of vancomycin resistance. Because vancomycin use may be prevalent in this population, assessment of vancomycin use in pediatric neurosurgery patients followed by establishment of vancomycin clinical guidelines may help improve the appropriateness of vancomycin use in this population.     

Treatment of Clostridium difficile colitis and diarrhea with vancomycin

Toxigenic Clostridium difficile is the major cause of antibiotic-associated colitis and is susceptible to vancomycin at fecal concentrations achieved with oral therapy. The effect of oral vancomycin was studied in 16 patients with C. difficile-related diarrhea or colitis, 12 of whom had colitis documented by endoscopy, biopsy, and/or barium enema. Four patients had antibiotic-associated diarrhea and possibly antibiotic-associated colitis, because sigmoidoscopy either showed normal results (two patients) or was not performed (two patients). Nineteen episodes of diarrhea were treated with oral vancomycin in two dosage regimens for three to 14 days. Twelve patients received 2 g daily, and four patients initially received 1 g or less per day. Within 48 hours of the start of vancomycin therapy, 14 of 16 patients (87 percent) showed a decrease in temperature, abdominal pain and diarrhea. Diarrhea ceased completely within two days of the start of vancomycin in nine episodes, within three to seven days in six episodes, and within eight to 14 days in the remaining four episodes. Diarrhea recurred in two of these patients (12 percent) when the drug inciting the initial episode of colitis was given again 42 days or more after vancomycin therapy was stopped; both patients responded again to retreatment with vancomycin. Oral vancomycin is an effective treatment of C. difficile-related colitis and diarrhea.     

Bacteremia due to Clostridium difficile

We describe a case of bacteremia due to Clostridium difficile, which was successfully treated by intravenous vancomycin. A 69-year-old woman was admitted to our hospital because of third degree burn injuries. She was treated with cefazolin for two weeks followed with flomoxef for one week before the operation (debridement and grafting of skin). On the third postoperative day high fever (temperature 40 degrees C), abdominal pain and severe watery diarrhea developed. Antibiotic-associated colitis with bacteremia was diagnosed presumptively, flomoxef was stopped, and oral and intravenous therapy with vancomycin was started. A blood culture taken before the administration of vancomycin yielded C. difficile accompanied with Enterococcus faecalis and Enetrococcus casseliflavus. A stool culture taken on the next day yielded C. difficile, and a stool latex agglutination test was also positive. The patient improved slowly. Parenteral vancomycin was discontinued after two weeks. One week later, the patient developed pneumonia, and imipenem/cilastatin was added. Soon after addition of the agent, she developed recurrent diarrhea despite continual oral vancomycin therapy. The fecal samples obtained at this time were positive for C. difficile by culture and positive for toxins A & B. She was satisfactorily treated with oral vancomycin for a total of four weeks. After the following two weeks, however, recurrence of diarrhea developed again, which rapidly decreased with oral vancomycin for seven days. The patient did well thereafter and was discharged. All three C. difficile isolates from blood and fecal specimens were positive for toxins A & B, and identified the same PCR ribotyping pattern.     

Susceptibility to vancomycin of methicillin-resistant Staphylococcus aureus isolated in a university hospital in Japan

Intravenous vancomycin was approved in 1991 in Japan and has been widely used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Consequently, ever since the initial discovery of vancomycin intermediate-resistant S. aureus in Japan, the vancomycin resistance of this organism has been a great concern in clinical settings. We investigated whether vancomycin resistance had emerged in MRSA isolated in our hospital since the approval of the use of intravenous vancomycin. Vancomycin susceptibility was evaluated on the basis of minimum inhibitory concentrations determined by the agar dilution method and a heterogeneous resistance examination. The median minimum inhibitory concentration of the 69 MRSA strains isolated in 1988 and the 74 isolated in 1998 was 0.75 microgram/ml and 1.0 microgram/ml, respectively (p < 0.001), however, all of the strains were classified in the susceptible group. None of them was an MRSA heterogeneously resistant to vancomycin (hetero-VRSA), which has been defined as a strain having a 1/10(6) or greater heterogeneously resistant subpopulation to vancomycin. In another set of investigations, no hetero-VRSA were found among 12 other MRSA strains isolated after intravenous administration of vancomycin for 14 or more days (range: 14 to 77 days). We conclude that while the use of intravenous vancomycin may have slightly lowered the vancomycin susceptibility of MRSA in our hospital, the decrease in so small that it may not be significant clinically. In addition, no hetero-VRSA were found in our hospial.     

Acute vancomycin-dependent immune thrombocytopenia as an anamnestic response

Drug-related thrombocytopenia is a well-described but relatively rare complication of antibiotic therapy. In this entity, platelet destruction is immune-mediated, often resulting in a precipitous drop in platelet count over a short period of time. Most of these cases of thrombocytopenia are drug-dependent, as discontinuation of the offending agent frequently results in a timely return to baseline, pre-exposure platelet levels. We report the case of a 61-year-old male patient receiving vancomycin and ceftazidime for lower extremity wet gangrene who experienced a marked, acute reduction in platelet count 12 to 15 hours after starting antibiotic therapy. There was no readily apparent clinical or laboratory explanation for his thrombocytopenia. Pre- and post- antibiotic serum samples were preserved and sent for drug-dependent platelet antibody analysis. The pre-exposure specimen revealed the presence of IgG vancomycin-dependent platelet antibodies, while the post-exposure specimen demonstrated both IgG and IgM vancomycin-dependent platelet antibodies. Ceftazidime-dependent platelet antibodies were not identified in either sample. These findings indicate prior sensitization to vancomycin, with subsequent acute production of IgM anti-platelet antibodies after re-exposure to the antibiotic. The patient's antibiotics were held after the acute-onset of thrombocytopenia with subsequent restoration of normal platelet counts within 4 days of drug withdrawal, and the patient at no time experienced significant adverse bleeding events. Antibiotic therapy with vancomycin is a rare and perhaps overlooked cause for new-onset thrombocytopenia in hospitalized patients. This case illustrates that the development of severe thrombocytopenia within hours of vancomycin administration does not rule out drug-related immune clearance, as the rapid platelet destruction may indicate an anamnestic antibody response to the drug after previous exposure. In such a scenario, immediate discontinuation of vancomycin is recommended to improve platelet counts. From a laboratory perspective, retrieval of serum both pre- and post-administration of vancomycin is most helpful in determining a patient's drug-immunization status and can help guide safe drug use during future infections.     

Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of vancomycin and metronidazole for eradication of asymptomatic Clostridium difficile fecal excretion as a means of controlling nosocomial outbreaks of C. difficile diarrhea. DESIGN: Randomized, placebo-controlled, non-blinded trial. SETTING: Six hundred-bed regional referral Veterans Affairs Medical Center. PATIENTS: Thirty patients excreting C. difficile without diarrhea or abdominal symptoms. INTERVENTIONS: All patients were randomized to receive 10 days of oral vancomycin, 125 mg four times daily; metronidazole, 500 mg twice daily; or placebo, three times daily. MEASUREMENTS: Stool cultures were obtained during treatment and for 2 months after treatment. All C. difficile isolates were typed by restriction endonuclease analysis (REA). RESULTS: Clostridium difficile organisms were not detected during and immediately after treatment in 9 of 10 patients treated with vancomycin compared with 3 of 10 patients treated with metronidazole (P = 0.02) and 2 of 10 patients in the placebo group (P = 0.005). The fecal vancomycin concentration was 1406 +/- 1164 micrograms/g feces, but metronidazole was not detectable in 9 of 10 patients. Eight of the nine evaluable patients who had negative stool cultures after treatment with vancomycin began to excrete C. difficile again 20 +/- 8 days after completing treatment. Three of these patients received additional antibiotics before C. difficile excretion recurred, and five acquired new C. difficile REA strains. Four of six patients who received only vancomycin before C. difficile excretion recurred were culture-positive at the end of the study compared with one of nine patients who received only placebo (P = 0.047). CONCLUSIONS: Asymptomatic fecal excretion of C. difficile is transient in most patients, and treatment with metronidazole is not effective. Although treatment with vancomycin is temporarily effective, it is associated with a significantly higher rate of C. difficile carriage 2 months after treatment and is not recommended.     

Pulmonary administration of perfluorodecaline- gentamicin and perfluorodecaline- vancomycin emulsions.

The aim of this study was to examine pharmacokinetics and pulmonary antibiotic tissue concentrations (PATC) of gentamicin and vancomycin after intrapulmonary administration of a perfluorodecaline (PFD)-gentamicin and a PFD-vancomycin emulsion during partial liquid ventilation (PLV). PLV was initiated in 19 healthy rabbits and 18 surfactant-depleted rabbits. The animals were randomized to receive either 5 mg/kg gentamicin and 15 mg/kg vancomycin intravenously, or 5 mg/kg gentamicin intrapulmonary, or 15 mg/kg vancomycin intrapulmonary. Antibiotic plasma levels were measured after 15, 30, 45, and 60 min, and hourly thereafter. After 5 h animals were sacrificed and lungs were removed to evaluate PATC and histology. PATC were significantly higher after intrapulmonary administration of both gentamicin and vancomycin. In healthy rabbits, peak plasma concentrations were lower and 5 h plasma concentrations were higher after intrapulmonary administration, whereas plasma concentrations were not different in surfactant-depleted rabbits. There were no differences in lung histology, hemodynamics, lung mechanics, or gas exchange between the treatment groups. We conclude that during PLV, higher PATC can be achieved after intrapulmonary administration of PFD-antibiotic emulsions compared with intravenous administration of the same dose without apparent short-term adverse effects. We speculate that intrapulmonary antibiotic administration during PLV may be beneficial in treating severe pneumonia.     

The importance of vancomycin in drug rash with eosinophilia and systemic symptoms (dress) syndrome

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome characterized by fever, rash, eosinophilia, atypical lymphocytes, and multiorgan involvement has a significant mortality. Inpatient vancomycin use is increasing and appears to be emerging as an important etiology of DRESS syndrome. This study highlights the importance of vancomycin as a cause of DRESS syndrome. We reviewed all cases of DRESS syndrome among inpatients consulted by the Allergy & Immunology service at Massachusetts General Hospital (MGH) from July 2009 through December 2010. We also reviewed the use of inpatient parenteral vancomycin over the past 4 years at MGH. Six patients fulfilled clinical criteria for DRESS syndrome, including rash, fever, eosinophilia, and hepatitis, with five (83%) having vancomycin as the attributable cause. Onset of symptoms varied from 12 days to 4 weeks after start of vancomycin treatment. Systemic findings included atypical lymphocytes, lymphadenopathy, nephritis, hypotension, tachycardia, and pharyngitis. Treatment with corticosteroids was required in three cases. Recurrence of peripheral eosinophilia was a marker of disease relapse. In three of the five patients (60%), elevated human herpesvirus 6 (HHV6) IgG titers correlated with greater systemic involvement and prolonged time to resolution. MGH pharmacy records indicate a progressive increase in the number of patients treated with parenteral vancomycin over the last 4 years. Causative agents for DRESS syndrome in an inpatient setting is likely different from that seen in the general population. With increasing use of vancomycin, we are likely to see more cases of DRESS syndrome caused by vancomycin. Recognition of vancomycin as a common cause of inpatient DRESS syndrome is important.     

Vancomycin: the need to suit serum concentrations in hemodialysis patients

The vancomycin dose for hemodialysis (HD) patients should be adjusted by monitoring drug serum concentrations. However, this procedure is not available in most health services in Brazil, which usually adopts protocols based on published studies. The trials available are controversial, and several have not been conducted with current dialyzers. This study aimed at assessing the suitability of vancomycin serum concentrations in HD patients at a public hospital. Blood samples of HD patients were collected from November 2006 to May 2007, at time intervals of 48, 96, 120, or 168 hours after vancomycin administration. Drug measurement was performed with polarized light immunofluorescence. Approximately 86% of trough vancomycin serum concentrations were below the recommended value, indicating exposure to subtherapeutic doses and a higher risk for selecting resistant microorganisms.     

Rifampin resistance. Development during the therapy of methicillin-resistant Staphylococcus aureus infection

The incidence of methicillin-resistant staphylococcal infections, for which vancomycin hydrochloride remains the only active cell-wall antibiotic therapy, is rising. Some physicians have been combining other antibiotics with vancomycin in hopes of obtaining a more effective regimen for the therapy of these infections. Rifampin has been advocated as a concurrent second antibiotic because of its extraordinary potent bactericidal activity for Staphylococcus aureus. When rifampin is used in combination with a cell-wall antibiotic, suppression of the development of rifampin resistance has been thought possible. We report a case of infection caused by a methicillin-resistant S aureus in which the rifampin resistance occurred during therapy with vancomycin and rifampin. The rifampin resistance was stable and was present after ten serial broth and agar passages. Physicians are cautioned against the indiscriminant or routine use of rifampin as a second antibiotic in combination with vancomycin for the therapy of infections caused by S aureus.     

军团菌肺炎合并耐甲氧西林表皮葡萄球菌败血症1例报告并文献复习

目的探讨军团菌肺炎合并耐甲氧西林表皮葡萄球菌（MRSE）败血症的临床诊断和治疗。方法报道1例军团菌肺炎合并MRSE败血症患者的诊治过程。结合文献复习,对军团军肺炎合并MRSE败血症的诊断和治疗进行讨论。结果骨髓穿刺培养报告为MRSE。用万古霉素3天后体温逐渐下降,9天后体温正常。3月5日至20日两次血清军团菌抗体检测显示LB1：8和LL1：8滴度升高4倍。结论军团菌肺炎合并MRSE败血症的临床确诊需结合军团菌肺炎诊断标准和血（骨髓）培养证实MRSE阳性,治疗须联合万古霉素和新大环内酯类或氟喹诺酮类抗菌药物。