A 62-year-old man with new-onset bullae.

Cutaneous blisters and/or bullae can occur in autoimmune disorders, infections, genetic diseases, and drug hypersensitivity. We present the case of a 62-year-old man with two autoimmune conditions who was admitted for antibiotic treatment of a lower extremity infection and suddenly developed a bullous rash. His physical examination was significant for tense, bullous lesions that involved his chin, palms, and inner thighs. Narrowing the differential diagnosis for patients with blistering skin lesions is imperative for timely and appropriate management.

Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial.

Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in all subjects. Although antibiotics did not alter absolute anti-RV IgA titers, RVV immunogenicity was boosted at 7 days in the narrow-spectrum group. Further, antibiotics increased fecal shedding of RV while also rapidly altering gut bacterial beta diversity. Beta diversity associated with RVV immunogenicity boosting at day 7 and specific bacterial taxa that distinguish RVV boosters and RV shedders were identified. Despite the negative primary endpoint, this study demonstrates that microbiota modification alters the immune response to RVV and supports further exploration of microbiome manipulation to improve RVV immunogenicity.

Drug-induced immune hemolytic anemia associated with anti-vancomycin complicated by a paraben antibody.

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is rare, but potentially life-threatening. A high index of clinical suspicion is required for diagnosis, since the number of medications known to induce DIIHA continues to expand. Additionally, in vitro antibody reactivity against reagent additives has been reported, which may complicate test interpretation. CASE REPORT: A 61-year-old group A, D+ woman with a history of negative antibody detection tests developed hemolytic anemia on Postoperative Day 7 after repeat incision and drainage of a chronically infected right knee prosthesis. She was treated with multiple antibiotics in the postoperative period, including three cephalosporins and vancomycin intravenously as well as vancomycin and gentamicin-containing intraarticular cement spacers. STUDY DESIGN AND METHODS: A workup for possible DIIHA was performed. Testing was performed using vancomycin and cephalosporin antibiotics. Initially, gentamicin injection solution was used for testing, followed by testing with its component ingredients. RESULTS: A vancomycin antibody was detected and anemia resolved after vancomycin was discontinued. Reactivity was seen when gentamicin injection solution was used for testing, raising the possibility of a gentamicin antibody as well. However, testing with purified gentamicin as well as methylparaben and propylparaben demonstrated a paraben antibody that reacted with the paraben-containing gentamicin solution. The patient also demonstrated an anti-N. Neither the paraben antibody nor the anti-N appeared to cause in vivo hemolysis. CONCLUSION: This is the second reported case of DIIHA associated with anti-vancomycin. It is the fourth report describing a paraben antibody.

Vancomycin-induced Immune Thrombocytopenia Proven by the Detection of Vancomycin-dependent Anti-platelet Antibody with Flow Cytometry.

Vancomycin-induced thrombocytopenia is a rare adverse reaction that may be overlooked because no specific diagnostic test is currently available. We herein report a patient with vancomycin-induced immune thrombocytopenia who was diagnosed by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. An IgG antibody in the patient's serum reacted with platelets only in the presence of vancomycin. Severe thrombocytopenia gave rise to life-threatening gastrointestinal bleeding, which was quickly resolved after effective platelet transfusion following the cessation of vancomycin administration. This report suggests that the flow cytometric test is useful for the differential diagnosis of thrombocytopenia and platelet transfusion should be performed after the cessation of vancomycin administration.

Treatment of enterococcal peritonitis with intraperitoneal daptomycin in a vancomycin-allergic patient and a review of the literature.

BACKGROUND: Intraperitoneal (IP) administration of antibiotics is a mainstay of therapy in the treatment of peritoneal dialysis-related peritonitis. The therapeutic options against gram-positive organisms in patients intolerant to vancomycin are limited. METHODS: This case report and review of the literature used a search of PubMed with the terms "daptomycin," "intraperitoneal," and "peritoneal" for 2004 through 7 February 2013 to find relevant publications. RESULTS: In addition to our patient, we identified 6 case reports of IP daptomycin for the treatment of peritonitis. Our patient was treated with a 14-day course of IP daptomycin, with resolution of signs and symptoms of peritonitis. She presented again 7 weeks later with signs and symptoms of peritonitis and was treated with a repeat course of IP daptomycin. Among the 6 patients reported in the literature, 4 received loading doses of daptomycin. Daptomycin 20 mg per liter of dialysate was administered in 4 patients, and the other 2 patients received higher doses based on body weight (milligrams per kilogram). Treatment duration averaged 10 or 14 days. In all 6 cases, clinical cure was reported. CONCLUSIONS: Although limited to case reports, the available literature suggests that IP daptomycin is a viable alternative for peritoneal dialysis-related peritonitis. However, routine use of this agent must be cautioned, because further prospective studies are required.

Piperacillin and vancomycin induced severe thrombocytopenia in a hospitalized patient.

In hospitalized patients with complex medical problems on numerous drugs, thrombocytopenia may have a multiple confounding etiology. Keeping this in mind, it is of utmost importance to monitor the platelet count regularly during hospitalization and on subsequent follow-up visits, even after the most probable etiology has been identified/most likely causative drug has been withdrawn. Isolated thrombocytopenia with no evidence of microangiopathic hemolysis on the peripheral blood smear in an acutely ill hospitalized patient implicated sepsis, disseminated intravascular coagulation and drugs as the most probable causes. Our patient represents an uncommon case of antibiotic-induced severe immune thrombocytopenia, as he developed both vancomycin-dependent and piperacillin-dependent antibodies, while being treated for cellulitis (vancomycin-specific antibodies of the IgG isotype, and both IgG and IgM antibodies specific for piperacillin were identified in laboratory testing). Vancomycin was stopped before the reports were available. Following this, the patient's platelet count showed a transient upward trend, but then the thrombocytopenia worsened drastically reaching a nadir of 10,000/µL. The platelet count returned to normal only after piperacillin/tazobactam was stopped after a week, thus establishing it as the cause of the more severe thrombocytopenia, which occurred later on; this was subsequently confirmed by the laboratory results. Vancomycin is an established cause of drug-induced immune thrombocytopenias, especially in acutely ill, hospitalized or elderly patients, whereas incidents of piperacillin/tazobactam-induced immune thrombocytopenia are uncommon. In case clinical suspicion is high, workup should include immunoprecipitation and flow cytometry studies to confirm antiplatelet antibodies.

[Enzyme immunoassay for the determination of the glycopeptide antibiotic eremomycin].

An indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed using rabbit polyclonal antibodies against the eremomycin-glucose oxidase conjugated antigen. This technique allows the glycopeptide antibiotic eremomycin to be determined both in aqueous solutions (with a sensitivity as high as 0.1 ng/ml) and in blood plasma. The cross-reactivity of the antibodies with vancomycin was 0.4% of that for eremomycin, while teicoplanin was almost not recognized. Experiments with blood plasma samples diluted 1:10 showed that the assay was linear over the concentration range 1-30 ng/ml and that the variation coefficient did not exceed 10%. The high sensitivity and selectivity of this test make it suitable for pharmacokinetic studies and drug monitoring analysis.

Resumenes de articulos de la literatura pediatrica: vancomicina en combinación con otros antimicrobianos en el tratamiento de infecciones graves por staphylococcus aureus meticilino-resistente / Abstracts of articles in the pediatric literature: vancomycin in combination with other antimicrobials in the treatment of serious infections due to methicillin-resistant staphylococcus aureus

La vancomicina frecuentemente es combinada con otros antimicrobianos debido a su deficiencia en el tratamiento de infecciones graves por Staphylococus aureus meticilino resistente (MRSA).

Infección nosocomial por Enterococcus: Hospital de San José, 2005 - 2007 / Nosocomial infections by Enterococci at the San Jose Hospital

Objetivos: describir las características epidemiológicas, clínicas, sociodemográficas y desenlace final de los pacientes adultos atendidos en el Hospital de San José con infección nosocomial por Enterococcus sp, los sitios anatómicos más comprometidos, el perfil de sensibilidad antimicrobiana y la presencia de resistencia a la vancomicina, así como determinar la mortalidad global en esta patología. Métodos: analizar los aislamientos positivos de Enterococcus sp en pacientes de 18 años o más, obtenidos de la base de datos LabPro del servicio de microbiología del Hospital de San José entre octubre de 2005 y diciembre de 2007; después seleccionar los aislamientos positivos de origen nosocomial, con base en los criterios establecidos por el CDC de Atlanta. Se recolectaron los datos clínicos, demográficos, y microbiológicos, así como la mortalidad de la población seleccionada. Resultados: de 303 aislamientos positivos para Enterococcus sp 58 fueron nosocomiales y el germen más frecuente fue el Enterococcus faecalis; 56,9% fueron mujeres y la edad promedio 50 años. Las comorbilidades específicas más comunes fueron hipertensión arterial, enfermedades neoplásicas y diabetes. El 74,1% de los pacientes eran manejados por servicios quirúrgicos y 91,4% del total fueron sometidos a algún procedimiento quirúrgico previo al aislamiento. La mortalidad fue 12%. Conclusiones: en nuestra población la infección nosocomial por Enterococcus sp corresponde al 19% del total de positivos para este germen. La especie más frecuente es el Enterococcus faecalis, que puede relacionarse con la alta sensibilidad encontrada a la vancomicina. Las penicilinas y los aminoglucósidos siguen siendo antibióticos de elección pues se identificó una alta sensibilidad en los antibiogramas. Se encontró una elevada resistencia a carbapenémicos, después del quinupristin/dalfopristin, explicado por la alta resistencia intrínseca del Enterococcus faecalis a este grupo antibiótico. La infección....

Objectives: to describe the epidemiological, clinical and socio-demographic features and the final outcome of adult patients diagnosed with a nosocomial infection by Enterococcus sp at the San José Hospital; to identify the most commonly involved anatomic sites; to describe the antibiotic sensitivity profile and the presence of vancomycin resistance; and to determine the overall mortality rate for this condition. Methods: all positive isolates of Enterococcus sp obtained from the LabPro database of the Department of Microbiology at the San José Hospital, between October 2005 and December 2007, in older than 18 year patients, were analyzed; positive isolates of nosocomial origin were selected based on the CDC criteria. Clinical, demographic and microbiological data, as well as, the mortality rate in the studied population were gathered in each case. Results: out of 303 positive isolates for Enterococcus sp, 58 were nosocomial and Enterococcus faecium was the commonest organism isolated; 56.9% were female patients and the mean age was 50 years. The most common specific comorbidities were arterial hypertension, neoplastic disease and diabetes. Of all participating patients, 74.1% were managed in surgical departments and 91.4% underwent a surgical procedure before the isolation of a microorganism. The mortality rate was 12%. Conclusions: we concluded that in our population, nosocomial infections caused by Enterococcus sp account for 19% of the total positive isolates for this agent. The most commonly isolated strain is Enterococcus faecium, which can be related to the high sensitivity to vancomycin identified. Due to the high level of sensitivity identified in antibiograms, penicillines and aminoglycosides continue to be the preferred antibiotics to treat these infections. In addition, we found a high resistance to carbapenemics, after administering quinupristin/dalfopristin, explained by the high intrinsic resistance of Enterococus faecium to this...

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.

Vancomycin-induced immune thrombocytopenia.

BACKGROUND: Vancomycin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms. We conducted a study to determine whether thrombocytopenia is caused by vancomycin-dependent antibodies in patients being treated with vancomycin. METHODS: We identified and characterized vancomycin-dependent, platelet-reactive antibodies in patients who had been referred for testing during a 5-year period because of a clinical suspicion of vancomycin-induced thrombocytopenia. We obtained clinical information about the patients from their referring physicians. RESULTS: Drug-dependent, platelet-reactive antibodies of the IgG class, the IgM class, or both were identified in 34 patients, and clinical follow-up information was obtained from 29 of these patients. The mean nadir platelet count in these patients was 13,600 per cubic millimeter, and severe bleeding occurred in 10 patients (34%). Platelet levels returned to baseline in all 26 surviving patients after vancomycin was stopped. In 15 patients, the drug was continued for 1 to 14 days while other possible causes of thrombocytopenia were investigated. Vancomycin-dependent antibodies were not found in 25 patients who had been given vancomycin and in whom thrombocytopenia did not develop. CONCLUSIONS: Severe bleeding can occur in patients with vancomycin-induced immune thrombocytopenia. The detection of vancomycin-dependent antiplatelet antibodies in patients receiving the antibiotic in whom thrombocytopenia develops, and the absence of antibodies in patients given the drug in whom platelet counts remain stable, indicate that these antibodies are the cause of the thrombocytopenia.

Successful vancomycin desensitization with a combination of rapid and slow infusion methods.

Vancomycin, an antibiotic to which methicillin-resistant Staphylococcus aureus (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the vancomycin infusion rate and/or premedicating with antihistamine effectively reduce hypersensitivity in most cases. However, vancomycin desensitization is sometimes the only way to ensure safe use. Two types of desensitization protocols have been reported, and these utilize different infusion intervals; rapid desensitization and slow desensitization. We herein report a case of vancomycin hypersensitivity with methicillin-resistant Staphylococcus aureus infection. A combination of the two desensitization protocols, rapid desensitization followed by slow desensitization, effectively inhibited the hypersensitivity reaction during vancomycin infusion, and methicillin-resistant Staphylococcus aureus was successfully eradicated.