Epidemiology of vancomycin-induced neutropenia in patients receiving home intravenous infusion therapy

BACKGROUND: Vancomycin is frequently used to manage serious resistant gram-positive infections. Neutropenia, whose epidemiology has not been well characterized, is a potentially serious adverse event associated with the use of vancomycin. OBJECTIVE: To characterize the incidence and risk factors for development of vancomycin-induced neutropenia in patients treated with home intravenous vancomycin therapy. METHODS: A retrospective chart review was conducted of adult patients receiving vancomycin therapy through the University of New Mexico Home Intravenous Infusion Clinic between January 1998 and December 2004. Data collection included demographics, comorbid conditions, dose and duration of vancomycin therapy, indications for vancomycin use, vancomycin concentrations, all concurrent medications, laboratory data, culture and susceptibility data, reasons for antibiotic alteration or discontinuations, all other recorded adverse events, management of adverse events, and outcomes of adverse events. RESULTS: A total of 372 charts of patients managed through the clinic were reviewed and 114 patients treated with vancomycin were identified. Fourteen (12%) cases of vancomycin-induced neutropenia were identified; 4 (3.5%) cases included a reduction in absolute neutrophil count to 500 cells/mm3 or less. The mean +/- SD duration of vancomycin therapy and time to neutropenia were 32 +/- 29 and 26 +/- 15 days, respectively. Laboratory monitoring was performed on a weekly basis and resolution of vancomycin-induced neutropenia occurred promptly after discontinuation. Total vancomycin doses used and serum concentrations were not associated with the development of neutropenia. CONCLUSIONS: Vancomycin-induced neutropenia may occur at a higher frequency than previously reported. Clinicians should monitor hematologic parameters at least weekly in patients receiving home intravenous vancomycin therapy.     

Valproic acid-induced neutropenia

OBJECTIVE: To report a case of severe neutropenia caused by valproic acid (VPA). CASE SUMMARY: A 56-year-old white woman with an infectious brain abscess causing tonic-clonic seizure activity was treated with VPA. She developed severe neutropenia after 2 days of VPA therapy. The absolute neutrophil count reached a nadir of 47 cells/mm(3) during VPA use and returned to normal upon its discontinuation. DISCUSSION: VPA is considered to be a well-tolerated antiepileptic drug. While neutropenia has been reported, it has been mild and transient. This patient developed severe neutropenia during effective treatment with VPA, making her significantly susceptible to infection. The Naranjo probability scale indicates VPA as the probable cause of neutropenia in this case. CONCLUSIONS: This report of severe neutropenia caused by VPA emphasizes the importance of monitoring complete blood cell counts during therapy with this agent.     

Tolerability of teicoplanin in 117 hospitalized adults with previous vancomycin-induced fever,rash, or neutropenia: A retrospective chart review

Background: Vancomycin has reliable antibacterial activity against many gram-positive pathogens but is associated with many adverse events. Teicoplanin, another glycopeptide, is associated with fewer adverse events, but its use in patients with previous vancomycininduced adverse reactions remains controversial.Objectives: The aims of this work were to evaluate the clinical characteristics of hospitalized patients with vancomycin-induced fever (ie, drug fever), rash, or neutropenia and to examine the tolerability of teicoplanin in these patients.Methods: This was a retrospective review of the medical charts of patients aged ≥18 years who were hospitalized between January 2002 and October 2007 at National Cheng Kung University Hospital in Tainan, Taiwan. Patients were included if they experienced drug-induced fever (ie, “drug fever”), rash, or neutropenia during vancomycin treatment. Their antimicrobial therapy was subsequently switched to teicoplanin. Clinical information and the development of drug fever, rash, or neutropenia with teicoplanin were determined from the charts.Results: Antibiotic therapy was switched to teicoplanin in 117 patients with vancomycin-induced fever alone (n = 24), rash alone (n = 77), both drug fever and rash (n = 8), or neutropenia (n = 8). The mean (SD) age of these patients was 53.1 (22.8) years, and 65 (56%) were male. The major clinical indications for vancomycin therapy among these patients were wound infections (21%), respiratory tract infections (14%), and bacteremia (13%). The dosages for vancomycin ranged from 1 g every 5 days to 1 g BID, and for teicoplanin ranged from 400 mg daily to 400 mg q72h, adjusted by the degree of renal dysfunction. Overall, 12 patients with vancomycin-induced fever (n = 2), rash (n = 6), or neutropenia (n = 4) subsequently developed teicoplanin-induced fever (n = 3), rash (n = 3), or neutropenia (n = 6). Specifically, of 8 patients with vancomycin-induced neutropenia, 4 (50%) subsequently developed neutropenia after switching to teicoplanin. Vancomycin- and teicoplanininduced neutropenia was often noted after 1 week of treatment. Among patients with vancomycin-induced fever, rash, or neutropenia, there were no differences between patients with or without teicoplanin-induced fever, rash, or neutropenia in terms of age, sex, weight, dosage or duration of vancomycin therapy, dosage of teicoplanin, or underlying disease. There was no difference in mortality rates between patients with or without teicoplanin-induced fever, rash, or neutropenia. The cause of all deaths was progression of infectious or underlying disease, unrelated to vancomycin or teicoplanin use.Conclusions: Based on this retrospective chart review of hospitalized patients with vancomycin-induced fever, rash, or neutropenia, only 10% experienced subsequent teicoplanin-induced fever, rash, or neutropenia. However, it should be noted that half of the patients with vancomycin-induced neutropenia developed teicoplanin-induced neutropenia.     

Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981.

A retrospective chart review of 98 patients treated with 100 courses of intravenous vancomycin was undertaken to better define its toxicity. Most of the patients carried diagnoses of Staphylococcus aureus or Staphylococcus epidermidis infection. Auditory toxicity was not seen, and fever and rash occurred in only 1 to 3% of the subjects. Phlebitis was noted in 13% of the cases and required discontinuation of therapy in 2%. Therapy was complicated by neutropenia (polymorphonuclear leukocyte count, less than or equal to 1,000 cells per cm3) in 2% of the patients but was rapidly reversible. Nephrotoxicity was uncommon (5%) and reversible in subjects receiving vancomycin alone, even when the therapy was continued. However, 35% of the patients receiving vancomycin with an aminoglycoside developed significant elevations in serum creatinine. Although this high incidence may have been due to the patient population selected or to the aminoglycoside therapy alone, the possibility of additive toxicity between vancomycin and the aminoglycosides should be considered.     

Vancomycin-induced elevation of liver enzyme levels

OBJECTIVE: To report a case of oral vancomycin-induced elevation of liver enzyme levels. CASE SUMMARY: A 57-year-old man with multiple medical conditions requiring systemic antibiotic therapy developed numerous Clostridium difficile-associated enterocolitis episodes. The patient did not respond adequately to oral metronidazole, as evidenced by his continuing diarrhea. He was treated with oral vancomycin on 5 separate occasions (with doses from 125 to 500 mg/day), each of which resulted in significant elevations in alanine aminotransferase (to 371 U/L) and aspartate aminotransferase (to 203 U/L) levels. The elevations resolved on each occasion with discontinuation of vancomycin. DISCUSSION: Vancomycin, a glycopeptide antibiotic, has primary activity against gram-positive bacteria. Oral vancomycin can be used for the treatment of C. difficile-associated enterocolitis in patients who fail to respond to or are intolerant to metronidazole therapy. Oral vancomycin has very poor bioavailability and, as of May 4, 2006, has not been associated with hepatic toxicity. Inflammatory bowel disease processes can result in increased absorption of oral vancomycin. CONCLUSIONS: This is the first reported case of oral vancomycin-induced elevation of hepatic enzyme levels. Use of the Naranjo probability scale indicated that this was a probable adverse drug-associated event.     

Transfusion‐related alloimmune neutropenia with no pulmonary complications: one donor—five cases

BACKGROUND: Neutrophil alloantibodies are well‐known triggers of transfusion‐related acute lung injury (TRALI) and also cause immune neutropenia. Alloimmune neutropenia due to transfusion is an isolated phenomenon that is only rarely identified. Its incidence is specified in the literature as being less than one in 10,000 transfused plasma‐containing units. We expect that this phenomenon is underreported. STUDY DESIGN AND METHODS: We observed five cases of alloimmune neutropenia with no respiratory complications with only one case initially reported as a suspected transfusion reaction. The other four cases were detected in the course of the subsequent lookback investigation. RESULTS: The first case was reported as a potential transfusion reaction when a female patient showed a decrease in the white blood cell count after a platelet (PLT) transfusion. Examinations of the donor blood revealed an antibody against the human neutrophil antigen HNA‐1b; the recipient was typed HNA‐1b positive and HNA‐1a negative. After examining the blood counts of other patients who previously received PLT concentrates from the same donor, we identified four other patients with an unreported decrease in the leukocyte and/or granulocyte count of more than approximately 50% after transfusion. CONCLUSION: HNA antibodies are generally regarded as potential triggers of TRALI. Here we describe an HNA antibody that reproducibly caused transfusion‐related neutropenia only without pulmonary complications. Factors predisposing patients to TRALI development are widely discussed. Our case suggests that antibody characteristics are also relevant in the development of TRALI. Current measures to prevent TRALI should also prevent transfusion‐related alloimmune neutropenia.     

Probable colchicine-induced neutropenia not related to intentional overdose

OBJECTIVE: To report a case of neutropenia caused by colchicine not associated with intentional overdose or with preceding severe gastrointestinal symptoms. CASE SUMMARY: A 68-year-old white man was admitted to the hospital with intractable pain from an acute attack of gout. The patient was treated with standard doses of oral colchicine for several days. He experienced mild loose stools, but no severe diarrhea or nausea during treatment. The patient then developed severe neutropenia, with an absolute neutrophil count of 240 cells/mm3. His white blood cell count returned to normal after discontinuing colchicine and administering filgrastim. DISCUSSION: Although colchicine is commonly associated with neutropenia in cases of intentional or accidental overdose, the patient developed this adverse effect after being treated with doses commonly used for the acute treatment of gout. In addition, this patient had taken low-dose colchicine for many years without experiencing hematologic adverse effects. CONCLUSIONS: Colchicine is often an attractive alternative to nonsteroidal antiinflammatory agents for the treatment of gout, especially in patients at risk for renal impairment or gastropathy. Our case illustrates that colchicine treatment can cause hematologic adverse effects; the clinician should monitor cell counts in patients receiving this agent, especially at the higher doses used for acute treatment of gout.     

High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy

What is known and Objective: Teicoplanin and vancomycin show similar clinical and bacteriological efficacy in clinical trials. Teicoplanin has been reported to have a lower adverse drug reaction (ADR) rate than vancomycin. Cross‐reactivity between these two glycopeptides is controversial. Our aim was to study the cross‐reactivity between teicoplanin and vancomycin through an assessment of all the reported ADRs of these drugs in our University hospital. Methods: Over a period of 2 years, 170 cases of vancomycin therapy, which were closely monitored by doctors and clinical pharmacists, were used to analyse ADRs. Teicoplanin therapy was used as an alternative in cases of vancomycin intolerance. When an ADR related to vancomycin or teicoplanin was suspected, specialists were consulted to confirm if these were true ADR and to determine whether the implicated drug should be stopped. All ADRs for the two glycopeptides were assessed for causality using the Naranjo probability scale. Results and Discussion: Thirty‐eight of 170 patients (22·4%) treated with vancomycin developed ADRs. Twenty‐four patients were switched to teicoplanin. However, 14 of those 24 patients (58·3%) developed ADRs. The time of onset of ADRs involving vancomycin was 12·7 ± 10·9 days (range, 1–46 days). The time of onset of sequential teicoplanin‐induced ADRs was 11·7 ± 4·7 days (range, 2–20 days). Of the 14 patients with ADRs related to sequential teicoplanin therapy, six showed cross‐reactivity between vancomycin and teicoplanin. The incidence of vancomycin‐induced neutropenia was 4·7% (8/170), whereas the incidence of teicoplanin‐induced neutropenia subsequent to vancomycin intolerance was as high as 33·3% (8/24). Furthermore, 71·4% (10/14) of the teicoplanin‐induced ADRs were associated with haematological abnormalities such as neutropenia, thrombocytopenia or leucopenia. What is new and Conclusion: Teicoplanin, used as an alternative in cases of vancomycin intolerance, was associated with a high incidence of ADRs and haematological reactions, most notably neutropenia. This high rate of ADRs suggests cross‐reactivity between the two glycopeptides.     

Treatment of carbimazole-induced agranulocytosis and sepsis with granulocyte colony stimulating factor

We present the management of agranulocytosis and neutropenic sepsis secondary to carbimazole with recombinant human granulocyte colony stimulating factor (G-CSF). A 72-year-old woman with a history of thyrotoxicosis presented with sore throat and fever two weeks after starting carbimazole. Investigations confirmed a leucopenia and neutropenia. G-CSF was used as an adjunctive therapy with discontinuation of carbimazole, barrier nursing and a broad-spectrum antibiotic regimen to treat her neutropenic sepsis. Total white cell count and neutrophil count returned to normal and she made an uneventful recovery. She was subsequently rendered euthyroid with radioiodine treatment.     

Life-threatening reaction to vancomycin given for noninfectious fever.

OBJECTIVE: To report a case of vancomycin-induced anaphylaxis (or anaphylactoid reaction) in a patient with a fever of unrecognized noninfectious origin. CASE SUMMARY: An 83-year-old white man, who was a patient of the Veterans Affairs Medical Center, developed a serious anaphylactic (or anaphylactoid) reaction while receiving intravenous vancomycin as empiric therapy for a nosocomial fever of unknown origin. The fever was subsequently proved to have been due to acute polyarticular gout rather than an infection. DISCUSSION: This patient developed respiratory distress and an increased serum troponin concentration, suggestive of a myocardial enzymatic leak as a result of vancomycin therapy. Vancomycin was given before the noninfectious cause of his fever was recognized. CONCLUSIONS: Even with cautious slow infusion, intravenous vancomycin can precipitate life-threatening infusion-related reactions in some patients. Because of this, and to reduce selective pressure for vancomycin resistance, sources of fever that do not require treatment with vancomycin should be diligently investigated prior to the institution of empiric vancomycin therapy in febrile patients, particularly when the past medical history is suggestive of an alternative diagnosis.     

A prospective study of neutropenia induced by high doses of beta-lactam antibiotics

A prospective study on the effect of beta-lactam antibiotics on granulopoiesis was carried out in 29 consecutive patients with bacterial endocarditis. Fourteen patients received a high dose of benzylpenicillin, up to 18 g/day, but in only three of them could the treatment be fulfilled as planned, for a mean time of 25 days. In 11 benzylpenicillin treated patients treatment had to be discontinued because of fever, rash or neutropenia. Neutropenia appeared in seven patients after 14-24 (mean 22) days. No superinfection occurred during the neutropenic phase which lasted 2-12 days. Patients with neutropenia differed significantly from others in having a lowered pretreatment neutrophil count (3.2 vs 10.4). In 15 patients treated with other beta-lactams, three cases of fever and rash and one case of neutropenia were seen in patients treated with cloxacillin 12 g daily. It was concluded that a daily dose of 18 g of benzylpenicillin is too high for longer treatment periods and that patients with initial low counts of neutrophils have an increased risk of developing neutropenia.     

Carbamazepine. What physicians should know about its hematologic effects

Transient leukopenia and, less commonly, neutropenia may occur with carbamazepine therapy. Discontinuation of therapy is usually not indicated unless symptoms are severe, persistent, or accompanied by infection. Patients with a low leukocyte or neutrophil count before treatment may be at increased risk for carbamazepine-induced leukopenia or neutropenia. Careful monitoring of blood counts, particularly during the first month of therapy, is essential. The frequency of monitoring can be determined on an individual basis. If a hematologic abnormality develops, the frequency of monitoring should be increased, especially if carbamazepine is not discontinued. Only when the neutrophil count falls below 500/mm3 does a severe risk of infection exist.     

Neutropenia Associated with Cephapirin Therapy

A case of neutropenia associated with cephapirin therapy is described. After discontinuation of cephapirin therapy, the neutrophil count returned to normal. Bone marrow examination revealed a marked reduction of polymorphonuclear leukocytes beyond the metamyelocyte stage and eosinophilia.     

Sensorineural hearing loss associated with intrathecal vancomycin

OBJECTIVE: To report a case of nonreversible bilateral sensorineural hearing loss resulting from administration of intrathecal vancomycin. CASE SUMMARY: A 63-year-old white man with newly diagnosed pre-B-cell acute lymphocytic leukemia developed Corynebacterium jeikeium meningitis associated with an Ommaya reservoir. The patient was treated with intravenous vancomycin for several days without symptomatic improvement, and intrathecal vancomycin was added to the treatment regimen. Difficulty in the patient's hearing was noted after the first intrathecal dose and he experienced complete hearing loss after the second intrathecal dose. An audiogram was performed and the patient was diagnosed with cranial nerve VIII bilateral sensorineural hearing loss. The Ommaya reservoir was removed and the patient was successfully treated with linezolid. DISCUSSION: Ototoxicity with intravenous vancomycin has been documented in multiple case reports, but this adverse effect has not been reported with intrathecal vancomycin. Cerebrospinal fluid vancomycin concentrations were not measured in our patient, but there was 1 documented occurrence of supratherapeutic serum vancomycin concentrations. Other drug-related causes of ototoxicity were evaluated and intrathecal vancomycin-induced ototoxicity was considered to be possible according to the Naranjo probability scale. CONCLUSIONS: The strong temporal relationship that was seen in this case suggests the possibility of an association between administration of intrathecal vancomycin and hearing loss. Healthcare providers should consider the potential for this adverse reaction with the intrathecal route of vancomycin administration.     

Desensitization protocols for vancomycin hypersensitivity.

OBJECTIVE: To discuss the pathophysiology of vancomycin-induced immediate hypersensitivity reactions, review the process of vancomycin desensitization, and provide specific directions for ordering and preparing rapid and slow desensitization protocols. DATA SOURCES: A MEDLINE search (1966-February 2001) of English-language literature pertaining to vancomycin desensitization and hypersensitivity reactions was performed. Tertiary sources were also used. DATA EXTRACTION: Published clinical studies and case reports. DATA SYNTHESIS: The pathophysiology of vancomycin-induced hypersensitivity reactions is discussed along with the procedure of vancomycin desensitization. Desensitization should be considered in Red Man syndrome (RMS) that does not respond to the usual treatment measures, and in vancomycin-induced anaphylaxis. Rapid desensitization is preferred as it is effective in the majority of patients and enables therapeutic dosing of vancomycin within 24 hours. In patients who fail rapid desensitization, a slow desensitization protocol may be tried. CONCLUSIONS: Vancomycin-induced immediate hypersensitivity reactions include RMS and anaphylaxis. Vancomycin desensitization should be considered for severe RMS reactions not responding to usual measures and in anaphylactic reactions to vancomycin, when substitution of another antbiotic is not feasible.     

Deterioration of previous acute lung injury during neutropenia recovery

DESIGN: Although neutropenia recovery is associated with a high risk of deterioration of respiratory condition, no studies designed to identify risk factors for acute respiratory distress syndrome (ARDS) in this situation have been published. SETTING: Medical ICU in a French teaching hospital. SUBJECTS: We conducted a study to describe critically ill cancer patients with ARDS during neutropenia recovery (defined as the 7-day period centered on the day the neutrophil count rose above 1000/mm3 [day 0]) and to compare them with critically ill cancer patients without ARDS during neutropenia recovery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a 10-yr period, 62 critically ill cancer patients recovered from neutropenia, of whom 21 experienced ARDS during neutropenia recovery, with a median time of -1 days (-2.5-1) between day 0 and ARDS. In-ICU mortality in these 21 patients was 61.9%. As compared with non-ARDS patients, ARDS patients were less likely to have myeloma and more likely to have leukemia/lymphoma treated with adriamycin, a history of pneumonia before neutropenia, and a neutropenia duration >10 days; they had a shorter time since malignancy diagnosis and a longer time from chemotherapy to neutropenia. Neither the leukocyte counts on day 0 nor those during the 6-day neutropenia recovery period were predictive of ARDS. CONCLUSIONS: Patients with acute respiratory failure after prolonged neutropenia complicated by pneumonia are at increased risk for ARDS.     

Levels of recombinant human granulocyte colony-stimulating factor in serum are inversely correlated with circulating neutrophil counts.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is effective in countering chemotherapy-induced neutropenia. However, serum rhG-CSF levels cannot be maintained throughout the course of rhG-CSF therapy. The drop in serum rhG-CSF levels may vary with the duration of rhG-CSF administration or with the circulating neutrophil counts. We investigated the relationship between serum G-CSF levels and circulating neutrophil counts and the pharmacokinetics of rhG-CSF for patients with lung cancer who had been treated with myelosuppressive chemotherapy and then with subcutaneous rhG-CSF (lenograstim, 2 micrograms per kg of body weight per day). Twelve patients were randomly assigned to four groups with different rhG-CSF therapy schedules. Serum G-CSF levels were measured by an enzyme immunoassay method. Serum G-CSF levels during the rhG-CSF therapy greatly exceeded endogenous G-CSF levels and were mainly due to the presence of exogenous rhG-CSF rather than increased levels of endogenous G-CSF. Despite the duration of rhG-CSF administration, serum G-CSF levels during rhG-CSF therapy were inversely correlated with circulating neutrophil counts (r2 = 0.73, P < 0.0001). The value for the area under the concentration-time curve of rhG-CSF on the day of neutrophilia was lower than that on the day of neutropenia (P < 0.05). Our results suggest that the fall in serum G-CSF levels during rhG-CSF therapy may result from increased clearance and/or decreased absorption of rhG-CSF, two processes related to circulating neutrophil counts.     

Zuclopenthixol-associated neutropenia and thrombocytopenia

OBJECTIVE: To report a case of neutropenia and thrombocytopenia secondary to use of zuclopenthixol in a schizophrenic patient. CASE SUMMARY: A 66-year-old white man with chronic schizophrenia was referred to the hospital due to neutropenia and thrombocytopenia that developed shortly after initiation of zuclopenthixol therapy. Prior to zuclopenthixol administration, his white blood cell and platelet counts were 8.5 x 10(9) cells/L3 and 305 cells x 10(9)/L, respectively. Progressive reduction in leukocyte and platelet counts occurred, reaching a nadir of 2.9 x 10(9) cells/L3 (granulocytes 18.9%) and 109 cells x 10(9)/L, respectively. Zuclopenthixol was discontinued on admission, resulting in complete recovery within the next five days. DISCUSSION: Neutropenia and thrombocytopenia are well-known complications of antipsychotic drug therapy. Zuclopenthixol, a well-established antipsychotic agent, has relatively few adverse effects. The rapid decrease of white blood cell and platelet counts following the initiation of zuclopenthixol, as well as the rapid recovery, implicate zuclopenthixol as the predominant cause for neutropenia and thrombocytopenia in this patient. CONCLUSIONS: Although neutropenia and thrombocytopenia are rare complications of zuclopenthixol therapy, monitoring blood counts in patients receiving this agent seems to be justified.     

Invasive aspergillosis in neutropenic patients: rapid neutrophil recovery is a risk factor for severe pulmonary complications

BACKGROUND: In invasive aspergillosis, the duration of neutropenia is an accepted risk factor, and recovery from neutropenia is generally associated with a favourable outcome. However, the rapidity of granulocyte recovery may rarely be associated with adverse sequelae. The purpose of this study was to define the relationship between neutrophil (polymorphonuclear, PMN) recovery after chemotherapy-induced bone marrow aplasia and the occurrence of severe pulmonary complications (haemoptysis, pneumothorax and death) in patients with haematological malignancies who developed invasive fungal pneumonias. METHODS: Twenty consecutive patients were retrospectively studied; eight of them had developed pulmonary events between 5 and 11 days after neutrophil recovery that followed deep neutropenia (PMN < 100 microL-1). RESULTS: Five patients had haemoptysis (one of these also had pneumothorax) and three had pneumothorax. According to the multiplicative logistic model, the odds of occurrence of a pulmonary event increased significantly with increasing PMN count on the fifth day (P < 0.001). Five of the eight patients who had pulmonary complications died. Also, the risk of death was larger in the presence of rapid neutrophil recovery, although the difference was not statistically significant (P = 0.111). Analysis of clinical and laboratory data showed that the risk of pulmonary complications significantly increased when the neutrophil concentration was > 4500 microL-1 on day 5 after deep granulocyte neutropenia (PMN < 100 microL-1). There was no correlation between pulmonary complications, dosage of amphotericin B and deaths. CONCLUSION: The occurrence of life-threatening complications in patients with invasive fungal pneumonia is closely related to rapid PMN recovery.     

Daptomycin (LY146032) treatment of experimental enterococcal endocarditis.

This study compared daptomycin (LY146032) with penicillin G procaine and vancomycin without and with gentamicin for treatment of experimental enterococcal endocarditis. The strain of Streptococcus (Enterococcus) faecalis used in this study was killed by daptomycin in vitro in broth but not in serum. In rabbits treated for 3 days, daptomycin significantly reduced bacterial counts of vegetations compared with no therapy but was significantly less effective than penicillin G procaine or vancomycin. Daptomycin-gentamicin significantly reduced bacterial counts of vegetations compared with daptomycin alone but was significantly less effective than vancomycin plus gentamicin. The efficacy of daptomycin-gentamicin did not differ significantly from that of penicillin G procaine-gentamicin. The lack of enterococcal killing by daptomycin alone in serum and in experimental endocarditis is probably related to the high protein binding of the agent.