meropenem and Agranulocytosis

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Ceftazidime; Child; Child, Preschool; Drug Therapy, Combination; Fever; Humans; Infant; Meropenem; Middle Aged; Neoplasms; Prospective Studies; Thienamycins

We explored the adverse drug reaction signals of drug-induced neutropenia (DIN) and drug-induced agranulocytosis (DIA) in hospitalized patients and evaluated the novelty of these correlations.. A two-step method was established to identify the relationship between drugs and DIN or DIA using 5-year electronic medical records (EMRs) obtained from 242 000 patients at Qilu Hospital of Shandong University. First, the drugs suspected to induce DIN or DIA were selected. The associations between suspected drugs and DIN or DIA were evaluated by a retrospective cohort study using unconditional logistic regression analysis and multiple linear regression model.. Twelve suspected drugs (vancomycin, meropenem, voriconazole, acyclovir, ganciclovir, fluconazole, oseltamivir, linezolid, compound borax solution, palonosetron, polyene phosphatidylcholine, and sulfamethoxazole) were associated with DIN, and six suspected drugs (vancomycin, voriconazole, acyclovir, ganciclovir, fluconazole, and oseltamivir) were associated with DIA. The multivariate linear regression model revealed that nine drugs (vancomycin, meropenem, voriconazole, ganciclovir, fluconazole, oseltamivir, compound borax solution, palonosetron, and polyene phosphatidylcholine) and four drugs (vancomycin, voriconazole, ganciclovir, and fluconazole) were found to be associated with DIN and DIA, respectively. While logistic regression analysis revealed that palonosetron and ganciclovir were associated with DIN and DIA, respectively.. Palonosetron and ganciclovir were found to be correlated with drug-induced granulocytopenia. The results of this study provide an early warning of drug safety signals for drug-induced granulocytopenia, facilitating a quick and appropriate response for clinicians.

Topics: Acyclovir; Aged; Agranulocytosis; Electronic Health Records; Ganciclovir; Humans; Meropenem; Neutropenia; Palonosetron; Thrombocytopenia; Vancomycin; Voriconazole

Topics: Aged; Agranulocytosis; Antifungal Agents; Drug Hypersensitivity Syndrome; Female; Humans; Meropenem; Pulmonary Aspergillosis; Skin; Voriconazole

Ciprofloxacin is one of the most commonly used antibacterial agents with relatively few side effects. Serious adverse reactions reported with ciprofloxacin are rare with an incidence of 0.6%. Recently we came across two rare adverse effects of ciprofloxacin, viz. toxic epidermal necrolysis and agranulocytosis. To our knowledge, a total of seven cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis. One case of granulocytopenia, four of pancytopenia and fifteen of leucopenia worldwide have been reported. With the use of ciprofloxacin becoming more and more widespread, these two rare but fatal complications of ciprofloxacin should be borne in mind.

Topics: Administration, Oral; Adult; Agranulocytosis; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukopenia; Meropenem; Neutropenia; Risk Factors; Sepsis; Stevens-Johnson Syndrome; Thienamycins

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic. Combinations of beta-lactams plus aminoglycosides have been the standard empiric therapy for febrile granulocytopenic patients, especially those with profound long-lasting granulocytopenia. The advent of new broad-spectrum cephalosporins and carbapenems has favoured the possibility of empiric monotherapy. Meropenem is a parenteral carbapenem antibiotic stable to renal dehydropeptidase-I which has excellent bactericidal activity against almost all clinically significant aerobic and anaerobic organisms. Meropenem hasta an antibacterial spectrum similar to that of imipenem but it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae, Haemophilus influenzae, Proteus spp, Morganella spp and Providencia spp. Recently, the efficacy, safety, and tolerance of meropenem monotherapy for the empirical treatment of fever in granulocytopenic cancer patients have been compared in two large prospective randomized multicenter trials. The Meropenem Study Group compared monotherapy with meropenem versus ceftazidime and the EORTC conducted a comparative study of meropenem monotherapy versus the combination of ceftazidime plus amikacin. In both groups, success rates were similar by type of infection and infection-related mortality was low. Related adverse events were also similar in both groups. These studies confirm that monotherapy with meropenem is as effective as ceftazidime-containing regimens for the empiric treatment of fever in granulocytopenic patients.

Topics: Agranulocytosis; Ceftazidime; Cephalosporins; Fever; Humans; Meropenem; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Thienamycins