meropenem and Hematologic-Neoplasms

Early empiric antibiotic therapy can significantly decrease the risk of mortality and infectious morbidity in patients with hematologic malignancies. Broad-spectrum antibiotics, usually a combination regimen of a beta-lactam and an aminoglycoside, have traditionally been employed against the wide variety of organisms that cause febrile episodes. However, since the 1970's, there has been a shift in epidemiology from Gram-negative to Gram-positive infections, against which traditional combination regimens have only limited efficacy. The carbapenems offer a suitable monotherapeutic alternative as they have a very broad spectrum of antibacterial activity, and equivalent efficacy and safety compared with combination regimes. Trials using imipenem/cilastatin have shown equal efficacy to ceftazidime but neurologic and gastrointestinal toxicity were observed at high doses (1 g 6-hourly). In the largest study to date, meropenem (1 g 8-hourly) provided effective, well tolerated monotherapy for patients with febrile neuropenia, equivalent to a regimen of ceftazidime plus amikacin. It is concluded that meropenem appears to be a realistic option for initial monotherapy in febrile neutropenic patients, providing therapy that is equivalent to a standard regimen of ceftazidime and amikacin.

Topics: Anti-Bacterial Agents; Carbapenems; Drug Therapy, Combination; Fever; Hematologic Neoplasms; Humans; Meropenem; Neutropenia; Randomized Controlled Trials as Topic; Thienamycins

This randomized prospective study was designed to assess whether piperacillin/tazobactam (PIPC/TAZ) is as effective as meropenem (MEPM) as a first-line antibiotic treatment for febrile neutropenia (FN).. FN episodes were randomly assigned to receive either PIPC/TAZ (337.5 mg/kg per day in three doses, 1-hr DIV, maximum 13.5 g per day) or MEPM (120 mg/kg per day in three doses, 1-hr DIV, maximum 3 g per day). Clinical responses were evaluated 120 hr after the DIV.. A total of 434 febrile episodes in 105 patients (42 females and 63 males) with a median age of 8 years (range 0-25) were included in this trial. Blood cultures were positive in 47 out of the 434 episodes (10.8%). Regarding responses to the treatment, success rates between the PIPC/TAZ and MEPM groups were similar (62.4 vs. 65.9%, P = 0.484), even if patients were restricted to those with bacteremia (26.1 vs 37.5%, P = 0.534). Mortality rates did not significantly differ between the two groups (0.8 vs. 0%, P = 0.500).. Both PIPC/TAZ and MEPM appeared to be equally efficacious and safe. Carbapenems are now broadly used to treat FN; however, this may increase the prevalence of drug-resistant bacteria. In this regard, the treatment using PIPC/TAZ for FN is more beneficial.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Female; Hematologic Neoplasms; Humans; Infant; Infant, Newborn; Male; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance.. This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis.. In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods.. We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Ciprofloxacin; Drug Administration Schedule; Female; Fever; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

Many patients with hematologic malignancies show immunosuppression and/or neutropenia, and are at a high risk of developing a serious infection that would require empiric therapy with broad-spectrum antibiotics. However, a thorough comparison of the efficacies of different carbapenems has not been carried out. To compare the efficacies of meropenem (MEPM) and doripenem (DRPM) in febrile patients with hematologic neoplasms, we retrospectively reviewed data of 149 consecutive febrile patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome (MDS) who were treated empirically with MEPM or DRPM. The duration from the start of carbapenem administration to decline of fever was not significantly different between the MEPM and DRPM groups (median, 3 versus 4 days; P = 0.79). Multivariate analysis showed that a diagnosis of MDS and the use of liposomal amphotericin-B or voriconazole are statistically significant risk factors for sustained fever. In conclusion, MEPM and DRPM showed similar efficacies in febrile patients with acute leukemia and MDS.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Female; Fever; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Retrospective Studies; Risk Factors; Thienamycins; Treatment Outcome

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm3) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received i.v. neropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1-30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p = .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group. Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.

Topics: Amikacin; Anti-Bacterial Agents; Drug Therapy, Combination; Fever; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Hematologic Neoplasms; Humans; Infections; Meropenem; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Tazobactam; Thienamycins

Campylobacter bacteremia is an uncommon disease that mainly occurs in immunocompromised patients and is associated with antibiotic resistance, particularly in Campylobacter coli. We report a patient with persistent blood infection because of a multidrug-resistant (MDR) C. coli strain over a 3-month period. Through this period monotherapy with meropenem was associated with the development of resistance to it. Improving immunity status and a combined therapy for intestinal decolonization were useful to control persistent C. coli infection in this patient.

Topics: Anti-Bacterial Agents; Bacteremia; Campylobacter coli; Campylobacter Infections; Hematologic Neoplasms; Humans; Meropenem

Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the β-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate β-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed.

Topics: Anti-Bacterial Agents; Bacteremia; Cohort Studies; Hematologic Neoplasms; Humans; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Sepsis

Autologous stem cell transplant (ASCT) is a widely used and safe procedure to treat mostly hematologic diseases. These patients are at risk of infectious complications, which represents a major cause of morbidity and it is the second cause of mortality. This retrospective 12-year analysis of the incidence, type, and severity of infections in 266 consecutive unselected ASCT patients at our institution provides novel information addressing this issue. We included 266 ASCT procedures. Patients included in the 2006-2013 period are referred to as group 1 (ciprofloxacin prophylaxis and ceftazidime-amikacin as empirical antibiotics), and those in the 2013-2017 period are group 2 (levofloxacin prophylaxis and meropenem as empirical antibiotics). The incidence of febrile neutropenia was 72% in group 1 and 86.2% in group 2 (p = 0.004). The majority of infectious episodes were associated with fever of unknown origin: 55% in group 1 and 59% in group 2. Febrile of unknown origin episodes were 82.6% in group 1 and 80% in group 2. Significant differences between both groups were found in age, hypogammaglobulinemia, and advanced disease at ASCT. No differences were found between groups regarding the most common agent documented in positive blood cultures (Gram+ were 66.6% in group 1 and 69% in group 2 (p = 0.68)). Mortality within 100 days of transplant was low, 1.87%. Regardless of the prophylactic regimen used, most patients experience febrile episodes in the ASCT setting, fever of unknown origin is the most common infection complication, and Gram+ agents are prevalent in both groups. Mortality rates were low. According to our results, ASCT is a safe procedure and there is no clear benefit in favor of levofloxacin versus ciprofloxacin prophylaxis. Both anti-infectious approaches are acceptable, yielding similar outcomes.

Topics: Adolescent; Adult; Aged; Amikacin; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ceftazidime; Ciprofloxacin; Febrile Neutropenia; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Incidence; Levofloxacin; Male; Meropenem; Middle Aged; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Transplantation, Autologous; Uruguay; Young Adult

Optimal dosing of antibiotics is critical in immunocompromised patients suspected to have an infection. Data on pharmacokinetics (PK) of meropenem in patients with haematological malignancies are scarce.. To optimize dosing regimens, we aimed to develop a PK population model for meropenem in this population.. Patients aged ≥18 years, hospitalized in the haematology department of our 1500 bed university hospital for a malignant haematological disease and who had received at least one dose of meropenem were eligible. Meropenem was quantified by HPLC. PK were described using a non-linear mixed-effect model and external validation performed on a distinct database. Monte Carlo simulations estimated the PTA, depending on renal function, duration of infusion and MIC. Target for free trough concentration was set at >4× MIC.. Overall, 88 patients (181 samples) were included, 66 patients (75%) were in aplasia and median Modification of Diet in Renal Disease (MDRD) CLCR was 117 mL/min/1.73 m2 (range: 35-359). Initial meropenem dosing regimen ranged from 1 g q8h to 2 g q8h over 30 to 60 min. A one-compartment model with first-order elimination adequately described the data. Only MDRD CLCR was found to be significantly associated with CL. Only continuous infusion achieved a PTA of 100% whatever the MIC and MDRD CLCR. Short duration of infusion (<60 min) failed to reach an acceptable PTA, except for bacteria with MIC < 0.25 mg/L in patients with MDRD CLCR below 90 mL/min/1.73 m2.. In patients with malignant haematological diseases, meropenem should be administered at high dose (6 g/day) and on continuous infusion to reach acceptable trough concentrations.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Hematologic Neoplasms; Humans; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Thienamycins

In Pseudomonas aeruginosa, fluoroquinolone exposure promotes resistance to carbapenems through upregulation of efflux pumps and transcriptional downregulation of the porin OprD. Evidence of this effect among hematologic malignancy (HM) patients or hematopoietic cell transplant (HCT) recipients receiving fluoroquinolone prophylaxis for neutropenia is lacking.. We retrospectively evaluated episodes of P. aeruginosa bloodstream infections in HM patients or HCT recipients over a 7-year period at our institution. We determined the association of fluoroquinolone prophylaxis at the time of infection with meropenem susceptibility of P. aeruginosa breakthrough isolates and risk factors for meropenem nonsusceptibility. Whole-genome sequencing (WGS) and phenotypic assessments of meropenem efflux pump activity were performed on select isolates to determine the mechanisms of meropenem resistance.. We analyzed 55 episodes of P. aeruginosa bacteremia among 51 patients. Breakthrough bacteremia while on fluoroquinolone prophylaxis was associated with nonsusceptibility to meropenem, but not to antipseudomonal β-lactams or aminoglycosides. The receipt of fluoroquinolone prophylaxis was independently predictive of bacteremia with a meropenem-nonsusceptible isolate. All meropenem-nonsusceptible isolates analyzed by WGS contained oprD inactivating mutations, and all meropenem-nonsusceptible isolates tested demonstrated reductions in the meropenem minimum inhibitory concentration in the presence of an efflux pump inhibitor. A phylogenetic analysis based on WGS revealed several clusters of closely related isolates from different patients.. Fluoroquinolone prophylaxis in HM patients and HCT recipients is associated with breakthrough bacteremia with meropenem-nonsusceptible P. aeruginosa strains, likely due to both mutations increasing efflux pump activity and the epidemiology of P. aeruginosa bloodstream infections in our patient population.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Fluoroquinolones; Genome, Bacterial; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Meropenem; Microbial Sensitivity Tests; Mutation; Polymorphism, Single Nucleotide; Pseudomonas aeruginosa; Pseudomonas Infections

Febrile neutropenia (FN) is a serious complication associated with morbidity and mortality. To manage infections in neutropenic patients, it is necessary to administer empirical antibiotic therapy in a timely and efficient manner. We developed an electronic critical pathway system for a computer-stored medical record system (EGMAIN-GX, Fujitsu), which matches FN patients to either: i) the first-line therapy with meropenem (3 g/day) alone, or ii) the second-line therapy with meropenem plus vancomycin (2 g/day). If patients do not respond to the first-line therapy within 72 hours, then they are provided with the second-line therapy. A total of 28 FN events were treated in 14 patients presenting with hematological malignancies. The mean and median neutrophil counts were 42 (0-300)/microl and 0/microl, respectively. The response rates with the first-line and second-line therapies were 57% and 93%, respectively. There were no serious adverse events. Meropenem is a highly effective treatment for FN. Use of an electronic critical pathway system could ensure that neutropenic patients receive this necessary empiric therapy in a timely manner so as to prevent the serious complications associated with FN.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Critical Pathways; Drug Therapy, Combination; Electronic Health Records; Female; Fever; Hematologic Neoplasms; Humans; Liposomes; Male; Meropenem; Middle Aged; Neutropenia; Thienamycins; Treatment Outcome; Vancomycin; Young Adult

The management of acute appendicitis in the febrile neutropenic patient after intensive chemotherapy is controversial. We report our single-center-experience of 5 children diagnosed with appendicitis during febrile neutropenia after chemotherapy for acute leukemia or lymphoma. All patients presented with an isolated appendicitis without signs of overt mucositis or more diffuse enterocolitis. The clinical diagnosis was confirmed by ultrasonography. Perforation with retrocecal abscess was present in 1 patient. Administration of combination antimicrobial regimens including meropenem resulted in complete resolution in all patients. Our observations indicate that acute appendicitis in clinically stable neutropenic cancer patients can be managed conservatively without surgery.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Appendicitis; Child; Female; Hematologic Neoplasms; Humans; Infant; Male; Meropenem; Neutropenia; Thienamycins