meropenem and Fever

Encephalopathy is reported to have affected 250,000 people in the United States over the last decade, with considerable morbidity and mortality. Baclofen, a gamma-aminobutyric acid-B agonist that acts on the central nervous system, is the drug most widely used to treat spasticity. Baclofen overdose is a potentially deadly condition that can cause encephalopathy and can result from multiple etiologies. Renal disease can contribute to baclofen overdose and encephalopathy, and there are currently no dosing recommendations for patient's on baclofen with renal impairment.. We report an unusual case of a man aged 35 years who presented with persistent fevers, seizures, and normal mentation. The patient presented with intrathecal baclofen use and prior exposure to West Nile Virus. He developed acute kidney injury at hospital secondary to vancomycin use, and mental status declined.. This case highlights that patients with baclofen overdose can initially appear to have serious brain injury, however, full patient recovery can occur in <72 hours. This case provides additional insight into the guidelines for the treatment and management for unknown cause encephalopathy. This case also highlights the link between renal disease, baclofen, and encephalopathy through a review of the literature.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Baclofen; Brain Diseases; Electroencephalography; Fever; GABA-B Receptor Agonists; Humans; Infusion Pumps, Implantable; Infusions, Spinal; Male; Meropenem; Paraplegia; Seizures; Spasm; Spinal Cord Injuries; Vancomycin

A 39-year-old previously healthy man was referred to our hospital because of acute onset of fever and consciousness disturbance. Neurological examinations revealed deteriorated consciousness, nuchal rigidity and Kernig's sign. A lumbar puncture yielded clouded fluid with a WBC 1,012/μl (polynuclear cell 96%), 147.3 mg/dl of protein, 44 mg/dl of glucose and Gram positive cocci. At first, he was treated with ceftriaxon and ampicillin. At Day 2, meropenem was added. Streptococcus agalactiae was isolated from blood and cerebrospinal fluid. He responded promptly to antimicrobial therapy, and within 2 days, he became lucid and afebrile. S. agalactiae was sensitive to ceftriaxone, ampicillin and meropenem. After Day 3, he was treated with meropenem only. We diagnosed his condition as S. agalactiae meningitis and was discharged from our hospital at Day 18. Many cases of S. agalactiae meningitis are known to occur in neonates, pregnant women, elderly, and persons with underlying disease such as diabetes, malignant disorders, liver dysfunction. But cases occurring in a previously healthy adult are rare. Neurologists should be aware that S. agalactiae may be cause bacterial meningitis in a previously healthy adults.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Consciousness Disorders; Drug Therapy, Combination; Fever; Humans; Immunocompetence; Male; Meningitis, Bacterial; Meropenem; Streptococcal Infections; Streptococcus agalactiae; Treatment Outcome

Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia.. To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams.. We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned.. Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients.. Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses.. Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile.. Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Fever; Humans; Imipenem; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Thienamycins

Administration of empirical antibiotic therapy is now standard practice in the management of febrile neutropenia, but there has been considerable debate about the selection of an efficacious empirical antimicrobial regimen over the past 2 decades. A variety of approaches, including both monotherapeutic and multidrug regimens, have been demonstrated to be effective, although no one regimen has been proven to be superior to another. Changes in the epidemiology of infectious organisms and the growing emergence of highly drug-resistant strains make it necessary to continually reevaluate the therapeutic options. Fortunately, the number of therapeutic options has also been broadening as new antimicrobial agents, including third-generation cephalosporins and carbapenem antibiotics such as imipenem and meropenem, become available. Optimal management is directed by the findings of a clinical evaluation of the patient as well as an awareness of institutional patterns of infection and susceptibility of likely infecting organisms.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Therapy, Combination; Fever; Humans; Imipenem; Meropenem; Neutropenia; Thienamycins

Monotherapy with ceftazidime, cefepime, imipenem or meropenem for the empiric treatment of febrile neutropenia appears as effective as the combination therapy involving aminoglycosides. However, empiric therapy with a combination of a beta-lactam plus an aminoglycoside is a reasonable decision under circumstances where Gram negative sepsis is very likely. Monotherapy is usually associated with a modest rate of response in infections caused by Gram positive organisms. In about 30% of the patients, a glycopeptide will be added at some point, because the response to the initial therapy is not considered optimal.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Meropenem; Neutropenia; Sepsis; Thienamycins

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

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic as a result of chemotherapy. Treatment is instituted at the first sign of infection and before the identification of the causative pathogen (empiric treatment). For many years, standard empiric treatment has been combination therapy with beta-lactams and aminoglycosides. The advent of new broad spectrum antibiotics, such as ceftazidime, has introduced the possibility of empiric monotherapy. However, ceftazidime has only modest activity against infections due to Gram-positive organisms, which presently account for at least 50% of infections in neutropenic patients, and resistance to ceftazidime in Gram-negative organisms has been documented. Meropenem is a new carbapenem with a broad antibacterial spectrum with greater in vitro activity than ceftazidime against staphylococci, streptococci and many Gram-negative bacteria. A comparative study of intravenous meropenem (1 g 8-hourly) and ceftazidime (2 g 8-hourly) in the empiric treatment of febrile neutropenic patients with haematological malignancies has been conducted. In an open, randomised trial of the treatment of 338 febrile episodes, all patients survived to 72 hours on both treatments, and meropenem was found to be at least as clinically effective as ceftazidime in eradicating both Gram-positive and Gram-negative infections. Early modification of treatment (48-72 hours) was required for approximately 40% of patients but occurred less frequently in patients treated with meropenem than with ceftazidime. Tolerability of both treatments was good. Meropenem should be compared with standard combination therapy in a large randomised trial before adopting it as empiric monotherapy for febrile neutropenic patients.

Topics: Bacterial Infections; Ceftazidime; Clinical Trials as Topic; Fever; Humans; Infusions, Intravenous; Meropenem; Neutropenia; Randomized Controlled Trials as Topic; Thienamycins

Febrile neutropenia is often observed in patients with hematologic malignancies, especially in those with acute leukemia. Meropenem has potent and broad antibacterial activity against gram-positive and gram-negative bacteria, and is recommended as first-line empiric therapy for febrile neutropenia. In contrast, the safety and efficacy of doripenem in patients with febrile neutropenia and hematologic malignancies is limited. In this randomized, prospective, cooperative, open-label trial, we compared doripenem (1.0 g every 8 h) to meropenem (1.0 g every 8 h) as first-line empiric antibacterial treatment of febrile neutropenia. To evaluate efficacy and safety, 133 hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed febrile neutropenia during or after chemotherapy, were randomized to each drug. Resolution of fever within 3 to 5 days without treatment modification (i.e., the primary endpoint) did not significantly differ between the doripenem and meropenem groups (60.0% vs. 45.6%, respectively; P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the doripenem group than in the meropenem group (78.4% vs. 60.2%, respectively; P = 0.037). Similar rates of adverse events (grades 1-2) were observed in both groups. Thus, we conclude that both drugs are safe and well-tolerated for the treatment of febrile neutropenia in patients with acute leukemia or high-risk myelodysplastic syndrome, and that the clinical efficacy of doripenem is noninferior to that of meropenem. UMIN Clinical Trial Registry number: 000006124.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Chemotherapy-Induced Febrile Neutropenia; Doripenem; Female; Fever; Humans; Leukemia; Male; Meropenem; Middle Aged; Myelodysplastic Syndromes; Prospective Studies

The aim of this study was to evaluate the usefulness of carbapenems as initial treatment for febrile neutropenia (FN), and in patients unresponsive to this initial therapy, to evaluate the efficacy of subsequent treatment with aminoglycosides (AGs) or ciprofloxacin (CPFX). FN patients were randomized to receive cefepime (CFPM, control), panipenem/betamiprom (PAPM/BP), or meropenem (MEPM). Defervescence, an outcome endpoint, was evaluated 3 days later. Patients with minimal response were given CPFX or AGs, and their responses were reevaluated on day 7. A total of 255 patients were included. The efficacies of CFPM, PAPM/BP, and MEPM were comparable. In patients unresponsive to this initial therapy, the efficacy of subsequent CPFX and AGs treatments was also similar. There was no significant between-arm difference in cumulative efficacy on days 14 and 30. Adverse reactions were infrequent and mild. In conclusion, PAPM/BP and MEPM are as useful as CFPM as initial therapy for FN, and AGs are as efficacious as CPFX in patients unresponsive to the initial therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Female; Fever; Hematologic Diseases; Humans; Male; Meropenem; Neutropenia; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

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

Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40 mg/kg for some of the pediatric patients) t.i.d. was administered every 8hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment. The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0% (40/100) in adult and 66.7% (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (> or = 500/mm3) but also in those with lower counts (< 100/mm3), and the efficacy rate was comparable between the two groups: 38.2% in the < 100/mm3 group and 29.4 to 55.6% in the > or = 500/mm3 group. The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100% (8/8 and 4/4, respectively). The time above minimal inhibitory concentration (% T > MIC) in the treatment interval was greater than 90% in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified. The incidence of adverse events was 93.1% in adult and 83.3% in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5% and 66.7%, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include 'chest discomfort', 'blood uric acid decreased', 'lymphocyte deformation', 'blood uric acid increased', 'abnormal funduscopy', 'hypesthesia' and 'hemorrhagic cystitis'. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported. The results show that monotherapy of MEPM 1 g (or 40 mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and wa

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Fever; Humans; Male; Meropenem; Middle Aged; Neutropenia; Thienamycins

The objectives of this study were to develop a population pharmacokinetic (PK) model of meropenem, to simulate the percent time above minimum inhibitory concentration (%T > MIC) at various MICs, and to estimate effective dosage regimens by calculating the target attainment rates against various strains of bacteria. A total of 209 plasma samples (1-3 concentrations per patient) were obtained from 98 adult Japanese patients with febrile neutropenia in an open-labeled Phase 3 study. The final population PK model was fit to a two-compartment model with zero-order input. Creatinine clearance had a positive significant correlation with CL. Gender had a significant effect on Vc; however, this effect was small, and the PK profile in male patients was similar to that in female patients. The population PK parameters developed in this study are useful in simulating PK profiles of meropenem at various dosage regimens precisely for calculation of %T > MIC. The PK-PD analysis indicated that 0.5 g every 6 h (q6h) was more effective than 1 g q12h, although provided 2 g per day in total. A meropenem dosage regimen of 1 g q8h and/or longer infusion duration was better against a pathogen of comparatively low sensitivity, Pseudomonas aeruginosa (for MIC ≥2 μg/ml). Although causative bacteria were identified in a small number of patients, the target attainment rates at 75%T > MIC (89%) were comparable to microbiological response (89%). The present PK-PD analyses under various conditions are useful in the treatment of febrile neutropenia.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteria; Computer Simulation; Female; Fever; Humans; Japan; Kidney Function Tests; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Monte Carlo Method; Neutropenia; Thienamycins

The current management of acute cholangitis consists of antibiotic therapy in combination with biliary drainage. However, the optimal duration of antibiotic therapy after the resolution of clinical symptoms by biliary drainage is unclear. We aimed to evaluate whether discontinuing antibiotic therapy for acute cholangitis immediately after the resolution of clinical symptoms, achieved by endoscopic biliary drainage, was safe and effective.. This prospective study included patients with moderate and severe acute cholangitis. Cefmetazole sodium and meropenem hydrate were used as initial antibiotic therapy for patients with moderate and severe acute cholangitis, respectively. All patients underwent endoscopic biliary drainage within 24 h of diagnosis. When the body temperature of < 37 ° C was maintained for 24 h, administration of antibiotics was stopped. The primary endpoint was the recurrence of acute cholangitis within 3 days after the withdrawal of antibiotic therapy.. Eighteen patients were subjected to the final analysis. The causes of cholangitis were bile duct stone (n = 17) and bile duct cancer (n = 1). The severity of acute cholangitis was moderate in 14 patients and severe in 4. Body temperature of < 37 ° C was achieved in all patients after a median of 2 days (range 1-6) following endoscopic biliary drainage. Antibiotic therapy was administered for a median duration of 3 days (range 2-7). None of the patients developed recurrent cholangitis within 3 days after the withdrawal of antibiotics.. Fever-based antibiotic therapy for acute cholangitis is safe and effective when resolution of fever is achieved following endoscopic biliary drainage.

Topics: Acute Disease; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefmetazole; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Drainage; Female; Fever; Humans; Male; Meropenem; Middle Aged; Prospective Studies; Recurrence; Severity of Illness Index; Thienamycins; Treatment Outcome

The objective of this study was to compare the safety and efficacy of ceftazidime (2 g every 8 h), piperacillin/tazobactam (4 g/500 mg every 6 h), and meropenem (1 g every 8 h), when combined with amikacin (15 mg/kg once daily), in the empirical treatment of high-risk febrile neutropenic episodes in patients with haematological malignancy.. A prospective, comparative study designed in the haematology unit of a university hospital in Turkey.. A total of 89 febrile episodes in 60 neutropenic patients were treated; 29 febrile episodes in 23 patients with ceftazidime plus amikacin (group 1), 30 episodes in 25 patients with piperacillin/tazobactam plus amikacin (group 2), and 30 episodes in 25 patients with meropenem plus amikacin (group 3). The 3 groups were comparable in terms of age, sex, underlying malignancy, pretherapy neutrophil counts, duration of neutropenia and types of infections. Neutropenia, since the start of fever, persisted for > or =10 days in all of the episodes in the 3 study groups. Nearly all of the episodes were seen in patients with acute leukaemia. In 25.8% (23/89) of the febrile neutropenia episodes, an aetiologic organism was isolated, with gram-negative bacteria being the most commonly isolated. The success without modification rates were 34.5%, 30% and 36.7% for groups 1, 2 and 3, respectively (P >0.05). After modification with a different class of antimicrobial therapy, the response rates increased to 65.5%, 63.3% and 70% for groups 1, 2 and 3, respectively (P >0.05). The mean duration of treatment and the time to defervescence were also comparable in all groups. In all arms, side effects were minimal.. It is concluded that the 3 regimens were equally effective and safe in the empirical treatment of high-risk febrile neutropenic episodes.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Ceftazidime; Drug Therapy, Combination; Female; Fever; Humans; Immunocompromised Host; Male; Meropenem; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Prospective Studies; Risk Assessment; Risk Factors; Tazobactam; Thienamycins

Optimal sampling design with nonparametric population modeling offers the opportunity to determine pharmacokinetic parameters for patients in whom blood sampling is restricted. This approach was compared to a standard individualized modeling method for meropenem pharmacokinetics in febrile neutropenic patients. The population modeling program, nonparametric approach of expectation maximization (NPEM), with a full data set was compared to a sparse data set selected by D-optimal sampling design. The authors demonstrated that the D-optimal sampling strategy, when applied to this clinical population, provided good pharmacokinetic parameter estimates along with their variability. Four individualized and optimally selected sampling time points provided the same parameter estimates as more intensive sampling regimens using traditional and population modeling techniques. The different modeling methods were considerably consistent, except for the estimation of CL(d) with sparse sampling. The findings suggest that D-optimal sparse sampling is a reasonable approach to population pharmacokinetic/pharmacodynamic studies during drug development when limited sampling is necessary.

Topics: Anti-Bacterial Agents; Creatinine; Female; Fever; Humans; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Models, Biological; Neutropenia; Research Design; Thienamycins

We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Drug Therapy, Combination; Female; Fever; Hematopoietic Stem Cell Transplantation; Humans; Male; Meropenem; Middle Aged; Neoplasms; Neutropenia; Opportunistic Infections; Penicillanic Acid; Piperacillin; Prospective Studies; Tazobactam; Thienamycins

In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.

Topics: Acute Disease; Adult; Bacterial Infections; Chronic Disease; Cohort Studies; Female; Fever; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Male; Meropenem; Middle Aged; Pilot Projects; Thienamycins

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Child; Child, Preschool; Empiricism; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Meropenem; Neoplasms; Neutropenia; Therapeutic Equivalency; 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

The purpose of this study was to evaluate the impact of granulocyte-colony stimulating factor (G-CSF) on the therapy for febrile neutropenia (FN). Our patient population differed significantly from those of previous studies as no patients received antimicrobial or CSF prophylaxis before randomization and all were solid tumor patients. When the diagnosis of FN was established, patients were started on intravenous meropenem 1 g every 8 hours and randomly assigned to receive G-CSF (5 microg/kg body weight per day subcutaneously) or not. Twenty-eight patients with 30 FN episodes received G-CSF and 25 patients with 30 FN episodes did not receive G-CSF according to randomization. The time to resolution of fever, recovery of neutrophil count over 1000/mm3, duration of hospitalization, need for erythrocyte and platelet transfusion and mortality rate were similar in both study groups. Side effects of therapy were mild. These results provide preliminary evidence that G-CSF administration, in addition to effective antibiotic therapy as treatment of febrile neutropenic patients with solid tumor, does not help improve infection-related morbidity and mortality.

Topics: Adolescent; Adult; Aged; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Fever; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Meropenem; Middle Aged; Neoplasms; Neutropenia; Probability; Prospective Studies; Reference Values; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Survival Rate; Thienamycins; Treatment Outcome

Meropenem is a promising carbapenem antibiotic as an empirical monotherapy in patients with febrile neutropenia (FN). With the limited data of the therapy in pediatric patients, the authors conducted this study to evaluate the efficacy and safety of meropenem as empirical antibiotic therapy in 30 pediatric cancer patients with FN (mean age = 7.5 years), who were admitted to King Chulalongkorn Memorial Hospital from May 2000 to December 2001. Meropenem 60 mg/kg/day was given intravenously every 8 hours. The efficacy of meropenem was assessed as successful, inconclusive and failure on days 3 and 5 of the therapy and compared to that of other empirical antibiotics used from January 1997 to April 2000. The study showed that six blood culture specimens (20%) grew organisms, half of which were considered to be contaminants, and six urine culture specimens (20%) grew gram negative rod bacteria. On day 3 and 5 of the therapy, the success rate of meropenem was higher than that of comparatives (30.0% vs 17.6% on day 3, 50.0% vs 39.3% on day 5). The use of meropenem appeared safe, with minimal side effects. In conclusion, the present study showed that meropenem was safe and tolerable in children. The efficacy as an empirical monotherapy in pediatric cancer patients with FN was satisfactory, with a failure rate of 23.3 per cent on day 5 of treatment.

Topics: Adolescent; Child; Child, Preschool; Female; Fever; Humans; Male; Meropenem; Neoplasms; Neutropenia; Thienamycins

Fifty-four pediatric cancer patients with a total of 100 febrile neutropenic episodes treated at China Medical College Hospital were randomized to receive meropenem or ceftazidime plus amikacin from January 2001 to April 2002. The characteristics of 76 assessable febrile episodes (39 with meropenem and 37 with ceftazidime plus amikacin) were compared between the 2 groups. The success rate with unmodified therapy was not significantly different between the meropenem group (72%) and the ceftazidime-plus-amikacin group (57%). The incidence of side effects was similar between the 2 groups and these side effects were reversible. Microbiologically documented infection, clinically documented infection, and unexplained fever accounted for 35%, 37%, and 28% of episodes, respectively. The clinical response rates in subgroups of documented infection and unexplained fever did not significantly differ between the 2 treatment groups. Meropenem was significantly more effective than ceftazidime plus amikacin in children at high risks of developing severe infection who had profound neutropenia (absolute neutrophil count [ANC] < 100/mm3), prolonged neutropenia (ANC < 500/mm3 lasting for > 10 days), or clinically deteriorating shock (p=0.045). As an empirical treatment, meropenem seems to be as effective and safe as ceftazidime plus amikacin for febrile episodes in children with cancer and neutropenia. Meropenem is more effective for pediatric cancer patients at the high risk of severe infection.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Ceftazidime; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Diarrhea; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacteria; Gram-Positive Cocci; Hospitals, University; Humans; Infant; Male; Meropenem; Neoplasms; Neutropenia; Taiwan; Thienamycins; Treatment Outcome

This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients.

Topics: Bacterial Infections; Ceftazidime; Cephalosporins; Child; Child, Preschool; Escherichia coli; Female; Fever; Humans; Infant; Infant, Newborn; Klebsiella pneumoniae; Male; Meropenem; Neoplasms; Neutropenia; Prospective Studies; Relapsing Fever; Thienamycins; Time Factors; Treatment Outcome

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

Topics: Adolescent; Adult; Amikacin; Cefepime; Cephalosporins; Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Fever; Humans; Infant; Male; Meropenem; Neoplasms; Netilmicin; Neutropenia; Prospective Studies; Thienamycins; Turkey

A total of 101 cancer patients with 121 febrile neutropenia episodes were randomised to receive empirical treatment with i.v. meropenem (1g/8 h) or ceftazidime (2 g/8 h). After 3 days, 89% of patients were on unmodified therapy in the meropenem group, compared with 83% in the ceftazidime group. Of the evaluable episodes (n = 106), the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime (48% vs 38%, P=0.39). Furthermore, initial success with further infections was observed in 22% of episodes treated with meropenem and in 13% of episodes treated with ceftazidime. Glycopeptides were used as first modification in 28% and 39% of meropenem and ceftazidime recipients, respectively. Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures. No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes. In conclusion, meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Drug Tolerance; Female; Fever; Humans; Male; Meropenem; Middle Aged; Neoplasms; Neutropenia; Thienamycins

To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia.. A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events.. The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ceftazidime; Cephalosporins; Double-Blind Method; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Thienamycins

Eighty three patients with neutropenia and cancer were randomised to receive either 1 g meropenem tds or amikacin 15 mg/kg single dose daily plus ceftazidime 2 g tds. No prophylactic antibiotics were allowed before entry to the trial. Seventy seven patients were available for analysis. Infection was microbiologically or clinically documented in 53 episodes (69%). The overall success rate without adjustment was 49% in monotherapy, 37.5% in the combination group. These rates were increased to 65% and 56%, respectively when secondary infection episodes requiring a different class of chemotherapy were taken into account. Median duration for defervescence was 3 days in successfully treated patients in both groups. Only minor reversible side effects were noted in both treatment arms. Meropenem monotherapy seemed as effective and safe as amikacin plus ceftazidime for the empirical treatment of neutropenic cancer patients with fever.

Topics: Adult; Amikacin; Antibiotic Prophylaxis; Ceftazidime; Drug Therapy, Combination; Female; Fever; Humans; Male; Meropenem; Middle Aged; Neutropenia; Prospective Studies; Thienamycins; Treatment Outcome

Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one patients with hematological malignancies (55%) or solid tumors (45%), neutropenia < 500/microliter, and fever > 38.5 degrees C were randomly assigned to either meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15 mg/kg/day) intravenously. Meropenem (n = 34) and ceftazidime/amikacin (n = 37) were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p > 0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29% versus 25%), whereas all gram-negative bacteremias responded except for one in the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72 h. One patient in each group died of gram-positive sepsis resistant to study medication. No significant side effects occurred in any regimen. This study suggests that meropenem monotherapy might be as effective as combination therapy with ceftazidime and amikacin for the empirical treatment of febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Neutropenia; Thienamycins

In this Swedish multicentre study we compared the efficacy of meropenem with ceftazidime for treatment of febrile neutropenia. 192 patients were randomized and the number of evaluable patients was 92 in the meropenem group and 95 in the ceftazidime group. 40 (43%) patients in the meropenem arm and 49 (52%) in the ceftazidime arm had acute leukaemia. 56 (61%) and 52 (55%) patients respectively had a neutrophil count of < 0.1 x 10(9)/l at randomization and the median duration of neutropenia was 6.5 and 8 d, respectively. Thirty-one (34%) and 28 (29%) patients had a microbiologically defined infection, 14 (15%) and 17 (18%) a clinically defined infection and the remaining 47 (51%) and 50 (53%) had unexplained fever. After 72 h of treatment, 46 (50%) patients in the meropenem arm and 53 (56%) patients in the ceftazidime arm were alive on unmodified monotherapy. 42 (46%) and 47 (49%) of these completed the study on monotherapy alone. Only 2 patients (2%) in each arm had to stop treatment owing to allergic reactions. None of the observed differences were statistically significant and we therefore conclude that meropenem was an effective and safe alternative to ceftazidime for empiric treatment of fever during neutropenia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ceftazidime; Cephalosporins; Female; Fever; Humans; Male; Meropenem; Middle Aged; Neutropenia; Opportunistic Infections; Thienamycins; Treatment Outcome

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

The efficacies of meropenem, a novel carbapenem, and ceftazidime, as empirical therapy of febrile neutropenic patients, were compared in a prospective, randomized clinical trial. One hundred and twelve adult patients were given meropenem 1 g tds iv for 153 episodes of fever, while 109 patients received ceftazidime 2 g tds iv for 151 episodes. All patients survived the first 3 days of therapy and, by the end of the treatment courses, 67 (44%) episodes had responded to meropenem, compared with 62 (41%) to ceftazidime. Eighty (53%) episodes initially treated with ceftazidime and 63 (41%) episodes treated with meropenem were considered to have failed treatment because it was thought necessary to administer additional antibacterial agents; however, modifications were made twice as often because of fever that persisted beyond 2-3 days than because of obvious causes of failure such as persistent infection. Three patients in the ceftazidime group and five in the meropenem group died. Meropenem was well tolerated, with no reports of nausea or toxicity to the central nervous system. Although ceftazidime was shown in the present study to be as effective as meropenem, the broader spectrum of activity of meropenem against Gram-positive cocci suggests that it might be more appropriate as empirical therapy of febrile neutropenic patients who are at high risk of acquiring infections caused by these bacteria.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Ceftazidime; Cephalosporins; Female; Fever; Humans; Leukemia; Leukocyte Count; Male; Meropenem; Middle Aged; Neutropenia; Prospective Studies; Thienamycins; Treatment Failure

Infections caused by Robinsoniella peoriensis, particularly bacteremia, are rare, of which only six cases were reported R. peoriensis bloodstream infections. This case report describes an instance of R. peoriensis bacteremia arising while we treated the patient with piperacillin-tazobactam. We treated an 84-year-old female patient with peritoneal carcinoma and febrile neutropenia using piperacillin-tazobactam. The patient's fever subsided. However, she developed a fever again on the fourth day of treatment with piperacillin-tazobactam. Blood cultures taken at this time were positive for R. peoriensis. We substituted meropenem and vancomycin for piperacillin-tazobactam, after which the patient improved. We administered meropenem and vancomycin for 17 days. There is currently no appropriate established treatment for R. peoriensis. In this case, we isolated R. peoriensis from blood cultures using piperacillin-tazobactam, although it was susceptible to piperacillin-tazobactam in vitro. Therefore, monotherapy with penicillins, especially piperacillin-tazobactam, may not be sufficient for R. peoriensis infections, although it was susceptible in vitro. Carbapenem may be effective in the treatment of R. peoriensis bloodstream infections.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Female; Fever; Humans; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Vancomycin

We report a case of brucellosis-induced severe neutropenia in a 2-year-old girl who presented with a 2-week history of fever. On clinical examination, the patient was febrile with mild aphthous stomatitis. However, her general condition was stable, and systemic examination did not show involvement of any other organ. Laboratory test results revealed severe neutropenia, mild anemia, and an elevated serum C-reactive protein level. Flow cytometry of peripheral blood leukocytes revealed no malignancy, and blood film morphology was unremarkable except for mild microcytosis and hypochromia. Antineutrophil antibody and Coombs test results were negative. We administered intravenous cefuroxime; however, therapy was switched to meropenem plus clarithromycin because fever persisted for 5 days, despite treatment. On the 10th day after admission, Brucella serology tests showed positive results, and trimethoprim-sulfamethoxazole plus rifampicin therapy was prescribed for 8 weeks. The fever defervesced, and the child was discharged in a good state of health. Neutropenia persisted for several months but gradually resolved. Neutropenia, defined as an absolute neutrophil count (ANC) < 1.5 cells × 10 9 /L beyond the first year of life, is a benign transient condition associated with an intercurrent infection (usually viral illnesses or infections) in immunocompetent children. However, severe neutropenia (ANC < 0.5 × 10 9 /L) associated with fever necessitates hospitalization and administration of broad-spectrum antibiotics to avoid the high risk of sepsis, particularly in children. Brucellosis is rarely associated with hematologic abnormalities such as neutropenia. Early diagnosis of hematologic complications of brucellosis is essential for prompt initiation of specific and aggressive treatment.

Topics: Anti-Bacterial Agents; Brucellosis; C-Reactive Protein; Cefuroxime; Child; Child, Preschool; Clarithromycin; Febrile Neutropenia; Female; Fever; Humans; Meropenem; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination

Ectopic pregnancy (EP) is an emergency condition in the gynecologic field. Methotrexate (MTX) is a drug of choice for the medical treatment of EP. Severe adverse events are rare among patients treated with MTX for this condition.. We describe a woman with severe multi-organ involvement experiencing about six days of instability after treatment with just a single-dose MTX for EP. This life-threatening condition is not common with a single dose of MTX. A 30-year-old healthy woman was treated medically with MTX for an EP. Three days later the patient was admitted to the emergency department of our hospital with generalized pustular rashes, alopecia, hyperpigmentation, nausea and vomiting, oral ulcers, and raised Creatinine level. Four days later due to pancytopenia, fever, and loss of consciousness, she was transferred to the intensive care unit and was intubated.. After 38 days of hospitalization, treatment was successful with leucovorin and supportive care and the patient's symptoms and clinical manifestations were regressed.

Topics: Abortifacient Agents, Nonsteroidal; Adult; Alopecia; Anti-Bacterial Agents; Drug Hypersensitivity; Erythropoietin; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Hyperpigmentation; Meropenem; Methotrexate; Pancytopenia; Platelet Transfusion; Pregnancy; Pregnancy, Ectopic; Pseudomonas aeruginosa; Pseudomonas Infections; Unconsciousness

Scrub typhus can present with atypical signs and symptoms such as those of acute kidney injury, gastroenteritis, pneumonitis, and acute respiratory distress syndrome. Meningitis, encephalitis, and hepatic dysfunction have also been reported, particularly in severe cases with multisystem involvement. Scrub typhus has never been reported in the literature to cause urinary tract infections (UTIs) which includes cystitis and pyelonephritis.. A 45-year old male presenting to the outpatient unit with fever, right flank pain, and burning micturition for three days was initially treated for UTI. However, he returned to the hospital on the fourth day of illness with persistent symptoms. He was hospitalized, with intravenous (IV) ceftriaxone. Computerized tomography scan of his abdomen-pelvis showed features of acute pyelonephritis, so his antibiotics were upgraded to meropenem and teicoplanin. Despite this, the patient's condition deteriorated. Laboratory investigations showed multisystem involvement: decreasing platelets, raised creatinine, and deranged liver panel. As Kathmandu was hit by dengue epidemic during the patient's hospitalization, on the seventh day of his illness, blood samples were sent for tropical fever investigation. All tests came out negative except for scrub typhus-IgM antibodies positive on rapid diagnostic test. The patient's symptoms subsided after 48 h of starting doxycycline and he became fully asymptomatic four days later. Fever did not recur even after discontinuing other IV antibiotics, favoring scrub typhus disease rather than systemic bacterial sepsis.. Scrub typhus is an emerging infectious disease of Nepal. Therefore, every unexplained fever cases (irrespective of clinical presentation) should be evaluated for potential Rickettsiosis. Moreover, for cases with acute pyelonephritis, atypical causative agents should be investigated, for example scrub typhus in this case.

Topics: Anti-Bacterial Agents; Ceftriaxone; Communicable Diseases, Emerging; Doxycycline; Fever; Humans; Male; Meropenem; Middle Aged; Nepal; Pyelonephritis; Scrub Typhus; Teicoplanin

Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments.. A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness.. The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options.. Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

Topics: Anti-Bacterial Agents; Cefepime; Cilastatin, Imipenem Drug Combination; Computer Simulation; Cost-Benefit Analysis; Decision Support Techniques; Fever; Health Care Costs; Humans; Meropenem; Neutropenia; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

A 62-year-old man with diabetes mellitus and a two-day history of fever and dyspnea presented at our hospital. He was diagnosed with community-acquired pneumonia (CAP), septic shock, and respiratory failure. Sputum Gram staining revealed Gram-negative coccobacilli. Based on the Gram staining findings and history, Acinetobacter baumannii was considered as one of the causative organisms of his CAP. Consequently, he was successfully treated with the initial administration of meropenem. We suggest that A. baumannii should be considered as one of the possible causative organisms of CAP based on a fulminant clinical course, and the presence of Gram-negative coccobacilli.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteriological Techniques; Community-Acquired Infections; Dyspnea; Fever; Gentian Violet; Humans; Male; Meropenem; Middle Aged; Phenazines; Pneumonia, Bacterial; Respiratory Insufficiency; Shock, Septic; Sputum; Staining and Labeling

Melioidosis is a life-threatening infectious disease that is caused by gram negative bacteria Burkholderia pseudomallei. This bacteria occurs as an environmental saprophyte typically in endemic regions of south-east Asia and northern Australia. Therefore, patients with melioidosis are at high risk of being misdiagnosed and/or under-diagnosed in South Asia.. Here, we report two cases of melioidosis from Nepal. Both of them were diabetic male who presented themselves with fever, multiple abscesses and developed sepsis. They were treated with multiple antimicrobial agents including antitubercular drugs before being correctly diagnosed as melioidosis. Consistent with this, both patients were farmer by occupation and also reported travelling to Malaysia in the past. The diagnosis was made consequent to the isolation of B. pseudomallei from pus samples. Accordingly, they were managed with intravenous meropenem followed by oral doxycycline and cotrimoxazole.. The case reports raise serious concern over the existing unawareness of melioidosis in Nepal. Both of the cases were left undiagnosed for a long time. Therefore, clinicians need to keep a high index of suspicion while encountering similar cases. Especially diabetic-farmers who present with fever and sepsis and do not respond to antibiotics easily may turn out to be yet another case of melioidosis. Ascertaining the travel history and occupational history is of utmost significance. In addition, the microbiologist should be trained to correctly identify B. pseudomallei as it is often confused for other Burkholderia species. The organism responds only to specific antibiotics; therefore, correct and timely diagnosis becomes crucial for better outcomes.

Topics: Abscess; Adult; Anti-Bacterial Agents; Burkholderia pseudomallei; Diabetes Mellitus; Diagnostic Errors; Doxycycline; Fever; Humans; Malaysia; Male; Melioidosis; Meropenem; Middle Aged; Nepal; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a ceftriaxone-resistant

Topics: Abdominal Pain; Adult; Agglutination Tests; Anti-Bacterial Agents; Azithromycin; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ceftriaxone; Denmark; Drug Resistance; Escherichia coli; Female; Fever; Humans; Meropenem; Microbial Sensitivity Tests; Pakistan; Plasmids; Polymerase Chain Reaction; Pregnancy; Salmonella typhi; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Travel; Typhoid Fever; Whole Genome Sequencing

Klebsiella pneumonia (K. pneumonia), primarily a hospital-acquired pathogen, can cause a variety of deep-seated infections with significant morbidities. However, in the current scenario of global rise in antibiotic abuse, unexpected infection could be caused by K. pneumoniae.. A 56-year-old male who presented with intermittent headache and low fever was admitted, he had transsphenoidal surgery for pituitary adenoma 3 years ago. Routine laboratory tests revealed an elevated WBC count of 10.12 × 10/L and C-reactive protein (CRP) 12.9 mg/L. computed tomography (CT) revealed the sellar region with suspicious hemorrhage.. The patient was initially diagnosed with acute residual tumor hemorrhage. But the consequent diagnose of Klebsiella pneumoniae purulent meningitis was made based on the cerebrospinal fluid lab test and cerebrospinal fluid (CSF) and blood culture, and CT scan.. Lumbar puncture examination was made and the antibiotics were adjusted to meropenem and vancomycin according to the antibiotic sensitivity test. But because of the patient's unstable vital signs, his family refuse further lateral ventricular drainage.. The infection was out of control and the patient died of spontaneous breath and heartbeat arrest.. Through this case, we could learn that any clue of suspicious intracranial infection should be carefully considered in the current scenario of global rise in antibiotic abuse. The manifestation of intermittent headache and mild fever could be potential signs of fatal infection, and prompt appropriate measures should be taken timely.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Fatal Outcome; Fever; Headache; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Shock, Septic; Thienamycins; Vancomycin

A case of cervical spinal cord injury and quadriparesis with prolonged fever is being described. Initially, the patient received treatment for well-documented catheter-related bloodstream infection. High spiking fever returned and persisted with no obvious evidence of infection. The usual non-infectious causes too were carefully excluded. QUAD fever or fever due to spinal cord injury itself was considered. The pathogenetic basis of QUAD fever is unclear but could be attributed to autonomic dysfunction and temperature dysregulation. Awareness of this little known condition could help in avoiding unnecessary antimicrobial therapy and in more accurate prognostication. Unlike several previous reported cases that ended fatally, the present case ran a relatively benign course. The spectrum of presentations may therefore be broader than hitherto appreciated.

Topics: Accidental Falls; Anti-Bacterial Agents; Bicycling; Catheter-Related Infections; Catheters, Indwelling; Fever; Humans; Male; Meropenem; Middle Aged; Quadriplegia; Spinal Cord Injuries; Thienamycins; Tracheostomy; Treatment Outcome

Although the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients.. Thirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and β-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined.. Thirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal β-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%.. Mortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients.

Topics: Adolescent; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Fever; Fluoroquinolones; Humans; Male; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Thienamycins

A patient with well-controlled HIV-1 infection presented with fever and rigors, a widespread maculopapular rash, and severe generalised arthralgia. Sepsis of unknown aetiology was diagnosed, and treatment with broad-spectrum antimicrobials commenced. Following initial clinical improvement, a right knee septic arthritis developed. Microscopy and culture of the joint aspirate were negative for organisms but 16S rDNA PCR identified Neisseria meningitidis DNA, subsequently verified as capsular genogroup C, thus confirming a diagnosis of disseminated meningococcal sepsis with secondary septic arthritis.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Arthritis, Infectious; Exanthema; Fever; HIV Infections; Humans; Male; Meningococcal Infections; Meropenem; Middle Aged; Neisseria meningitidis, Serogroup C; Polymerase Chain Reaction; Sepsis; Thienamycins; Treatment Outcome

Various complications are reported with Clostridium difficile infection (CDI), including fulminant CDI. Fulminant CDI is an underappreciated life-threatening condition associated with complications such as toxic megacolon and bowel perforation.. A 79-year-old woman presented to the Emergency Department with altered mental status. She was admitted and conservatively treated for a left thalamic hemorrhage. While hospitalized, she developed watery diarrhea due to Clostridium difficile. Although metronidazole was initiated, she developed altered mental status and septic shock. Abdominal x-ray study and computed tomography revealed a significantly dilatated colon and a massive pneumoperitoneum. She underwent subtotal colectomy with a 14-day course of intravenous meropenem. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case suggests that we must be aware of the complications that CDI may present and adequately consider surgical management because early diagnosis and surgical treatment is critical to reduce the mortality of fulminant CDI.

Topics: Aged; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colectomy; Colon; Consciousness Disorders; Diarrhea; Female; Fever; Hemorrhage; Humans; Intestinal Perforation; Meropenem; Metronidazole; Pneumoperitoneum; Shock, Septic; Thienamycins; Tomography, X-Ray Computed

Thyroid abscess is a very rare clinical condition. It usually occurs in immunocompromised individuals or those with underlying malignancy. We report a case of multiple thyroid abscesses in the patient with Pre B acute lymphoblastic leukaemia which developed secondary to hematogenous spread from pyomyositis of right calf muscle. The patient developed sepsis-associated disseminated intravascular coagulation, which got resolved after thyroidectomy. He became afebrile after surgical intervention. Unfortunately, all the cultures were negative. Since there are few case series and reports, there are no clear guidelines for management of thyroid abscess. We conclude that though rare, thyroid abscess may be the cause of persistent fever in immunocompromised patients.

Topics: Abscess; Adolescent; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Clindamycin; Drainage; Fever; Humans; Male; Meropenem; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Pyomyositis; Sepsis; Teicoplanin; Thienamycins; Thyroid Diseases; Thyroid Gland; Thyroidectomy; Treatment Outcome

A 33-year-old previously healthy man injured his gums and subsequently developed dyspnea and fever. A chest X-ray showed nodules and infiltrates in both lungs, and the patient was initially diagnosed with pneumonia and administered meropenem hydrate, although his symptoms did not improve. A blood culture identified Fusobacterium necrophorum, and thrombophlebitis in the internal jugular vein of the neck was observed on computed tomography and ultrasound scans. We replaced the meropenem with clindamycin, sulbactam/ampicillin and metronidazole, and the patient's symptoms improved.

Topics: Adult; Anti-Bacterial Agents; Clindamycin; Dyspnea; Fever; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Jugular Veins; Lemierre Syndrome; Male; Meropenem; Metronidazole; Periodontitis; Radiography, Thoracic; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome; Wound Infection

An increasingly reported entity, Lemierre's syndrome classically presents with a recent oropharyngeal infection, internal jugular vein thrombosis and the presence of anaerobic organisms such as Fusobacterium necrophorum. The authors report a normally fit and well 17-year-old boy who presented with severe sepsis following a 5-day history of a sore throat, myalgia and neck stiffness requiring intensive care admission. Blood cultures grew F. necrophorum and radiological investigations demonstrated left internal jugular vein, cavernous sinus and sigmoid sinus thrombus, left vertebral artery dissection and thrombus within the left internal carotid artery. Imaging also revealed two areas of acute ischaemia in the brain, consistent with septic emboli, skull base (clival) osteomyelitis and an extensive epidural abscess. The patient improved on meropenem and metronidazole and was warfarinised for his cavernous sinus thrombosis. He has an on-going left-sided hypoglossal (XIIth) nerve palsy.

Topics: Adolescent; Anti-Infective Agents; Anticoagulants; Cranial Fossa, Posterior; Fever; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Hypoglossal Nerve Diseases; Jugular Veins; Lemierre Syndrome; Male; Meropenem; Metronidazole; Osteomyelitis; Pharyngitis; Sepsis; Thienamycins; Treatment Outcome; Warfarin

Chemotherapy of paediatric haematological malignancies can induce infectious complications of the gastrointestinal tract, with predilection of the ileocaecal region. Common causes of right lower abdominal pain in the febrile patient with neutropaenia include acute appendicitis, typhlitis, ileus and intussusception. In this case report, we describe a teenage boy with acute appendicitis presenting with pneumoperitoneum during his course of chemotherapy. The incidence, aetiology, diagnosis, investigations and management of this uncommon presentation in a common disease are discussed. The controversial topic of the management of acute appendicitis in a febrile patient with neutropaenia is also reviewed and discussed.

Topics: Abdominal Pain; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Appendicitis; Child; Diagnosis, Differential; Fever; Humans; Laparoscopy; Laparotomy; Male; Meropenem; Pneumoperitoneum; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thienamycins; Treatment Outcome

Glanders is a zoonotic infection inducing acute forms of the disease (pneumonia, sepsis) in humans and animals under certain conditions, which even with the use of modern chemotherapy have unfavourable prognosis. Insufficient of efficacy of antibiotics with in vitro low MIC for planktonic bacterial suspension of Burkholderia mallei in chemotherapy of acute forms of glanders was due to the capacity of the pathogen for intracellular survival and formation of biofilms. Under such conditions the susceptibility of B. mallei to antibiotics lowered by several orders of magnitude. Chemotherapy of the glanders acute forms in animals usually provided only an increase of the lifespan, while among the survivors there was recorded a high relapse rate. More favourable outcomes were observed with the use of in vitro effective antibiotics in the form of clathrate compounds or especially liposomal forms. In the experiments with golden hamsters the survival rate reached 100% in 1000 Dlm infection even with the treatment onset by meropenem liposomal form 48 hours after the infection. Chemotherapeutics in the liposomal form significantly lowered resistance of B. mallei in both the experiments with a suspension of planktonic organisms and the use of bacteria interned in eukaryotic cells (Tetrahymena pyriformis).

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Burkholderia mallei; Ceftazidime; Cricetinae; Doxycycline; Female; Fever; Glanders; Liposomes; Male; Meropenem; Mesocricetus; Microbial Sensitivity Tests; Survival Rate; Terpenes; Thienamycins

We aimed to compare infection rates for two 3-day antibiotic prophylaxis regimens for transrectal ultrasound-guided prostate biopsy (TRUSgbp) and demonstrate local microbiological trends. In 2008, 558 men and, in 2009, 625 men had TRUSgpb. Regimen 1 (2008) comprised 400 mg Ofloxacin immediately before biopsy and 200 mg 12-hourly for 3 days. Regimen 2 (2009) comprised Ofloxacin 200 mg 12-hourly for 3 days commencing 24 hours before biopsy. 20/558 (3.6%) men had febrile episodes with regimen 1 and 10/625 (1.6%) men with regimen 2 (P = 0.03). E. coli was the most frequently isolated organism. Overall, 7/13 (54%) of positive urine cultures were quinolone resistant and (5/13) 40% were multidrug resistant. Overall, 5/9 (56%) patients with septicaemia were quinolone resistant. All patients were sensitive to Meropenem. There was 1 (0.2%) death with regimen 1. Commencing Ofloxacin 24 hours before TRUSgpb reduced the incidence of febrile episodes significantly. We observed the emergence of quinolone and multidrug-resistant E. coli. Meropenem should be considered for unresolving sepsis.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Biopsy; Cephalosporins; Drug Resistance, Bacterial; Drug Resistance, Multiple; Fever; Humans; Male; Meropenem; Middle Aged; Ofloxacin; Prospective Studies; Prostate; Prostatic Neoplasms; Quinolones; Sepsis; Thienamycins; Treatment Outcome

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Bacterial Infections; Ceftazidime; Drug Resistance, Bacterial; Escherichia coli; Fever; Gram-Positive Bacteria; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Hospitalization; Humans; Israel; Meropenem; Middle Aged; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

Topics: Abdominal Wall; Abscess; Anti-Bacterial Agents; Bangladesh; Blood Glucose; Burkholderia pseudomallei; Chills; Clindamycin; Diagnosis, Differential; Fever; Humans; Male; Melioidosis; Meropenem; Middle Aged; Neck; Neck Pain; Saudi Arabia; Thienamycins; Tomography, X-Ray Computed; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Abscess; Acetamides; Acute Disease; Adult; Anti-Bacterial Agents; Bacterial Toxins; Cellulitis; Drainage; Drug Therapy, Combination; Exotoxins; Fever; Humans; Iraq; Leg; Leukocidins; Linezolid; Magnetic Resonance Imaging; Male; Meropenem; Military Personnel; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We describe melioidosis associated with travel to Nigeria in a woman with diabetes, a major predisposing factor for this infection. With the prevalence of diabetes projected to increase dramatically in many developing countries, the global reach of melioidosis may expand.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Burkholderia pseudomallei; Diabetes Mellitus, Type 2; DNA, Bacterial; Female; Fever; Humans; Melioidosis; Meropenem; Middle Aged; Multilocus Sequence Typing; Nigeria; Phylogeny; Risk Factors; Thienamycins; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Aged, 80 and over; Air Pressure; Anti-Bacterial Agents; Axilla; Equipment Design; Fatal Outcome; Fever; Humans; Laryngeal Masks; Lymph Node Excision; Male; Mediastinitis; Meropenem; Pharynx; Spondylitis, Ankylosing; Subcutaneous Emphysema; Thienamycins

Because of the refractory and recurrent nature of febrile neutropenia (FN), definite diagnosis and early empiric treatment with antibiotics are important for FN patients. With this background, guidelines for FN treatment have been published in Japan and overseas, although a treatment method appropriate for clinical practice in Japan has not yet been established. Therefore, we conducted a survey of actual practice, including trends in prescription of antibiotics for FN, in the hope that it would help establish a definitive treatment for FN in Japan. The survey results confirmed that FN patients under care of hematology departments accounted for the largest proportion, followed by pediatrics (hematology), pulmonary medicine, medical oncology, and respiratory surgery, and the proportions of patients diagnosed with FN and those receiving antibiotics in hematology departments are larger than in other departments. Across all departments, cefepime (CFPM) is most frequently used as the initial treatment of choice, accounting for 35.9% of prescriptions, followed by meropenem (MEPM) (24.3%). These drugs are selected because they exhibit high potency and wide coverage against organisms that are presumed to cause FN, and their costs are covered by insurance, while the existence of insurance coverage is the major determining factor for treatment in Japan. Among second-line drugs, MEPM is most frequently used, accounting for 46.3% of prescriptions. The guidelines are commonly used as the basis for treatment, accounting for 52.0% of all departments, especially the guidelines established by the Japan Febrile Neutropenia Study Group. On the other hand, the percentage of departments that have introduced a hospital protocol and clinical path is only 13.0% in total. To provide appropriate treatment for FN patients, insurance coverage and introduction of a hospital protocol and clinical path based on guidelines and evidence are essential. The current situation, in which these are not implemented, is not desirable. The survey results show that the guidelines need to be revised to more closely reflect the actual situation in Japan and hospital protocols and clinical paths need to be introduced.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Critical Pathways; Evidence-Based Medicine; Fever; Humans; Japan; Meropenem; Neutropenia; Physicians; Practice Guidelines as Topic; Practice Patterns, Physicians'; Surveys and Questionnaires; Thienamycins

Topics: Anti-Bacterial Agents; Back Pain; Cefepime; Cephalosporins; Diagnosis, Differential; Drainage; Epidural Abscess; Fever; Humans; Male; Meropenem; Middle Aged; Myelography; Paresis; Prognosis; Radiography, Abdominal; Shivering; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Time Factors; Tomography, X-Ray Computed

To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem-cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia.. Retrospective, single-center cohort study.. 1250-bed urban academic medical center.. One hundred twenty-seven adults with neutropenic fever who received either imipenem-cilastatin or meropenem; imipenem-cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem.. Of the 127 patients, 40 received imipenem-cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem-cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in-hospital mortality (5% vs 7% vs 7%), and 30-day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively.. The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem-cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.

Topics: Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Dose-Response Relationship, Drug; Drug Combinations; Female; Fever; Hospital Mortality; Humans; Imipenem; Male; Meropenem; Middle Aged; Neutropenia; Retreatment; Seizures; Thienamycins; Time Factors

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Diagnosis, Differential; Drug Therapy, Combination; Female; Fever; Fusobacterium Infections; Fusobacterium necrophorum; Headache; Hip; Humans; Magnetic Resonance Imaging; Meropenem; Thienamycins; Tomography, X-Ray Computed; Vancomycin

Topics: Adult; Anti-Bacterial Agents; Diagnosis, Differential; Escherichia coli; Fasciitis, Necrotizing; Fever; Humans; Male; Meropenem; Pain; Penicillins; Thienamycins

A 15-year-old girl developed a persistent bacteraemia with Klebsiella pneumoniae accompanied by systemic symptoms including high fever and rigors after appendectomy. Extensive laboratory and imaging work-up, including tests for an intra-vascular source of infection, did not reveal the origin of the persistent bacteraemia. The Klebsiella pneumoniae isolates were susceptible to gentamicin and colistin and intermediately susceptible to meropenem. The septicaemia persisted despite the intravenous administration of meropenem 1 g and later 2 g every 8 h in combination with intravenous gentamicin and later colistin. The patient was cured only after the continuous intravenous administration of meropenem of 6 g/d.

Topics: Adolescent; Anti-Bacterial Agents; Appendectomy; Appendicitis; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Postoperative Complications; Sepsis; Thienamycins

Population pharmacokinetic parameters of meropenem in 57 febrile neutropenic patients and minimal inhibitory concentration (MIC) data for clinically isolated Pseudomonas aeruginosa and Escherichia coli were applied to estimate the time above the MIC (T>MIC) using the Monte Carlo simulation method. Mean population clearance (CL) and volume of distribution (V(d)) of meropenem were proportional to creatinine clearance (CL(Cr)) and body weight, respectively: CL (L/h)=9.7 x (CL(Cr)(mL/min)/120); V(d) (L)=14.6 x (body weight (kg)/61). In 1000 simulated patients treated with meropenem 0.5g or 1g every 8h, the proportions of patients who had a T>MIC less than 40% of the dosing interval were 46.3% and 39.5% for P. aeruginosa and 5.8% and 5.6% for E. coli, respectively. The overwhelming resistance of the pathogenic microorganisms, especially P. aeruginosa, in our data compared with that reported in North America suggests the importance of regions or countries as a critical factor for determining the dosage regimen of meropenem in addition to patient characteristics and pharmacokinetics.

Topics: Adult; Anti-Bacterial Agents; Creatinine; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Escherichia coli; Fever; Humans; Korea; Meropenem; Microbial Sensitivity Tests; Models, Biological; Neutropenia; Population; Pseudomonas aeruginosa; Thienamycins

Pharmacodynamic investigations with antimicrobials define the relationship between the infecting organism and achievable drug concentrations with clinical outcome.. To examine this relationship for meropenem in a population of patients who are at high risk of infection-related morbidity and mortality.. The study was a retrospective analysis of a multicenter, randomized, blinded clinical trial. A population-based predictive model was created using data from adults with febrile neutropenia and the nonparametric modeling program, NPEM. Patient age, body weight, and serum creatinine level were covariates in the model used to predict unbound concentrations for each patient. Pathogen susceptibility was estimated using product literature minimum inhibitory concentrations for effectiveness against 50% of microorganisms (MIC50) for specific organisms. The pharmacodynamic index of percent time above MIC (% T>MIC) was analyzed for its association with clinical outcome.. A 2-compartment pharmacokinetic model using patient covariates of body weight and renal function best described the pharmacokinetics of meropenem in febrile neutropenic patients. Sixty patients with confirmed gram-positive or -negative bacteremia were studied. An average of 83% T>MIC was identified for the 42 clinical responders compared with 59% T>MIC for the 18 nonresponders (p = 0.04). An 80% clinical response rate was evident when the % T>MIC for meropenem exceeded 75% of the dosing interval (p = 0.01).. To our knowledge, this is the first published report of a relationship between a pharmacodynamic index and clinical outcome in a febrile neutropenic population. Based on this relationship, dosing with intravenous meropenem 500 mg every 6 hours is predicted to be comparable to the currently recommended 1 g every 8 hours for serious infections. Our model provides further justification for a prospective clinical trial to evaluate a pharmacodynamically targeted meropenem dosing schedule as to its ability to improve clinical outcome in these patients.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Drug Administration Schedule; Female; Fever; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Neutropenia; Retrospective Studies; Thienamycins; Treatment Outcome

The aim of this retrospective study was to evaluate the clinical effectiveness of meropenem in immunocompromised children. Between January 1998 and December 2002 in the hemato-oncological units of our hospital meropenem was used in 87 febrile events diagnosed in 55 patients, and 328 bacterial cultures were evaluated. Microorganisms were detected and identified in 64 of the 328 hemocultures; there was a predominance of gram-positive strains (67%). In 49.4% the infection was documented microbiologically. In 16 additional cases the infection was proven clinically and 32.2% of the episodes were considered to be fever of unknown origin. The success rate of the meropenem therapy-excluding the proven fungal or coagulase-negative Staphylococcus infections--was 72.9% and for the whole cohort 49.4%. The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of neutropenic cancer children.

Topics: Adolescent; Adult; Bacteria; Child; Child, Preschool; Drug Evaluation; Female; Fever; Humans; Immunocompromised Host; Infant; Male; Meropenem; Neutropenia; Opportunistic Infections; Retrospective Studies; Thienamycins; Treatment Outcome

Topics: Bacterial Infections; Cohort Studies; Drug Resistance; Fever; Hematopoietic Stem Cell Transplantation; Humans; Meropenem; Multivariate Analysis; Neutropenia; Odds Ratio; Research Design; Risk Factors; Thienamycins; Transplantation, Homologous; Treatment Outcome

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Child; Child, Preschool; Drug Resistance, Bacterial; Fever; Humans; Infant; Meropenem; Neoplasms; Neutropenia; Prospective Studies; Thienamycins; Vancomycin

Infectious complications are the major causes of morbidity and mortality in children receiving chemotherapy for malignant diseases. Granulocytopenia carries the risk of bacterial infection, and also, if prolonged, of fungal infection. The aim of this study was to evaluate the clinical effectiveness of meropenem in immunocompromised children in association with isolated bacteria from blood cultures and clinical background.. Retrospective study of all febrile episodes when meropenem was used in neutropenic children between January 1998 and December 2002 in the haemato-oncological units of the authors hospital. During the study period meropenem was used in 87 febrile events diagnosed in 55 patients (mean age 10 years 5 months), and 328 bacterial cultures were performed. Blood samples were taken from each patient with granulocytopenia (< 0.5 G/l) and fever (> or = 38 degrees C), prior to the start of any antibiotic therapy. For the microbiological process Bactec 9050 (Becton Dickinson) blood culture systems were used.. Microorganisms were detected and identified in 64 (19.5%) from the 328 hemocultures. There was a predominance of Gram-positive strains, 67% (43/64)--the most common bacteria being coagulase negative Staphylococcus (cnS). From the 87 periods in 43 cases (49.4%) the infection was documented microbiologically. In 16 additional cases the infection was proven clinically (based on the clinical course, laboratory and radiologic results) and 32.2% (28/87) of the febrile neutropenic episodes were considered to be fever of unknown origin. Meropenem was used in a mean dose of 60.8 (30-120) mg/kg/die, for 9.3 (2-24) days. The success rate of the meropenem therapy -excluding the proven fungal (n = 13) or cnS (n = 15) infections-was 72.9%. No severe side effects occurred in any regimens.. The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of feverish neutropenic cancer children.

Topics: Adolescent; Adult; Anti-Infective Agents; Antineoplastic Agents; Bacteremia; Bacterial Infections; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Meropenem; Mycoses; Neoplasms; Neutropenia; Retrospective Studies; Thienamycins; Treatment Outcome

Ceftazidime is commonly used as monotherapy of cancer patients with fever and neutropenia. Concern, however, has been raised regarding potential for drug resistance due to its widespread use. Meropenem is a new carbapenem with more extended antibacterial spectrum including anaerobes. It provides better coverage against gram positives. Hence, it may offer an advantage over ceftazidime.. We prospectively treated 49 patients hospitalized for fever (> 38 degrees C) and neutropenia (ANC < or = 500/cmm) with meropenem. We compared their outcome with 50 patients who consecutively received ceftazidime in the immediate past for the same indication.. Comparison of demographic features between the 2 groups revealed no differences in age, gender, type of neoplasm, number of patients with prior antibiotic use, number of days since chemotherapy, absolute neutrophil count and number of patients previously or already hospitalized. Duration of fever, duration of neutropenia and number of patients with pyrexia of undetermined origin were also similar. Therapeutic outcome was same between the two groups. Eighty four percent of patients receiving meropenem and 79% receiving ceftazidime required no modification of the initially assigned therapeutic regimen. Two patients receiving meropenem died. Toxicity was minimal.. We conclude that meropenem offers no significant advantage over ceftazidime in the management of neutropenic febrile patients.

Topics: Adult; Antineoplastic Agents; Ceftazidime; Cephalosporins; Female; Fever; Humans; Male; Meropenem; Neoplasms; Neutropenia; Prospective Studies; 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