cilastatin--imipenem-drug-combination and Fever

Drug fever is a febrile reaction caused by initiation of one drug or varieties of drugs and often disappears after cessation of the drug(s). Clinically, drug fever is frequently induced by antibiotics, anticonvulsants, and antineoplastics. There are few previous reports about drug fever caused by imipenem/cilastatin.. Here, we described a 66-year-old man undergoing the Ivor Lewis esophagectomy for esophageal carcinoma, who developed drug fever. The patient had a high temperature with shivering after administration of imipenem/cilastatin for 7 days. Furthermore, his temperature came down after discontinuing imipenem/cilastatin and receiving steroids. Body temperature increased rapidly 4 hours after intravenous readministration of imipenem/cilastatin and rapidly decreased to normal after discontinuing imipenem/cilastatin and administering steroids.. Thorough history, blood tests, physical examination, and computed tomography (CT) did not reveal any evidence of fever. Drug fever caused by imipenem/cilastatin was considered. We also present a review of relevant literature and provide a point of reference for the clinical diagnosis and therapy of patients with drug fever.

Topics: Aged; Anti-Bacterial Agents; Cilastatin, Imipenem Drug Combination; Esophageal Neoplasms; Esophagectomy; Fever; Humans; Male; Steroids

In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem-cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases.. Febrile neutropenic patients received either imipenem-cilastatin or piperacillin-tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as "success" and improvement with modification of the initial treatment and death was defined as "failure".. Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem-cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group.. Although failure was slightly higher in the imipenem-cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever; Humans; Imipenem; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

A prospective, open label, randomized, multicentre study was conducted, comparing the efficacy and safety of cefepime with that of imipenem-cilastatin for the management of febrile neutropenia in patients with haematological malignancies. Furthermore, the safety of early discontinuation of antibiotic therapy in patients with fever of undetermined origin (FUO) was assessed. A total of 180 patients with 207 febrile episodes were randomized at start of fever (105 episodes for cefepime and 102 episodes for imipenem). The 2 groups were comparable in terms of age, gender, underlying malignancy, prior transplantation, and presence of central venous catheters. All patients were neutropenic at inclusion with median absolute neutrophil count (ANC) 0.1 x 10(9)/l(range 0-1 x 10(9)/l), and ANC < or = 0.1 x 10(9)/l in 77% of included patients. The mean duration of neutropenia, with ANC < 0.5 x 10(9)/l was 6.2 d. Febrile episodes were classified as microbiologically documented infection (47%), FUO (43%), or clinically documented infection (10%). At final evaluation 1-2 weeks after completion of antibiotic therapy, monotherapy success rates were 40% and 51% in the cefepime and imipenem-cilastatin groups respectively (p = 0.33). The 4-week overall mortality rate was 5%. Three (2%) of the cefepime treated patients and 4 (3%) of the imipenem-cilastatin treated patients died as a result of infection. Adverse events directly related to antibiotic treatment were uncommon and did not differ between groups. Early discontinuation of antibiotic therapy in 31 patients with FUO 48 h after defervescence was not associated with an increased rate of fever relapse or mortality compared with a subgroup of 29 patients where therapy was continued.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cefepime; Cephalosporins; Cilastatin; Cilastatin, Imipenem Drug Combination; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Fever; Follow-Up Studies; Hematologic Neoplasms; Humans; Imipenem; Male; Middle Aged; Neutropenia; Probability; Prospective Studies; Risk Assessment; Single-Blind Method; Survival Analysis; Sweden; Treatment Outcome

We aimed at comparing the effectiveness and safety of piperacillin/tazobactam(PIP-TAZ) versus imipenem/cilastin (IMI) administered as empiric monotherapy in patients with febrile neutropenia.. Patients with hematological diseases who were randomly assigned either PIP-TAZor IMI were enrolled in the study. A sequential strategy of antibiotic therapy addition was applied as long as fever persisted or microorganisms were isolated at 72 h. Moreover, if bacteriologically unconfirmed fever persisted after 5-7 days, an antifungal therapy was started. The treatment was considered successful if fever and clinical signs resolved and/or pathogens were cleared without adding further antibiotics at 72 h. Differences between percentages were analyzed using the *2test.. 137 patients were evaluated. The successful response rate of PIP-TAZ after 72 h was similar to IMI (32.2 and 35.2%). The defervescence time was shorter (3.6 and 4.2 days) and the bacterial response more favourable with PIP-TAZ than with IMI, but statistically significant differences were not reached. The overall response in both groups was 91%.18.2% of episodes were bacteriologically confirmed. The most frequent isolated microorganism was Staphylococcus coagulase-negative(48.8%). There was one only case of septic shock, within the IMI group, and the overall mortality of the group was 8.7%. The occurrence of vomiting in the IMI group was significantly higher than in the PIP-TAZ group (39.9 and 5.6%; p < 0.0001).. PIP-TAZ is as effective as IMI and it constitutes a good choice as an initial empiric monotherapy of febrile neutropenia.

Topics: Adolescent; Adult; Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Prompt initiation of empiric antibiotic therapy is the cornerstone in the therapy of chemotherapy-induced neutropenic sepsis in cancer patients. Ceftriaxone plus gentamicin (ceftriaxone/gentamicin) is the most widely used combination of empiric antibiotics in the Department of Medical Oncology, Singapore General Hospital. However, imipenem/cilastatin has been shown to be a practical alternative. To compare the efficacy and cost effectiveness of monotherapy with our usual combination antibiotic therapy, 50 evaluable neutropenic cancer patients admitted for fever were randomised to empiric imipenem/cilastatin or ceftriaxone/gentamicin. Ceftriaxone/gentamicin was started in 24 patients. The initial clinical response rate to ceftriaxone/gentamicin was 62.5% and 84.6% to imipenem/cilastatin (P = 0.075). The average cost of antibiotics per patient started on ceftriaxone/gentamicin including cost of change of antibiotics was S$63 per day of antibiotic use and for imipenem/cilastatin it was S$252 (P < 0.02). In conclusion, although more patients receiving imipenem/cilastatin had an initial clinical response than those receiving ceftriaxone/gentamicin, this difference was not statistically significant. It would appear that imipenem/cilastatin is equivalent to ceftriaxone/gentamicin for the treatment of neutropenic sepsis. However, ceftriaxone/gentamicin was more cost effective.

Topics: Antineoplastic Agents; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; Costs and Cost Analysis; Drug Combinations; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Imipenem; Male; Middle Aged; Neutropenia; Sepsis

One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days). Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy. TMP/SMZ+AMI seems to be a safe and inexpensive "standard" antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ+AMI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Bacterial Infections; Bone Marrow Transplantation; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Hematologic Diseases; Humans; Imipenem; Leukemia; Lymphoma; Male; Middle Aged; Neutropenia; Pneumocystis Infections; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a randomized trial to compare the efficacy of imipenem/cilastatine (IPM/CS) monotherapy with that of a combination of latamoxef (LMOX) and tobramycin (TOB) in the initial management of fever and neutropenia in patients with lung cancer. Leukocytopenic febrile patients (less than 3,000 leukocytes per microliters; temperature greater than 38 degrees C) with lung cancer given induction therapy were randomly assigned to receive intravenous treatment with either 1 g IPM/CS twice daily or 2 g LMOX plus 90 mg TOB twice daily. A total 101 febrile episodes were studied. Fifty-one episodes were treated with IPM/CS and 50 with LMOX+TOB. Fifty-nine of the febrile episodes were bacteriologically confirmed, while an organism could not be isolated despite the presence of obvious clinical infection in the remaining 42. The response rate was 82% with IPM/CS and 80% with combination therapy. This difference was not statistically significant. The response rate regarding gram-negative infections was 10 out of 14 (71%) in the IPM/CS group and seven out of 12 (58%) in the LMOX+TOB group. This difference was also not significant (P = 0.484). The response rate in severely neutropenic patients (neutrophils less than 100/microliters) was low (P = 0.078). Three patients in the IPM/CS group were withdrawn from the study due to skin rash and vomiting. Therapy with IPM/CS monotherapy was as effective as a combination regimen.

Topics: Adult; Aged; Bacterial Infections; Chi-Square Distribution; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Logistic Models; Lung Neoplasms; Male; Middle Aged; Moxalactam; Multivariate Analysis; Neutropenia; Random Allocation; Tobramycin; Treatment Outcome

One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Antineoplastic Agents; Bacteria; Bacterial Infections; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Prospective Studies; Randomized Controlled Trials as Topic

In a prospective, randomized study we compared ceftriaxone (active ingredient of Rocephin) plus amikacin, ceftazidime plus amikacin and imipenem/cilastatin in the empiric therapy of febrile granulocytopenic (less than 500/mm3) patients with cancer or aplastic anemia. Of 27 evaluable episodes, 12 were treated with ceftriaxone plus amikacin, 5 with ceftazidime plus amikacin and 10 with imipenem/cilastatin. 56% were culture-positive. Septicemia was the most frequent site of infection and Escherichia coli was the most frequently isolated organism. The efficacy of the three regimens was comparable. One failure occurring in each treatment group was successfully treated with an alternative antibiotic regimen. A second failure in the first treatment group did not respond to the alternative treatment either. No major adverse effects occurred. This study demonstrates that the three regimens are excellent in the empiric therapy of febrile granulocytopenic patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Ceftazidime; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Male; Middle Aged; Prospective Studies; Random Allocation; Remission Induction

Seventy-eight patients with cancer experienced 88 episodes of fever while neutropenic and were randomly assigned to receive empiric antibiotic therapy with cefoperazone 2 g intravenously every 12 hours and mezlocillin 4 g intravenously every six hours or imipenem/cilastatin 500 mg intravenously over 30 to 60 minutes every six hours. Within 96 hours of starting antibiotic treatment, 24 patients (57 percent) treated with cefoperazone and mezlocillin and 34 patients (74 percent) receiving imipenem/cilastatin became afebrile. One half of the patients in each arm required changes in the antibiotic regimen because of side effects, persistent fever with a site suspicious for infection, resistant organisms, or breakthrough bacteremias. Forty patients (95 percent) receiving cefoperazone and mezlocillin and 43 patients (93 percent) receiving imipenem/cilastatin recovered from the neutropenic episode. Two patients in each regimen group died of their underlying disease. One patient in the imipenem/cilastatin arm died of Pseudomonas aeruginosa sepsis. Although the two regimens are comparable in efficacy, the incidence of side effects favored the cefoperazone and mezlocillin group. No seizures or bleeding were seen in either arm; however, 19 patients (41 percent) receiving imipenem/cilastatin required pretreatment antiemetic drugs for nausea.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Cefoperazone; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Male; Mezlocillin; Neoplasms; Neutropenia; Thienamycins

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

Topics: Adult; Anaplasma ovis; Anaplasmosis; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Bites and Stings; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyprus; DNA, Bacterial; Doxycycline; Drug Combinations; Female; Fever; Genes, Bacterial; Humans; Imipenem; Phylogeny; Ticks

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

The purpose of this retrospective study was to assess cross-hypersensitivity between imipenem/cilastatin and penicillin in patients with reported penicillin allergies. Medical records of febrile neutropenic, penicillin-allergic bone marrow transplant recipients who received imipenem/cilastatin treatment were retrospectively reviewed. The findings of this study indicate the incidence of cross-reactivity between imipenem/cilastatin and penicillin among patients with a history of penicillin allergy may be lower than previously reported.

Topics: Adult; Aged; Bone Marrow Transplantation; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Reactions; Drug Combinations; Drug Hypersensitivity; Fever; Humans; Imipenem; Incidence; Middle Aged; Neutropenia; Penicillins; Retrospective Studies

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Fever; Humans; Imipenem; Neutropenia

Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile neutropenic cancer patients. We noted in a previous study that response to empiric therapy was related more to disease classification (solid tumors vs. leukemia) than to the regimen chosen. In the present study we based empiric monotherapy on the underlying disease in treating 240 episodes of fever and neutropenia in 145 children. Patients with leukemia or Stage III/IV non-Hodgkin's lymphoma (higher risk group) were treated with imipenem-cilastatin, whereas those with solid tumors or Stage I/II non-Hodgkin's lymphoma (lower risk group) received ceftriaxone. The regimens were modified in 15% of lower risk and 45% of higher risk episodes. Overall successful outcomes were obtained in 93.2% of the higher risk (n = 119) and 97.5% of the lower risk (n = 121) episodes. The two groups differed significantly in duration of neutropenia, frequency of positive blood cultures and superinfection and the need for modification of the monotherapy (P < 0.05). Empiric monotherapy based on primary disease appears to be safe and effective for febrile neutropenic children with cancer at our Brazilian institution. Further studies will be needed before these findings can be generalized to patient populations in other settings.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever; Humans; Imipenem; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Neoplasms; Neutropenia