cilastatin--imipenem-drug-combination and Bacterial-Infections

Imipenem cilastatin sodium, as a member of a new generation of β-lactam antibiotics, has a broad spectrum of antibacterial activity and a very wide range of application. Thrombocytopenia has been reported as a rare adverse event in several studies of patients treated with imipenem cilastatin sodium. In this study, we present a case of thrombocytopenia associated with imipenem cilastatin sodium in an older patient. The 78-year-old male patient with pulmonary infection was initiated on anti-infection therapy with imipenem cilastatin sodium. On the 9

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Male; Thienamycins; Thrombocytopenia

Carbapenems are broad-spectrum antibacterial molecules. Imipenem-cilastatin and meropenem are the two main molecules used in French healthcare services.. We aimed to evaluate the relative strengths and weaknesses of these two molecules by considering their pharmacokinetic, pharmacodynamic, microbiological, and clinical properties. We demonstrated that imipenem-cilastatin and meropenem are not alike.. Review of the literature by querying the MEDLINE network.. Imipenem-cilastatin is the first marketed molecule of the carbapenem class. It is more effective against Gram-positive cocci. Its stability does not allow for long infusions and its main adverse effect on the central nervous system limits its use. Meropenem is more effective against Gram-negative bacilli. Its stability and its milder adverse effects distinguish it from imipenem-cilastatin.. Meropenem is preferred for daily use in healthcare services when carbapenems are to be used.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biotransformation; Child; Child, Preschool; Cilastatin, Imipenem Drug Combination; Contraindications, Drug; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Drug Stability; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Liver Failure; Meropenem; Molecular Structure; Organ Specificity; Pregnancy; Pregnancy Complications, Infectious; Protein Binding

Infection in the intensive care unit (ICU) empirically requires broad-spectrum antibiotics. Imipenem/cilastatin, often reserved for more serious hospital-acquired infections, is thought to be associated with a higher risk of seizures than other penicillins and carbapenems. We sought to evaluate the safety of imipenem/cilastatin in the treatment of infections, including meningitis, in neurocritical care patients.. Pertinent literature was identified through MEDLINE (1966-2007) using search terms imipenem, seizure, carbapenem, and meropenem. A review of the literature is presented.. Carbapenem antibiotics remain active against most Gram-positive and Gram-negative organisms, and are often used in critically ill patients. Drug-induced seizures are a rare but serious adverse effect, with carbapenems being one of the most common classes of antibiotics associated with seizures. Seizure rates in patients treated with imipenem/cilastatin and meropenem are similar. One small pediatric study of 21 patients showed a high incidence of seizures and is often cited as the reason imipenem should not be used in meningitis. However, many studies noting seizures with both meropenem and imipenem/cilastatin attribute this to patients with lower body weight, elderly, or those with impaired renal function.. When dosed appropriately, imipenem/cilastatin may be used to treat serious infections in critically ill patients with central nervous system (CNS) disorders or injury with minimal seizure risk. Imipenem/cilastatin safety data is lacking for meningitis and cautious use is warranted.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Care; Drug Combinations; Humans; Imipenem; Nervous System Diseases; Protease Inhibitors

The prototype carbapenem antibacterial agent imipenem has a very broad spectrum of antibacterial activity, encompassing most Gram-negative and Gram-positive aerobes and anaerobes, including most beta-lactamase-producing species. It is coadministered with a renal dehydropeptidase inhibitor, cilastatin, in order to prevent its renal metabolism in clinical use. Extensive clinical experience gained with imipenem/cilastatin has shown it to provide effective monotherapy for septicaemia, neutropenic fever, and intra-abdominal, lower respiratory tract, genitourinary, gynaecological, skin and soft tissues, and bone and joint infections. In these indications, imipenem/cilastatin generally exhibits similar efficacy to broad-spectrum cephalosporins and other carbapenems and is at least equivalent to standard aminoglycoside-based and other combination regimens. Imipenem/cilastatin is generally well tolerated by adults and children, with local injection site events, gastrointestinal disturbances and dermatological reactions being the most common adverse events. Seizures have also been reported, occurring mostly in patients with impaired renal function or CNS pathology, or with excessive dosage. Although it is no longer a unique compound, as newer carbapenems such as meropenem are becoming available, imipenem/cilastatin nevertheless remains an important agent with established efficacy as monotherapy for moderate to severe bacterial infections. Its particular niche is in treating infections known or suspected to be caused by multiresistant pathogens.

Topics: Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem

Imipenem-cilastatin, with its broad spectrum of activity and relative safety, offers an excellent alternative for the treatment of many obstetric and gynecologic infections. In addition, the possibilities for intramuscular administration give clinicians additional treatment options. Because of the relatively high cost of imipenem-cilastatin, it should not be considered "first-line" therapy for most obstetric and gynecologic infections at present. Misuse and overuse of imipenem-cilastatin will result in the further development of resistant organisms, as has already been seen with many other antibiotics, and continued monitoring of susceptibility patterns is necessary.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Microbial; Female; Genital Diseases, Female; Humans; Imipenem; Pregnancy; Pregnancy Complications, Infectious

Imipenem is the broadest-spectrum antibiotic currently available but requires frequent intravenous dosing for efficacy. A recently formulated finely milled preparation can be given intramuscularly in small volumes and demonstrates kinetics favorable for 12-hourly intramuscular administration. The intramuscular imipenem formulation has been proven to be effective for mild to moderate infections of many body sites, as demonstrated by other papers in this symposium. The advantages of intramuscular administration include: less frequent dosing, avoidance of the complications of intravenous administration (phlebitis, bacteremia, fluid overload, nursing time), ability to use the drug in settings where intravenous administration is either undesirable or impossible and, surprising to medical personnel, greater patient satisfaction.

Topics: Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Infusions, Intravenous; Injections, Intramuscular; Male

Topics: Bacterial Infections; Child; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Foot Diseases; Humans; Imipenem; Opportunistic Infections; Thienamycins

Imipenem is a new carbapenem antibiotic that has an extremely broad spectrum of antibacterial activity. It has been used to treat a variety of serious infections and an increasing volume of literature documents its value in infections due to multiresistant bacteria. This article reviews the antibacterial activity, pharmacology, and clinical uses of imipenem.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Humans; Imipenem; Thienamycins

This study aimed to investigate the efficiency of imipenem to prevent infectious complications in predicted severe acute pancreatitis (AP).. Consecutive AP patients were randomized to imipenem 3 × 500 mg intravenously daily or an identical placebo. Exclusion criteria were prior AP, chronic pancreatitis, active malignancy, immune deficiency, active infection, concomitant antibiotic treatment, pregnancy, and patients younger than 18 years. Infectious complications including infected pancreatic necrosis, pneumonia, urinary tract infection, positive blood cultures, sepsis, and other infections were assessed as the primary outcome. Secondary outcomes included mortality, persistent organ failure, systemic inflammatory response syndrome, local complications, serious adverse events, and need for surgical intervention.. Forty-nine patients were randomized to each group. Infectious complications were present in 10 versus 12 of 49 patients (relative risk [RR], 0.833; 95% confidence interval [CI], 0.398-1.747). There were no significant differences in infected pancreatic necrosis (RR, 1.5; 95% CI, 0.262-8.588), pneumonia (RR, 1.5; 95% CI, 0.262-8.588), urinary tract infection (RR, 0.6; 95% CI, 0.152-2.374), positive blood cultures (RR, 0.5; 95% CI, 0.047-5.336), sepsis (RR, 0.333; 95% CI, 0.036-3.095), and other (RR, 1.333; 95% CI, 0.315-5.648). We found no significant differences in secondary outcomes.. Concordantly to available evidence, there is currently no ground to support prophylactic use of antibiotics in predicted severe AP.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pancreatitis; Pneumonia; Prospective Studies; Sepsis; Urinary Tract Infections

Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P < 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Intraabdominal Infections; Male; Middle Aged; Treatment Outcome; Young Adult

We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of intravenous doripenem (DRPM) in patients with biliary tract infection requiring biliary drainage in comparison with imipenem/cilastatin (IPM/CS).. After the initial collection of bile, patients were randomly assigned by the registration system of the Clinical Research Organization to receive intravenous drip infusion of DRPM 0.5 g or IPM/CS 0.5 g three times daily in a randomized, open-label manner.. A total of 127 patients were enrolled in the trial (DRPM 62, IPM/CS 65). The characteristics of the 122 patients evaluated for efficacy were well balanced, except for the percentage of patients previously receiving antimicrobials, which was higher in the DRPM group than in the IPM/CS group. The clinical response rate was not significantly different between the DRPM group (93.1 %, 54/58 patients) and the IPM/CS group (93.8 %, 60/64). Non-inferiority assessment using confidence intervals demonstrated the non-inferiority of DRPM-IPM/CS. The incidence of adverse events, for which a causal relationship with either treatment was not ruled out, was 3.3 % (2/60) in the DRPM group and 3.1 % (2/65) in the IPM/CS group, and none was serious.. The clinical efficacy of DRPM in treating moderate or severe biliary tract infection requiring drainage was comparable to that of IPM/CS. DRPM was associated with no serious adverse events and a low incidence of adverse events. The results of this trial demonstrate that DRPM is a useful therapeutic option for moderate or severe biliary tract infection.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Body Temperature; C-Reactive Protein; Carbapenems; Cholangitis; Cholecystitis, Acute; Cilastatin; Cilastatin, Imipenem Drug Combination; Doripenem; Drug Combinations; Female; Humans; Imipenem; Infusions, Intravenous; Male; Middle Aged; Treatment Outcome; Young Adult

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

In this prospective, randomized, open-label clinical trial, we compared the efficacy and safety of two antibiotic regimens for severe diabetic foot infections (DFI). Sixty-two in-patients with DFI received either piperacillin/tazobactam (Pip-Tazo, n = 30) (4.5 g intravenously every 8h) or imipenem/cilastatin (IMP, n = 32) (0.5 g intravenously every 6h). The mean duration of treatment was 21 days for Pip-Tazo and 24 days for IMP. Twenty-two (73.3%) patients in the Pip-Tazo group and 26 (81.2%) patients in the IMP group had DFI associated with osteomyelitis. Successful clinical response was seen in 14 (46.7%) patients in the Pip-Tazo group and in nine (28.1%) patients in the IMP group [relative risk (RR) 1.6 (95% CI 0.84-3.25), p 0.130]. Two patients in the IMP group and none in the PIP-Tazo group relapsed [RR 2 (0.94-4.24), p 0.058]. Eighty-nine microorganisms were isolated: 38 (43%) Gram-positive and 51(57%) Gram-negative. Among patients with positive culture, 47 (96%) had complete and two (4%) had partial microbiological response. Microbiological response rates were similar in both groups (p 1.000). Amputation was performed in 18 (60%) and 22 (69%) patients in the Pip-Tazo and IMP groups (p 0.739) respectively. Side effects were more common in the Pip-Tazo group (30% vs. 9.4%), but they were generally mild and reversible. In conclusion, although the sample size was small and the results did not reach statistical significance, Pip-Tazo produced a better clinical response rate than IMP in the treatment of severe DFI. There was no significant difference between the treatment groups with respect to microbiological response, relapse and amputation rates.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Diabetic Foot; Drug Combinations; Female; Hospitals, University; Humans; Imipenem; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Recurrence; Time Factors; Treatment Outcome

Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.. In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for /=1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (P < 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005).. Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.. ClinicalTrials.gov NCT00136201.

Topics: Adult; Aged; Anti-Bacterial Agents; Asian People; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Minocycline; Peritonitis; Tigecycline; Treatment Outcome

Biapenem is an injectable carbapenem antibiotic. A clinical study was designed to evaluate its efficacy and safety in the treatment of respiratory and urinary infections compared to imipenem/cilastatin.. A total of 216 patients with respiratory or urinary tract infections were enrolled into this multicenter, open-label, randomized controlled clinical study. Each patient was randomly assigned to either the treatment or control group; 106 patients in each group were included in the ITT analyses. The patients were given biapenem 300 mg or imipenem/cilastatin 500 mg/500 mg two or three times daily, i.v. g.t.t. for 7-14 days according to their conditions.. The cure and effective rates were 67.92 and 88.68% in the biapenem group and 76.02 and 93.40% in the imipenem/cilastatin group, the bacterial eradication rates were 93.83 and 98.82%, and the adverse-event rates were 6.54 and 7.41%, respectively. There were no significant differences between the two groups (p > 0.05).. Biapenem is as effective and well-tolerated as imipenem/cilastatin for the treatment of intermediate and severe bacterial infections.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Hospitals, Teaching; Humans; Imipenem; Male; Middle Aged; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections; Young Adult

To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Double-Blind Method; Drug Combinations; Hospital Mortality; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Pneumonia; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome

Experimental and clinical studies demonstrated that probiotics containing lactobacilli significantly improve the outcome of acute pancreatitis. In a prospective, randomized, double-blinded study the role of "Synbiotic 2000", a new synbiotic composition with high colony forming unit (CFU) was evaluated in the treatment of severe acute pancreatitis.. Patients with severe acute pancreatitis were randomized into two groups. Nasojejunal feeding was commenced within 24 hours after admission in both groups and continued for at least seven days. The first group of patients received four different lactobacilli preparations with 1010 CFU, respectively, and prebiotics containing four bioactive fibers (inulin, beta-glucan, resistant starch and pectin) in addition. Patients in the second (control) group received only prebiotics.. 62 patients with severe acute pancreatitis completed the study. Altogether 8 patients died. Lower incidence of multiorgan failure (MOF), septic complications and mortality were detected in the first group compared to the control, but the differences were not significant statistically. The total incidence of systemic inflammatory response syndrome (SIRS) and MOF were significantly different between the two groups (8 vs. 14; p < 0.05). Furthermore, the number patients recovering with complications were significantly less in the first group receiving modern synbiotic therapy compared to the control (p < 0.05). Finally, lower rate of late (over 48 hours) organ failure was detected in the first versus the control group (3.0% vs. 17.2%).. The results suggest that early nasojejunal feeding with synbiotics may prevent organ dysfunctions in the late phase of severe acute pancreatitis. In addition, the data also indicate that the infection of pancreatic necrosis may be associated with early phase organ failure.

Topics: Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Combined Modality Therapy; Dietary Fiber; Dietary Supplements; Double-Blind Method; Drug Combinations; Enteral Nutrition; Female; Humans; Imipenem; Male; Middle Aged; Multiple Organ Failure; Pancreatitis, Acute Necrotizing; Probiotics; Prospective Studies; Survival Rate; Systemic Inflammatory Response Syndrome; Treatment Outcome

Presumptive antimicrobial therapy is an important aspect of the management of intra-abdominal infections. Together with surgery, antimicrobial combinations are still widely used to achieve the required spectrum of activity. The aim of this study was to evaluate the efficacy of parenteral cefepime + metronidazole vs imipenem-cilastatin for the treatment of intra-abdominal infections in adult patients.. Patients with a clinically confirmed diagnosis of intra-abdominal infection were randomized to one of two treatment regimens: cefepime 2 g iv/12 h plus metronidazole 500 mg/8 h or imipenem-cilastatin 500 mg iv/6 h. The primary measure of clinical response was the decline of pre-treatment signs and symptoms of infection. The duration of follow-up was 30 days. Treatment failure was defined as either a lack of improvement or a worsening of pre-treatment signs and symptoms of infection. Surgical management of the infection was determined by the surgeon-in-charge.. Of the 122 intended-to-treat patients included in the study, 60 patients (33 men) were randomized to cefepime + metronidazole and 61 (27 men) to imipenem-cilastatin. Cefepime + metronidazole treatment was successful in 52 (87%) patients and imipenem-cilastatin in 44 (72%) patients (p = 0.004). Microbiological eradication was established in similar proportions in both groups (cefepime + metronidazole, 43; imipenem-cilastatin, 38).. Further studies are warranted to confirm the better results with the cefepime + metronidazole regimen for the treatment of intra-abdominal infections.

Topics: Abdominal Cavity; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacterial Infections; Cefepime; Cephalosporins; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Hospitals, University; Humans; Imipenem; Male; Metronidazole; Middle Aged

This pooled analysis includes 2 phase 3, double-blind trials designed to evaluate the safety and efficacy of tigecycline, versus that of imipenem-cilastatin, in 1642 adults with complicated intra-abdominal infections. Patients were randomized to receive either tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 h) or imipenem-cilastatin (500/500 mg intravenously every 6 h) for 5-14 days. The primary end point was the clinical response at the test-of-cure visit (12-42 days after therapy) in the co-primary end point microbiologically evaluable and microbiological modified intent-to-treat populations. For the microbiologically evaluable group, clinical cure rates were 86.1% (441/512) for tigecycline, versus 86.2% (442/513) for imipenem-cilastatin (95% confidence interval for the difference, -4.5% to 4.4%; P < .0001 for noninferiority). Clinical cure rates in the microbiological modified intent-to-treat population were 80.2% (506/631) for tigecycline, versus 81.5% (514/631) for imipenem-cilastatin (95% confidence interval for the difference, -5.8% to 3.2%; P < .0001 for noninferiority). Nausea (24.4% tigecycline, 19.0% imipenem-cilastatin [P = .01]), vomiting (19.2% tigecycline, 14.3% imipenem-cilastatin [P = .008]), and diarrhea (13.8% tigecycline, 13.2% imipenem-cilastatin [P = .719]) were the most frequently reported adverse events. This pooled analysis demonstrates that tigecycline was efficacious and well tolerated in the treatment of patients with complicated intra-abdominal infections.

Topics: Adult; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Intestinal Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.. A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations.. A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events.. This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.

Topics: Abdomen; Adult; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; Cholecystitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Diverticulitis; Double-Blind Method; Drug Combinations; Female; Humans; Imipenem; Intestinal Perforation; Male; Middle Aged; Minocycline; Peptic Ulcer Perforation; Peritonitis; Tigecycline

Topics: Adult; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Bone Diseases; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Severity of Illness Index; Soft Tissue Infections

One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy). The following results were obtained. 1. One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation. There were not significant differences between the two groups with respect to the background. 2. The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients. The differences between the two groups were not significant. 3. Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained. 4. Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9% respectively. 5. Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment. The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics. Adverse reactions were uncommon with the monotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Imipenem; Immunocompromised Host; Male; Middle Aged; Opportunistic Infections; Penicillins

The clinical effectiveness of a combination treatment using imipenem/cilastatin sodium (IPM/CS) with G-CSF was studied in neutropenic patients (< 500/mm3) with hematological malignancies and secondary infections. Thirty seven patients were entered in the trial, and 30 patients were eligible. This combination was effective in 20 patients, thus the overall efficacy rate was 66.7 percent. The combination was effective in all 6 cases with septicemia, in 10 case out of 15 cases with fever after chemotherapy (efficacy rate; 66.7%), in 3 out of 8 cases with respiratory infections including 7 cases with pneumonia (efficacy rate; 37.5%), and a case with laryngopharyngitis. According to the order of the administration, the efficacy rates were 60.0% in 5 cases in whom G-CSF treatment was started before IPM/CS, 66.7% in 21 cases given both G-CSF and IPM/CS simultaneously, and 75.0% in 4 cases in whom IPM/CS was started before G-CSF. The difference was statistically not significant on the efficacy rates in the three groups. The efficacy in 18 cases treated with monotherapy on antibiotic was 72.2% and that in 12 cases treated with IPM/CS in combination with other antibiotics was 58.3%, and the difference in the efficacy rates in these two groups was not statistically significant. According to the neutrophil counts before and after the treatment, high response rate (60.0%) was obtained in cases of severe neutropenia (less than 100/mm3). Bacteriological examinations showed that all of bacteria detected as pathogens (10 strains of Gram-positive bacteria and 6 strains of Gram-negative bacteria) were eradicated, though 3 strains were replaced by other pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Imipenem; Immunocompromised Host; Male; Middle Aged; Neutropenia

Meropenem is a new carbapenem antibiotic shown to resist degradation by renal dehydropeptidase I. In a multicenter, open-label, prospective trial, we compared the efficacy and safety of meropenem with imipenem/cilastatin in patients with skin and soft tissue infections. Patients received either 500 mg of meropenem every 8 hours (n = 184) or 500 mg of imipenem/cilastatin every 6 hours (n = 193), by intravenous infusion for an average of 6 to 7 days. Satisfactory clinical responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic response rates were high as well: 94% with meropenem and 91% with imipenem/cilastatin. Between-group differences in satisfactory response rates were not significant (95% confidence interval, -2.29 to 6.93 [clinical]; -2.73 to 10.39 [bacteriologic]). Overall pathogen eradication rates (for aerobes and anaerobes) were slightly higher for meropenem. Elevated liver enzymes were the most frequent adverse events in each treatment group. Meropenem was well tolerated and as effective as imipenem/cilastatin in treatment of hospitalized patients with skin and soft tissue infections.

Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cellulitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Hospitalization; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Skin Diseases, Infectious; Soft Tissue Infections; Thienamycins; Ulcer

In order to compare the clinical and microbiological efficacy and safety of meropenem with imipenem/cilastatin, 249 patients with intra-abdominal infections participated in an open randomised comparative multicentre trial. Seventy-five men and 57 women (mean age 51 years) were enrolled in the meropenem group and 67 men and 50 women (mean age 52 years) in the imipenem/cilastatin group. The patients received either meropenem, 500 mg q 8 h, or imipenem/cilastatin, 500 mg/500 mg q 8 h by intravenous infusion for up to 17 days (mean 5 days). Ninety-seven of 99 patients (98%) receiving meropenem were clinically cured while 86 of 90 patients (96%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 89 of 94 evaluable patients (95%) receiving meropenem and in 78 of 81 evaluable patients (96%) receiving imipenem/cilastatin. There was no significant difference in clinical and microbiological efficacy between the two treatment groups. Adverse reactions were noted in 26 patients receiving meropenem and in 36 patients receiving imipenem/cilastatin. The present study shows that meropenem is effective and well tolerated in the treatment of intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; APACHE; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Thienamycins

Using the envelope method, we allocated 125 patients with infections accompanied by hematopoietic disorders into two groups treated with imipenem/cilastatin sodium (IPM/CS) at a daily dose of 1 g/1 g b.i.d. (group BID) or 0.5 g/0.5 g q.i.d. (group QID), and obtained the following results. 1. In group BID, ANLL was observed in 25 patients; ALL in 6; and NHL in 12. In group QID, ANLL was observed in 27 patients; ALL in 7; and NHL in 13. 2. In group BID, efficacy rates were 54.5% (6/11) in sepsis, 63.0% (17/27) in fever of undetermined origin and 50.0% (4/8) in pneumonia, thus the overall efficacy was 61.8% (34/55). In group QID, efficacy rates were 66.7% (4/6) in sepsis, 76.0% (19/25) in fever of undetermined origin and 35.7% (5/14) in pneumonia, thus the over all was 61.1% (33/54). No significant difference in response rates were observed between the two groups. 3. Bacteriologically, 22 bacterial strains were isolated in group BID and 21 21 strains, in group QID. The eradication rates after treatment with IPM/CS was 100% in group BID and 66.7% in group QID. 4. Side effects were observed in 8 patients in group BID and 3 in group QID. Laboratory examination revealed abnormal values in 9 patients in group BID and 6 in group QID. However, all of the side effects disappeared after the suspension or discontinuation of IPM/CS. The efficacies of IPM/CS therapy for severe infections in patients with hematopoietic disease were similar between 1 g/1 g b.i.d. and 0.5 g/0.5 g q.i.d. groups.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Japan; Leukemia; Lymphoma; Male; Middle Aged

We administered imipenem/cilastatin sodium (IPM/CS) to patients with gynecological infections as initial treatment and evaluated changes in blood interleukin 6 (IL-6) as an infection marker. 1. The subjects consisted of 7 patients with chorioamnionitis, 4 with intrauterine infections, and 1 with subcutaneous abscess. IPM/CS (1-2 g/day) was intravenously drip infused. This therapy was markedly effective in 1 patient and effective in 11; the response rate was 100%. 2. IL-6 generally began to decrease earlier than CRP. Before drug administration, correlations were observed between IL-6 and CRP (r = 0.946) between IL-6 and elastase (r = 0.355), and between elastase and CRP (r = 0.579). During the entire course, correlations were observed between IL-6 and CRP (r = 0.581), between IL-6 and elastase (r = 0.303), and between elastase and CRP (r = 0.776). These results suggest that blood IL-6 reflects early the pathologic state and treatment effects, and is a useful infection marker in gynecological infections.

Topics: Adult; Bacterial Infections; Biomarkers; C-Reactive Protein; Chorioamnionitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Genital Diseases, Female; Humans; Imipenem; Interleukin-6; Middle Aged; Pancreatic Elastase; Pregnancy

We evaluated the effectiveness and safety of imipenem/cilastatin sodium (IPM/CS) in gynecological infections at gynecological departments at multiple institutions in Yamagata Prefecture. The subjects consisted of 64 patients with gynecological infections, 9 with urinary tract infections, and 21 with other infections. IPM/CS was intravenously drip infused at a dose of 1-2 g/day. The overall response rate was 97.9% (92/94); 96.9% (62/64) for gynecological infections, 100% (9/9) for urinary tract infections, and 100% (21/21) for other infections. Bacteriologically the response rate was 97.3% (36/37), and the eradication rate was 97% (32/33). As for subjective and objective side effects, only diarrhea was observed in 1 patient. Clinical laboratory examinations showed no abnormal values. These results suggest the usefulness of IPM/CS for gynecological infections.

Topics: Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Genital Diseases, Female; Humans; Imipenem; Japan; Urinary Tract Infections

In a prospective, randomized, controlled study, clinical and bacteriological efficacy of imipenem/cilastatin (I/C) was compared with a standard combination of aminoglycoside + amoxycillin + clindamycin (C) in patients (pts) with severe intra- and postoperative infections. A total of 84 pts were randomly separated into two groups of 42 pts. Diagnoses were pneumonia n = 21 (14 in I/C group and 7 in C), peritonitis n = 45 (16 in I/C group and 29 in C), septicaemia n = 12 (9 in I/C group and 3 in C), and 7 other infections (3 in I/C group and 4 in C). Doses used were imipenem/cilastatin 1 g q 8 h and amoxycillin 2 g q 8 h plus clindamycin 0.6 g q 6 h, plus netilmicin according to serum concentrations. Success rates were 85.4% (n = 35: 34 cured and one improved) in the I/C group and 83.3% (n = 35: 30 cured and five improved) in the C group. Six pts in group I/C and 7 in group C failed to respond to treatment. One patient in the I/C group was not assessable. 62% of the bacterial isolates were eradicated in the I/C group and 55% in group C. 7% were suppressed in I/C and 5% in C. It is concluded that imipenem/cilastatin is an effective and well-tolerated alternative to antibiotic combinations in severe intra- and post-operative infections. It offers the advantages of fewer drug doses and less renunciation of serum drug concentration monitoring.

Topics: Aminoglycosides; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clindamycin; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Intraoperative Complications; Male; Middle Aged; Postoperative Complications; Prospective Studies

The clinical safety and efficacy of imipenem/cilastatin in the treatment of intra-abdominal infections was compared with the combination of aztreonam and clindamycin in a randomized prospective trial. The severity of illness was determined by means of the Apache II score and a fixed outcome reporting scheme was used. One hundred and four patients were entered into the study, of whom 80 were evaluable. Forty-two patients were treated with imipenem/cilastatin (500 + 500 mg qds) and 38 with aztreonam (600 tds) and clindamycin (1000 mg tds). The study groups were comparable for age and sex. The imipenem/cilastatin group differed from the aztreonam and clindamycin group in having significantly more patients with the diagnosis of acute appendicitis (P < 0.01) and a significantly lower mean Apache score (P < 0.05). The predominate microorganisms isolated in both groups were Escherichia coli and Bacteroides fragilis. Treatment with imipenem/cilastatin proved successful in 71% and failed in 24%, and initial success only was seen in 5%. The numbers in the group treated with aztreonam and clindamycin were 64%, 29% and 7% respectively. Severity of illness, as measured by Apache II score, had no influence on the study outcome. Imipenem/cilastatin as well as the combination of aztreonam and clindamycin were effective in the treatment of abdominal infections and no major adverse reactions were seen.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Aztreonam; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clindamycin; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Premedication; Prospective Studies; Surgical Wound Infection; Treatment Failure

The current multicenter study was conducted at five sites using 86 patients to evaluate the safety and efficacy of piperacillin/tazobactam (4 grams per 500 milligrams every eight hours) compared with imipenem/cilastatin (1 gram every eight hours) in the treatment of patients who were hospitalized with a clinically or bacteriologically confirmed diagnosis of intra-abdominal infection. Forty-seven patients received piperacillin/tazobactam and 39 received imipenem/cilastatin. The favorable response among patients who were clinically evaluable with a valid response in the group treated with piperacillin/tazobactam was 87 percent. In the group treated with imipenem/cilastatin it was 77 percent. Bacteriologic eradication rate among bacteriologically evaluable patients with a valid response in the group treated with piperacillin/tazobactam was 100 percent. In the group treated with imipenem/cilastatin it was 89 percent. The eradication rate of pathogens isolated from patients who were evaluable by biologic factors in the group treated with piperacillin/tazobactam was 100 percent and in the group treated with imipenem/cilastatin treatment, 96 percent. In the group treated with piperacillin/tazobactam the incidence and type of adverse reactions were similar to those seen with piperacillin alone. It is concluded that piperacillin/tazobactam is safe and efficacious in the treatment of patients hospitalized with intraabdominal infections and that tazobactam extends the spectrum of piperacillin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; beta-Lactamase Inhibitors; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Peritoneal Diseases; Piperacillin; Tazobactam; Treatment Outcome

The efficacy and safety of piperacillin plus tazobactam and of imipenem plus cilastatin were compared in an open randomized multicentre study. In the piperacillin/tazobactam group, 40 men and 29 women (mean age 53 years, range 18-92) received 4 g piperacillin with 500 mg tazobactam every 8 h; in the imipenem/cilastatin group 40 men and 25 women (mean age 54 years, range 16-91) received 500 mg imipenem with 500 mg cilastatin, also every 8 h. Antibiotics were administered intravenously for at least three days and for not more than 14 days. Infections were verified by culture of material obtained at laparotomy or by puncture of an abscess before the start of therapy. Fifty of 55 evaluable patients in the piperacillin/tazobactam group (91%) and 40 of 58 evaluable patients in the imipenem/cilastatin group (69%) were clinically cured. Four relapses or failures were recorded in the piperacillin/tazobactam group and 18 in the imipenem/cilastatin group (P < 0.005). Eradication of the microorganisms isolated were similar in both groups. Adverse reactions in both groups were mild and dominated by nausea and diarrhoea. At the dosage used piperacillin/tazobactam was as safe as, and statistically more effective than, imipenem/cilastatin in the treatment of intra-abdominal infections caused by sensitive organisms.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; beta-Lactamase Inhibitors; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Injections, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Tazobactam

In order to compare the clinical and microbiological efficacies and safety of piperacillin plus tazobactam with those of imipenem plus cilastatin, 134 patients with intra-abdominal infections (73 patients with appendicitis) participated in an open randomized comparative multicenter trial. A total of 40 men and 29 women (mean age, 53 years; age range, 18 to 92 years) were enrolled in the piperacillin-tazobactam group and 40 men and 25 women (mean age, 54 years; age range, 16 to 91 years) were enrolled in the imipenem-cilastatin group. The patients received either piperacillin (4 g) and tazobactam (500 mg) every 8 h or imipenem and cilastatin (500 mg each) every 8 h. Both regimens were given by intravenous infusion. A total of 113 patients were clinically evaluable. Of 55 patients who received piperacillin-tazobactam, 50 were clinically cured, while 40 of 58 patients in the imipenem-cilastatin group were clinically cured. The differences were significant (Wilcoxon test; P = 0.005). There were 4 failures or relapses in the piperacillin-tazobactam group and 18 failures or relapses in the imipenem-cilastatin group. The microorganisms isolated were eradicated in similar proportions in the two patient groups. Adverse reactions, mainly gastrointestinal disturbances and nausea, were noted in 13 patients who received piperacillin-tazobactam and in 14 patients who received imipenem-cilastatin. Results of the present study show that piperacillin-tazobactam is effective and safe for the treatment of intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Tazobactam; Treatment Outcome

The efficacy of imipenem-cilastatin was compared with that of tobramycin and metronidazole for the treatment of appendicitis-associated abdominal infections in children in an open, randomized trial. Two hundred eighteen patients between 2.5 and 16.8 years of age hospitalized for appendectomy because of suspected acute appendicitis were allocated to 5 treatment groups. The appendix was perforated in 54 (33.8%) of the 160 cases with appendicitis. All patients responded favorably to treatment. Infection in the wound occurred in 15 of 125 (12.0%) of those without preoperative antibiotic therapy and in 5 of 83 (6.0%) of those given imipenem preoperatively (P = 0.12; 95% confidence interval, -2.2 to 14.2%). C-reactive protein decreased significantly faster in those with perforated appendix treated with imipenem than in those treated with tobramycin and metronidazole (58.2 mg/liter vs. 89.4 mg/liter, P less than 0.05 on the third postoperative day). Imipenem-cilastatin was at least as effective and economically comparable as tobramycin and metronidazole for the treatment of appendicitis-associated infections in children.

Topics: Adolescent; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Infant; Male; Metronidazole; Tobramycin

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 and two patients were enrolled in an open-label evaluation of intramuscular imipenem/cilastatin using doses of either 500 or 750 mg every 12 h in the treatment of mild to moderately severe skin and soft tissue infections. Seventy-four of 102 patients were clinically evaluable. Thirty-one patients had abscesses, 20 had cellulitis and 23 had wound infections. One hundred seventy-eight isolates were recovered from these 74 patients (average 2.4 isolates/patient). Sixty of 74 evaluable patients (82%) were cured; 12 of 74 (16%) were improved. Two patients failed to improve. Therapy was well tolerated. Adverse effects occurred in 8 patients. All of these effects were minor, and none required discontinuation of therapy. Eighty-two percent of patients reported no pain with injections. Therapy did not need to be interrupted or discontinued in the remaining 18% of patients reporting moderate local pain with injections. Peak and trough serum imipenem levels were measured in 15 patients receiving a 500-mg intramuscular dose of imipenem/cilastatin. The mean peak imipenem concentration in 15 patients was 10.7 micrograms/ml (range 3.3-17.8); the mean trough concentration was 2.1 micrograms/ml (range 0.8-4.9). The trough levels were higher than those found in healthy volunteers and may reflect the age and mild renal dysfunction in this group of treated patients. Imipenem/cilastatin used for mild or moderate skin and soft tissue infections was both efficacious and well tolerated. Intramuscular therapy with this agent offers advantages over intravenous therapy because of its long apparent half-life and pharmacokinetics.

Topics: Abscess; Bacterial Infections; Cellulitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Injections, Intramuscular; Skin Diseases, Infectious; Wound Infection

Multicenter noncomparative trials of intramuscular administration of imipenem/cilastatin for the treatment of a variety of infections requiring multiple-dose therapy are reviewed. Fourteen centers in the United States and 18 centers elsewhere participated in these studies. A total of 686 patients (461 evaluable) were treated worldwide. The severity of the infection was rated as moderate in 58.9%, mild in 37.2% and severe in 0.6%. The most common sites of infection were the skin and soft tissue (36.2%) and intra-abdominal (17.6%). Polymicrobial infections were relatively common (27%). Dosing regimens in evaluable patients were 500 mg every 12 h (45.1%), 750 mg every 12 h (36.2%) and 500 mg every 8 h (18.6%). The overall clinical outcome was favorable (clinical cure or improvement) for 95% or more of the evaluable patients with the various body system infections, except in gynecologic infections where 89% of the evaluable patients had a favorable outcome and for sepsis where the favorable outcome was 76%. Where data were available for analysis (skin and soft tissue infections) there was no difference in favorable clinical outcome among patients with moderate infection treated with 1.0 g/day (95% favorable) compared with 1.5 g/day (94% favorable). The overall bacteriologic eradication rate was 91%. Clinical adverse effects were similar in type but less common in frequency than those noted in other studies with the intravenous formulation, with nausea, vomiting and diarrhea being most common; no instances of seizures or confusion were observed. The laboratory adverse effects were similar to those seen in other studies with the intravenous formulation, with increased liver enzyme values the most common. The intramuscular injection was well tolerated in 87% of the patients and moderately well tolerated in 6.6%. The efficacy and low incidence of side effects of the intramuscular formulation of imipenem/cilastatin are significant advantages in the cost-effective treatment of infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Injections, Intramuscular; Male; Middle Aged; Pelvic Inflammatory Disease; Respiratory Tract Infections; Skin Diseases, Infectious; United States; Urinary Tract Infections

Fifty-two patients with moderate or severe infections associated with internal medicine were treated with imipenem/cilastatin sodium (IPM/CS) and the efficacy and the safety of this drug were evaluated. There were 20 patients with pneumonia, 10 with acute exacerbation of chronic respiratory tract infections, 9 with sepsis, 2 with pyothorax, 3 with intraabdominal infection, 2 with urinary tract infection, 1 with pulmonary abscess, 1 with infective endocarditis, 4 with fever of unknown origin. Forty-four patients were evaluable for the efficacy. Clinical efficacies were excellent in 12 patients, good in 26, fair in 3 and poor in 3. The overall clinical efficacy was 86.4%. The efficacy rate was 63.6% in patients previously treated and 93.9% in patients previously untreated with other antibiotics. Bacteriologically, Staphylococcus aureus (8 strains), Streptococcus pneumoniae (5), Streptococcus pyogenes (1), other Gram-positive coccus (1), Klebsiella pneumoniae (8), Haemophilus influenzae (4), Pseudomonas aeruginosa (3), Serratia marcescens (3), Escherichia coli (3), Branhamella catarrhalis (1), Citrobacter freundii (1), Klebsiella oxytoca (1), Enterobacter sp. (1), and Peptostreptococcus sp. (1) were eradicated. P. aeruginosa (3) and Acinetobacter sp. (1) decreased. S. aureus (1), S. epidermidis (1), P. aeruginosa (5), and S. marcescens (1) persisted or appeared. The eradication rate was 83.7%. Six patients showed adverse reactions including general fatigue 1, epigastralgia 1, eruption 1, eosinophilia 1 and elevation of S-GOT 2. But all of the adverse reactions were mild or slight, and transient. These findings indicate that IPM/CS is a useful and safe drug against bacterial infections in internal medicine.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged

Imipenem/cilastatin sodium (IPM/CS), which has a broad spectrum of activity against both Gram-positive and -negative bacteria including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, was used as the second choice for severe infections associated with hematological disorders. Sixty-five patients were treated with IPM/CS. Among them, 53 patients were evaluable for the clinical efficacy. Twelve patients were not evaluable due to the following reasons: 5 patients were treated with combinations of other regimens such as cefzonam, cefmenoxime, ciprofloxacin or gamma-globulin, 5 were patients to whom IPM/CS was administered as the first choice, and the remaining 2 patients were thought to be suffering not from febrile infections but from febrile tumor. Excellent responses were observed in 10 (18.9%) patients and good responses in 23 (43.4%) patients, with an overall rate of efficacy of 62.3%. The efficacy in septic patients was 75% (3/4), and that in patients whose peripheral granulocytes were continuously below 100/microliter was also 75% (6/8). Two patients who suffered from tumor fever and 5 patients who had received no chemotherapy before IPM/CS administration were included in the final evaluation of side effects. Side effects were observed in 16 patients (16/60, 26.7%). In a 61 years, female patient, a skin eruption was found 4 days after IPM/CS therapy was started. In 15 patients, mild gastrointestinal symptoms such as nausea and vomiting were identified within a few days after IPM/CS treatment was started. Abnormal laboratory data such as eosinophilia, liver dysfunction or renal dysfunction were also identified in 4 patients (4/60, 6.7%). Degrees of these abnormalities were very slight, however, and the continuation of treatment was not disturbed. These results indicated that IPM/CS was an effective second line regimen of chemotherapy for the treatment of severe infections in patients with hematological disorders.

Topics: Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Hematologic Diseases; Humans; Imipenem; Infusions, Intravenous; Male; Middle Aged

Imipenem/cilastatin sodium (IPM/CS) was administered to a total of 67 patients with severe infections complicating hematological disorders and solid tumors. Fifty patients are included in the present analysis of efficacy and 64 in that of safety. 1. Out of 31 patients with hematological disorders, responses were excellent in 10 patients, good in 10 patients, and the efficacy rate was 64.5%. Out of 19 patients with solid tumors, responses were excellent in 8 patients, good in 8 patients and the efficacy rate was 84.2%. 2. For patients whose responses to other antibiotics had been poor, the efficacy rate was 59.3% in the group with hematological disorders and 62.5% in the group with solid tumors. 3. The relationship between the neutrophil count and efficacy was studied in the patients with hematological disorders. The efficacy rate for 8 patients whose neutrophil counts were 500/mm3 or less was 75.0%. 4. For the patients with hematological disorders, the efficacy rate for patients from whom causative organisms were isolated was 70.0% and that for patients for whom they were unknown was 61.9%. 5. Adverse reactions were observed in 3 patients and abnormal laboratory test results in 2 patients. However, they were mild and disappeared after discontinuation of this drug. From these results, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections complicating hematological disorders and solid tumors.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Humans; Imipenem; Leukemia; Lymphoma; Male; Middle Aged; Myeloproliferative Disorders; Neoplasms

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Humans; Imipenem; Male; Middle Aged

The safety and efficacy of imipenem/cilastatin were evaluated in 21 children, ages 3 to 48 months, with bacterial meningitis. Eradication of bacteria from the cerebrospinal fluid was demonstrated within 24 hours of antibiotic therapy in all but 2 patients who had Haemophilus influenzae type b meningitis and ultimately achieved bacteriologic cure after 2 to 3 days of imipenem/cilastatin therapy. Cerebrospinal fluid penetrations of imipenem and cilastatin were determined at various times after drug administration with mean cerebrospinal fluid: serum ratios of 14 and 10% for imipenem and cilastatin, respectively. The study was terminated when 7 (33%) patients developed seizure activity after antibiotic therapy was administered. The usefulness of imipenem/cilastatin for the treatment of bacterial meningitis in children may be limited by a possible increased incidence of drug-related seizure activity.

Topics: Anti-Bacterial Agents; Bacterial Infections; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Infant; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Retrospective Studies; Seizures

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

We conducted a prospective randomized clinical trial to compare the efficacy and tolerability of monotherapy with ceftriaxone (active ingredient of Rocephin) (CRO) versus imipenem/cilastatin (I/C) in febrile cancer patients with or without neutropenia. 120 febrile episodes were randomized and 89 (75%) were evaluable for efficacy analysis. The overall response rates to both regimens were good (86 and 79% improved in response to CRO and I/C, respectively). Overall mortality was low and similar in the two groups. Both regimens were well tolerated. Our preliminary data corroborate the efficacy of CRO or I/C as empirical monotherapy for febrile episodes in cancer patients. It will be up to future investigations to show whether one of these regimens is superior to the other.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Neutropenia; Prospective Studies; Random Allocation; Remission Induction

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic of the carbapenem class and its renal dehydropeptidase-I inhibitor in a 1:1 ratio, were performed in neonates, premature infants and an infant. IPM/CS was administered intravenously to 4 neonates and 5 premature infants at a dose level of 10 mg/kg. Plasma levels and urinary excretion of IPM and CS were determined in 2 neonates and 2 premature infants after 30-minute infusion, and in 2 neonates and 3 premature infants after 1-hour infusion. Plasma and cerebrospinal fluid (CSF) concentrations of IPM and CS were determined in 2 cases with purulent meningitis with ages of 2 and 26 days and 1 with purulent meningitis/bacteremia with an age of 4 days. The drug was administered to a total of 31 patients with ages between 0 and 30 days, consisting of neonates, premature infants and an infant (24 suffering with various bacterial infections, 5 treated for prophylaxis of infections and 2 treated for aseptic meningitis diagnosed at the completion of therapy) by intravenous drip infusion in a mean daily dose level of 50.1 mg/kg in 2 to 4 divided doses for 9 days on the average. Clinical efficacy, prophylactic effectiveness and bacteriological response of IPM/CS were evaluated in 29 cases. Adverse effects and abnormal laboratory test results were examined in 31 cases including 2 drop-out cases. The results obtained are summarized as follows. 1. Plasma concentrations of IPM and CS after 30-minute infusion of the drug reached their peaks at the end of administration, and obtained values were 22.4 to 29.0 micrograms/ml for IPM and 26.3 to 34.6 micrograms/ml for CS, thus peak plasma levels of CS were a little higher than IPM. Plasma half-lives of IPM were 1.05 to 2.43 hours, and those of CS were 1.24 to 4.76 hours, and the half-life of CS tended to be longer than that of IPM. Drug concentrations in plasma after 1-hour infusion of IPM/CS reached their peaks at the end of administration and the levels of CS (25.7 to 32.0 micrograms/ml) were a little higher than those of IPM (20.8 to 23.9 micrograms/ml). Plasma half-lives of IPM were 1.40 to 1.63 hours, whereas those of CS were 1.51 to 2.90 hours. The half-life of CS tended to be longer than IPM. 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Drug Combinations; Female; Humans; Imipenem; Infant, Newborn; Infant, Premature, Diseases; Male; Multicenter Studies as Topic

One hundred ninety-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 182 patients in whom efficacies are evaluable, responses were excellent in 50 patients, good in 52, fair in 21 and poor in 59, and the efficacy rating was 56.0%. 2. The efficacy rating in 87 patients who had failed to respond to prior treatment with other antibiotics was 58.6%. 3. There were significant differences in efficacy ratings when patients were grouped according to differences the number of neutrophils after treatment, less than 100, 101 approximately 500 and over 501/mm3. 4. The eradication rate in 38 patients from whom causative organisms were isolated was 75.8%. 5. Out of 197 patients in whom the safety was evaluable, side effects were observed in 19 patients (9.6%) and abnormal laboratory test values in 15 (7.6%).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Drug Combinations; Female; Humans; Imipenem; Infusions, Intravenous; Leukemia, Myeloid, Acute; Leukocyte Count; Lymphoma; Male; Middle Aged

Imipenem-cilastatin was evaluated for tolerability and efficacy in a multicenter open, noncomparative trial involving 178 infants and children with bacterial infections. Imipenemcilastatin was administered in total daily dosages of 100 mg/kg for patients up to 3 years of age and 60 mg/kg for those more than 3 years of age. Favorable clinical response was achieved in 98 of 100 patients judged evaluable for efficacy. Adverse effects were generally mild and reversible and included diarrhea alone or with vomiting (5.1%), irritation of intravenous infusion site (3.3%) and rash (2.2%). Changes in laboratory test values reported most frequently were thrombocytosis (8.9%), elevations in aspartate aminotransferase (7.9%) and alanine aminotransferase (5.6%) and eosinophilia (8.4%). This safety profile appears to be comparable to that of other beta-lactam antibiotics. Moreover imipenem-cilastatin was effective in infections caused by a broad spectrum of pathogens that include Haemophilus influenzae, Staphylococcus aureus, P. aeruginosa and anaerobes. These attributes suggest that imipenem-cilastatin should be safe and effective in selected pediatric patients.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Imipenem; Infant; Infant, Newborn; Male; Multicenter Studies as Topic; Prospective Studies; United States

The comparative efficacy of imipenem-cilastatin versus clindamycin and gentamicin in the treatment of polymicrobial infections was evaluated. Eleven patients completed treatment with the former and nine with the latter. Conditions treated included infected extremity ulcers, peritonitis, perirectal abscess, soft-tissue abscess, abdominal abscess, and acute diverticulitis. Similar rates of bacteriologic and clinical cure or improvement were achieved with the two treatments. Superinfection occurred in two patients who received imipenem-cilastatin and one who received clindamycin and gentamicin. No significant difference in adverse effects was noted. Imipenem-cilastatin appears to be an effective antibiotic in treating polymicrobial infections; however, a much larger patient population would be required to detect a significant difference in the efficacy rates or frequency of adverse effects when comparing the two regimens.

Topics: Adult; Aged; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clindamycin; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Gentamicins; Humans; Imipenem; Male; Middle Aged; Random Allocation

Surgical infection remains a leading cause of hospital morbidity and mortality. We compared the efficacy and toxicity of imipenem-cilastatin sodium in 32 patients with that of clindamycin phosphate and gentamicin sulfate in 25 patients. In the imipenem-cilastatin group, 87.5% had a favorable outcome, with a 12.5% failure rate and 13 adverse reactions. In the clindamycin-gentamicin group, 80% had a favorable outcome, with a 20% failure rate and ten adverse reactions. Two significant superinfections with Pseudomonas and Candida were noted in patients treated with impenem-cilastatin. Each group had one case of Clostridium difficile-associated colitis. Cost analysis showed no differences between treatment arms, except in the appendicitis subgroup. For serious surgical infections, single-agent therapy with imipenem-cilastatin appears to be as efficacious as combination therapy with clindamycin and gentamicin.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clindamycin; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Female; Gentamicins; Humans; Imipenem; Male; Middle Aged; Prospective Studies; Random Allocation; Thienamycins

Observations on 1,754 patients treated with imipenem/cilastatin in phase III dose-ranging studies in the United States were reviewed to determine risk factors for seizures. The patients were moderately to severely ill with numerous background disorders known to be associated with an increased risk of seizures. Fifty-two patients (3 percent) had seizures and in 16 (0.9 percent) of them the seizures were judged by the investigators to be possibly, probably, or definitely related to imipenem/cilastatin. An incidence of seizure of 2 to 3 percent was noted among patients treated with other antibiotics (usually including a beta-lactam in the regimen) at times when imipenem/cilastatin was not being given. The average time of onset of seizures for patients receiving imipenem/cilastatin was seven days after start of therapy. As with other beta-lactam antibiotics, central nervous system lesions and disorders including seizures and renal insufficiency were found to be strong risk factors for seizures. Imipenem/cilastatin dosages in excess of those currently recommended by the manufacturer, particularly in patients with renal insufficiency, were also associated with an increased risk of seizures. There was an association with Pseudomonas aeruginosa infection that remained statistically significant even after controlling for imipenem/cilastatin dosage as well as for the other factors indicated. A high background incidence of seizures in general in a group of severely ill patients makes it both difficult to assess the etiology of a seizure and important to consider the risk factors when choosing the appropriate dose of an antibiotic. Guidelines are presented for appropriate dosing of imipenem/cilastatin in relation to renal function, body weight, and infecting pathogen.

Topics: Anti-Bacterial Agents; Bacterial Infections; Body Weight; Central Nervous System Diseases; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Kidney Function Tests; Male; Regression Analysis; Retrospective Studies; Risk Factors; Seizures; Thienamycins; Time Factors; United States

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

In a randomised and coordinated multicentre study, 143 patients with severe infections received treatment with either imipenem/cilastatin (72; I/C group) or cefotaxime combined with metronidazole and optional cloxacillin (71; CX/M/CL group). 67 patients in the I/C group and 65 in the CX/M/CL group were evaluable for clinical efficacy. 35 (I/C) and 44 (CX/M/CL) patients had bacteriologically documented infections. The clinical cure rate was 91% for I/C and 94% for CX/M/CL, and the bacteriological efficacy (eradicated strains) was 86% and 81%, respectively. Local reactions (phlebitis) were frequent in each group (I/C 18% and CX/M/CL 25%). Clinical side effects other than phlebitis (I/C 17% vs. CX/M/CL 13%) were mostly mild. Diarrhoea did not occur in I/C group. Laboratory untoward effects were mild and infrequent in each group. Reinfections of the urinary tract and superinfections at all sites prevailed in the CX/M/CL group (9 vs. 6 and 6 vs. 2, respectively). The superinfections were mostly mild. The efficacy and safety of I/C in severe infections were comparable to those of CX/M/CL.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cloxacillin; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Metronidazole; Random Allocation; Thienamycins

In a prospective, controlled and randomized study, the clinical and bacteriological efficacy of imipenem/cilastatin was compared to that of a standard combination of an aminoglycoside (tobramycin or netilmicin), amoxicillin and clindamycin in patients with life-threatening postoperative infections. Doses used were imipenem/cilastatin 1 g q 8 h, amoxicillin 2 g q 8 h and clindamycin 0.6 g q 6 h. Aminoglycoside doses were individual and monitored six times weekly with serum concentration assays. Thirty-eight patients were entered into the study; 19 in each group. Diagnoses were pneumonia (five in the imipenem/cilastatin group and four in the combination group), peritonitis (eight in the imipenem/cilastatin and 13 in the combination group) and septicemia (five in the imipenem/cilastatin and two in the combination group). The two groups were comparable with respect to sex, age, underlying diseases and duration of antibiotic therapy. In the imipenem/cilastatin group, 14 patients were cured and one improved (79%). In the combination group, 11 were cured and 5 improved (74%). Four patients in the imipenem/cilastatin and five in the combination group failed to respond to treatment. In the former group 77% of the bacterial isolates were eradicated and 15% were suppressed. Corresponding frequencies in the combination group were 67% and 22%, respectively. Persistence of isolated pathogens was seen in 8% and 11%, respectively. It is concluded that imipenem/cilastatin seems to be an effective and well tolerated alternative to antibiotic combinations in the treatment of life-threatening postoperative infections. It also offers the advantages of fever antibiotic doses and renunciation of aminoglycoside serum concentration monitoring.

Topics: Adult; Aminoglycosides; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clindamycin; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Postoperative Complications; Prospective Studies; Random Allocation; Thienamycins

The clinical efficacy and safety of imipenem/cilastatin in the empirical treatment of adult non-immunocompromised patients with severe bacterial septicemia was studied in a prospective and open trial. The dosage of imipenem/cilastatin was 500 mg q 6 h. Of 58 patients included, 41 were evaluable for efficacy. In those patients, 35 had chronic underlying diseases and the foci of bacteremia were identified in 37; the most common ones being cardiovascular, urologic or intraabdominal infections. All isolated organisms were sensitive to imipenem with an MIC for 90% of the strains of 1 mg/l. Imipenem/cilastatin treatment resulted in rapid control of the infections in 39 of the 41 evaluable patients (95.5%). In the remaining two patients treatment had to be prematurely discontinued due to adverse effects. The causative bacterial strains were eradicated from blood in all patients who received more than one day of imipenem/cilastatin treatment but persisted sensitive to imipenem in peripheral foci in five patients (17%). Clinical and laboratory adverse reactions were noted in seven patients. In conclusion, imipenem/cilastatin was a well tolerated and effective empirical drug for treatment of septicemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Sepsis; Thienamycins

Imipenem/cilastatin is the combination of a broad spectrum beta-lactam antibiotic with dehydropeptidase I--an inhibitor of the metabolism of imipenem. Clinical trials have shown that imipenem/cilastatin given intravenously is effective in the treatment of mild, moderate or severe infections. A new milled form of imipenem has been developed for intramuscular use as a suspension with cilastatin, which provides a longer effective half-life of three to four hours with lower peak concentrations of imipenem. A multicenter clinical trial was instituted in the treatment of mild and moderate infections with 500 mg b.i.d. and 500 mg t.i.d. or 750 mg b.i.d., respectively. All 500 mg doses were suspended in saline while the 750 mg doses were in 1% lidocaine. A total of 346 (126 on 500 mg b.i.d., 70 on 500 mg t.i.d. and 128 on 750 mg b.i.d.) were entered. Another 22 patients received a combination of the two regimens. Of the total 346 patients entered, 286 were considered evaluable for efficacy. Skin and soft tissue infections were the most common followed by intra-abdominal, respiratory and urinary tract infections. Overall favorable outcomes were demonstrated in 98.7% with a range of 92 to 100%. All patients were included in the safety analysis. Clinical adverse experiences (AEs) were reported in 3.2% of patients with two AEs considered drug related. Both were pain at the injection site with 500 mg doses. No injection site pain was reported as AEs with the 750 mg doses. Laboratory AEs were reported in 17% and considered drug related in 7% (primarily liver enzymes changes).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Administration Schedule; Drug Combinations; Humans; Imipenem; Injections, Intramuscular; Thienamycins

Sixty-one hospitalized infants aged one day to six months were enrolled in an open, multicenter noncomparative clinical study of the efficacy and safety of imipenem/cilastatin. Patients weighing less than 1500 g (four males/ten females, Group 1) and those greater than or equal to 1500 g (31 males/16 females, Group 2) were analyzed separately. Total daily dose (divided into b.i.d. (27) or t.i.d. (34) regimens) ranged from 50 to 101.4 mg/kg given for 10.8 days (means, range 2 to 35 days) for Group 1 and 39.7 to 103 mg/kg given for 11.2 days (means, range 1 to 41 days) for Group 2. The investigators graded the intensity of signs and symptoms of infections as moderate or severe in 86 and 91% of patients in groups 1 and 2, respectively, and bacterial pathogens were isolated pretreatment in 43 and 32% of patients. Eighty-eight percent of all bacterial pathogens were susceptible to imipenem in vitro. The most commonly isolated pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. Patients who had confirmed bacterial infections and who did not receive concomitant antibiotics were considered evaluable for efficacy, including 6 (43%) in Group 1 and 15 (32%) in Group 2. Infection sites were (Group 1) respiratory (100%), and (Group 2) skin and skin structures (33%), urinary (11%), gastrointestinal (11%), septicemia alone (11%) and meningitis or respiratory (28% and 6% with sepsis, respectively). Safety analysis included all patients. Imipenem/cilastatin was well tolerated in 93% of Group 1 and 85% of Group 2 patients. Three patients' treatments were discontinued due to rash, oliguria or poor local tolerability. Three patients in Group 1 and four in Group 2 died; deaths were considered unrelated to imipenem/cilastatin. Results are as follows: (table; see text) In summary, 81% (17 of 21) of evaluable patients were clinically cured or improved, among whom 3 of 21 patients (14%) had serious clinical or laboratory adverse experiences which were considered possibly related to imipenem/cilastatin. These results are comparable to results reported with other single or multiple antibiotic regimens.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Infant; Infant, Low Birth Weight; Infant, Newborn; Male; Thienamycins

One hundred and four children who were hospitalized for documented or suspected non-CNS bacterial infections (56 males/48 females, 22 days to 15 years old) were treated with intravenous imipenem/cilastatin for 9.4 days (range 3 to 28 days). Children up to three years of age received 100 mg/kg/day and older children 60 mg/kg/day, administered in four divided doses. Bacterial pathogens were isolated before therapy in 85%. Diagnoses in the 74 evaluable patients included bronchopneumonia with or without empyema (20%), peritonitis complicating appendicitis (16%), skin/soft tissue abscesses (14%), septicemia (11%) and miscellaneous other infections (39%). Among evaluable patients, 95% were clinically cured or improved. One patients, a marasmic child with pneumonitis due to pseudomonas, died during therapy. One evaluable patient each with shigellosis, Klebsiella pneumoniae empyema and streptococcal pneumonia had bacteriologic eradication or suppression but, due partly to noninfectious complications, had no overall clinical improvement. Most bacterial isolates (101/108) were eradicated, including many gram-negative and gram-positive aerobes and anaerobes; three pathogens persisted (one Proteus mirabilis and one Salmonella typhi, one Staphylococcus aureus); and one Escherichia coli pyelonephritis recurred after therapy ended too early. Imipenem/cilastatin was well tolerated by 91% of children. Clinical adverse experiences (AEs), none serious except for the one death, occurred in 19%; 12% were judged possibly related to imipenem/cilastatin, but none probably or definitely related. No serious laboratory AEs occurred; the most common AEs were eosinophilia (11%), urine discoloration, and infusion site pain. Imipenem/cilastatin is well tolerated and has excellent clinical efficacy in a wide variety of pediatric infections.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Administration Schedule; Drug Combinations; Female; Humans; Imipenem; Infant; Infant, Newborn; Infusions, Intravenous; Male; Thienamycins

Imipenem/cilastatin at a dose of 0.5 g six hourly was compared to conventional combination therapy with ampicillin 0.5 g six hourly, metronidazole 0.5 g eight hourly and gentamicin 80 mg eight hourly (with dose adjustment by trough and peak serum levels) in the treatment of severe intra-abdominal infections. All antibiotics were given intravenously. Forty-five patients entered the trial. Of the 19 evaluable patients in the imipenem/cilastatin group, 16 were clinically cured with five microbiological successes and two failures. Of 24 evaluable patients in the combination group, 22 were clinically cured with one microbiological success and one failure. One patient in each group suffered an adverse effect. Patients in the I/C group tended to be older with more women and more severe infections. The origin of peritonitis was similar. I/C did not differ from combination therapy in efficacy or safety and was comparable in cost. However, I/C was easier to administer than combination therapy and there was no need for serum concentration monitoring.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Female; Gentamicins; Humans; Imipenem; Male; Metronidazole; Middle Aged; Peritonitis; Random Allocation; Thienamycins

In this open, controlled, randomized multi-clinic trial, monotherapy with imipenem/cilastatin was compared to amikacin plus piperacillin as empiric antibacterial therapy in 210 neutropenic cancer patients. Of patients randomized, 53 (25%) had bacteriologically documented infections and of those 30 had septicemia. A further 80 patients (38%) were evaluable for clinical efficacy but did not have documented infections. Seventy-seven patients (37%) were non-evaluable due to effective antibiotic treatment before the trial, early institution of other antibiotics during the trial, verified non-bacterial infections, no neutropenia or other reasons. There were no significant differences in terms of efficacy between imipenem/cilastatin and amikacin plus piperacillin but a consistent trend towards higher rates of clinical cure or improvement and of elimination of causative pathogens was noted in the imipenem/cilastatin group. In patients who were severely neutropenic (less than 0.1 x 10(9) granulocytes/l), similar cure rates were obtained in the two treatment groups--again with a tendency towards better results in the imipenem/cilastatin group. Among evaluable patients with septicemia, one patient in the imipenem/cilastatin group had persistent Staphylococcus aureus bacteremia during treatment. Five patients in the amikacin plus piperacillin group had persistent bacteremia during treatment; all but one (a Pseudomonas aeruginosa) caused by strains resistant to amikacin or piperacillin. Clinical and laboratory adverse effects were mild in the imipenem/cilastatin group although nausea was significantly more common than in the amikacin plus piperacillin group. Among patients on amikacin plus piperacillin, one died in renal failure, possibly related to treatment. Drug-related serious adverse events were reported in two additional amikacin plus piperacillin patients; one with drug fever and one with hearing loss. Microbiological adverse effects occurred in similar frequencies in the two groups. It is concluded that imipenem/cilastatin is a promising candidate for monotherapy of bacterial infections in neutropenic cancer patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Drug Resistance, Microbial; Female; Humans; Imipenem; Male; Middle Aged; Neutropenia; Penicillin Resistance; Piperacillin; Prospective Studies; Random Allocation; Thienamycins

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Drug Combinations; Female; Gentamicins; Humans; Imipenem; Male; Metronidazole; Peritonitis

Twenty-five infants and children with acute osteomyelitis (n = 7), suppurative arthritis (n = 11), or both (n = 7) were treated with imipenem and cilastatin sodium. Patients ranged in age from 5 months to 11.3 years. Needle aspiration of infected sites was performed in all patients, and 11 (44%) required further surgical drainage. Imipenem and cilastatin sodium in a dosage of 100 mg/kg/d was used for children 3 years of age or younger, while older ones received 60 mg/kg/d intravenously, divided in four equal doses. Bacterial pathogens were identified in 15 patients (60%): Staphylococcus aureus in five, Haemophilus influenzae b in four, Pseudomonas aeruginosa in two, Streptococcus pneumoniae in one, group A Streptococcus in one, Kingella kingae in one, and Citrobacter amalonaticus in one. All isolates were susceptible to imipenem in vitro. Imipenem and cilastatin therapy was continued for a median of six days followed by treatment with appropriate orally administered antibiotics. Median peak serum bactericidal titers after imipenem and cilastatin infusions were 1:512 for S aureus, 1:32 for H influenzae b, 1:512 for streptococci, and 1:16 for gram-negative rods. All but one patient with P aeruginosa osteomyelitis responded favorably to imipenem and cilastatin. The median duration until resolution of symptoms was six days. Imipenem and cilastatin infusions were well tolerated, and side effects included maculopapular rash in one patient, watery diarrhea in one, and mild transient elevation of alanine aminotransferase levels in three. Because of imipenem and cilastatin's unusually broad spectrum of activity and its relative safety, this drug combination can be used for the initial, empiric therapy of acute bone and joint infections in pediatric patients.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Arthritis, Infectious; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drainage; Drug Combinations; Female; Follow-Up Studies; Humans; Imipenem; Infant; Infusions, Intravenous; Male; Osteomyelitis; Random Allocation; Suppuration; Thienamycins

In a prospective study 43 patients (19 men, 24 women) suffering from severe bacterial infections such as peritonitis (n = 16), soft tissue infection (n = 12), pneumonia (n = 7), septicemia (n = 6), catheter sepsis (n = 2), cholangitis (n = 4), osteomyelitis (n = 3), complicated urinary tract infection (n = 2) or endocarditis (n = 1) were treated t. i. d. with short-time i. v. infusions of 0.5 g imipenem/cilastatin for five to 37 days (means = 9). All the patients were cured or significantly improved following therapy with imipenem/cilastatin alone or in combination with surgical intervention. The most frequent isolates were Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus faecalis. 58 (83%) of the 70 pathogens isolated initially were eliminated. The 12 microorganisms (gram-negative aerobic bacteria) which persisted were non-contributory to the course of the infection and had MICs between 0.32 and 4 mg/l. The MICs for 60 isolates were less than or equal to 1 mg/l; the MICs for nine isolates were in the range of 2 to 8 mg/l. One S. epidermidis isolate presented primary resistance to imipenem (MIC 16 mg/l). The tolerability was good. Phlebitis was observed in one case only. Based on our experience we conclude that monotherapy with imipenem/cilastatin at a dosage of 0.5 g t. i. d. is appropriate for the treatment of severe bacterial infections.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Postoperative Complications; Prospective Studies; Thienamycins

Topics: Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Drug Resistance, Microbial; Humans; Imipenem; Kinetics; Microbial Sensitivity Tests; Thienamycins

The clinical efficacy, tolerability and safety of imipenem/cilastatin were studied in a open, prospective trial with 63 general surgical patients suffering from bacterial infections. According to study criteria, 48 of the patients were evaluable. Clinical cure was achieved in 47 of these 48 patients (97.9%). The causative organisms were eliminated in 39 of the 47 patients cured. Clinical side-reactions were observed in 4.2% of the 63 patients treated. In 8.3% of these laboratory parameters were changed. 77 of the 78 microorganisms isolated before therapy were sensitive to imipenem (MICs 0.02-2.0 mg/l). In one patient a coagulase-negative staphylococcus with an MIC of 16 mg/l was isolated after five days of therapy.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Postoperative Complications; Prospective Studies; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Humans; Microspheres; Retrospective Studies; Shoulder Pain

To evaluate the effectiveness and safety of intra-arterial imipenem/cilastatin sodium (IPM/CS) infusion for painful interphalangeal joint osteoarthritis (OA).. Fifty-eight patients with interphalangeal joint OA who underwent intra-arterial IPM/CS infusion were retrospectively evaluated. Intra-arterial infusions were performed via percutaneous wrist arterial access. The Numerical Rating Scale (NRS), Functional Index for Hand Osteoarthritis (FIHOA), and Patient Global Impression of Change (PGIC) scale scores were assessed at intervals of 1, 3, 6, 12, and 18 months. Clinical success was evaluated based on PGIC.. All patients were followed up for at least 6 months after treatment. Of them, 30 and 6 patients were followed up for 12 and 18 months, respectively. No severe or life-threatening adverse events were encountered. The mean NRS score was 6.0 ± 1.4 at baseline, which significantly decreased to 2.8 ± 1.4, 2.2 ± 1.9, and 2.4 ± 1.9 at 1, 3, and 6 months after treatment, respectively (all P < .001). The mean NRS scores were 2.8 ± 1.7 and 2.9 ± 1.9 at 12 and 18 months, respectively, in the remaining patients. The mean FIHOA score significantly decreased from 9.8 ± 5.0 at the baseline to 4.1 ± 3.5 at 3 months (P < .001). The mean FIHOA score was 4.5 ± 3.3 at 12 months in the remaining 30 patients. The clinical success rates based on PGIC at 1, 3, 6, 12, and 18 months were 62.1%, 77.6%, 70.7%, 63.4%, and 50.0%, respectively.. Intra-arterial IPM/CS infusion is a potential treatment option for interphalangeal joint OA refractory to medical management.

Topics: Arthralgia; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Humans; Imipenem; Infusions, Intra-Arterial; Osteoarthritis; Retrospective Studies

To elucidate in vitro and in vivo characteristics and embolic properties of imipenem-cilastatin (IPM-CS) compared with hydrogel microspheres.. Particle size distribution was microscopically evaluated with 3 samples of 50 mg IPM-CS suspensions in each of 6 conditions by a mixture of contrast volume: 500 or 1000 μL and vortex mixing time: 5, 10, or 30 s. Time-dependent changes up to 3 h post-mixing were also evaluated. Fifteen male Sprague-Dawley rats (460.2 ± 5.0 g) underwent unilateral renal artery embolization using IPM-CS (n = 11) or hydrogel microspheres (n = 4). Follow-up angiography 48 h after embolization and histological evaluation, including acute tubular necrosis (ATN) and inflammation, were scored using a 5-point scale (from 0 = normal to 4 = severe).. Over 91% of IPM-CS particles were <40 μm under all in vitro conditions. With the increased contrast volume, the average particle size also increased (mean ± standard deviation: 11.6 ± 13.9 vs 16.7 ± 18.2 μm for 500 and 1000 μL iodinated contrast, P < .001); however, the impact of the mixing/elapsed time were limited. At 48 h after embolization, all cases in the IPM-CS groups (11/11) showed major to complete recanalization versus no recanalization with hydrogel microspheres (0/4) (P < .001). The following are the median ATN and inflammation grades in the cortex (ventral/dorsal) and medulla (ventral/dorsal) in both groups: IPM-CS, ATN in cortex (2/4) and medulla (1/1), inflammation in cortex (0/0) and medulla (0/0); hydrogel microspheres, ATN in cortex (4/4) and medulla (3/2), inflammation in cortex (1/1) and medulla (1/1).. IPM-CS suspension generated particles that were predominantly smaller than 40 μm and with unique short-term embolic effects, leaving predominantly peripheral ischemic changes.

Topics: Animals; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Therapy, Combination; Imipenem; Joint Diseases; Male; Rats; Rats, Sprague-Dawley

Imipenem/cilastatin sodium/relebactam is a combination of imipenem/cilastatin, a U.S. Food and Drug Administration (FDA)-approved antibiotic, and β-lactamase inhibitor relebactam which has been developed for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to drug-resistant bacterial pathogens. The combination (Recarbrio) has been designated as a qualified infectious disease product (QIDP) and obtained FDA approval in 2019 for the treatment of cUTI and cIAI caused by susceptible Gram-negative microorganisms in adult patients with limited or no alternative treatment options. The product was also approved by the European Medicines Agency (EMA) in 2020 for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.

Topics: Adult; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Infections; Cilastatin, Imipenem Drug Combination; Humans; Intraabdominal Infections; Urinary Tract Infections

We demonstrated therapeutic nonequivalence of "bioequivalent" generics for meropenem, but there is no data with generics of other carbapenems.. One generic product of imipenem-cilastatin was compared with the innovator in terms of in vitro susceptibility testing, pharmaceutical equivalence, pharmacokinetic (PK) and pharmacodynamic (PD) equivalence in the neutropenic mouse thigh, lung and brain infection models. Both pharmaceutical forms were then subjected to analytical chemistry assays (LC/MS).. The generic product had 30% lower concentration of cilastatin compared with the innovator of imipenem-cilastatin. Regarding the active pharmaceutical ingredient (imipenem), we found no differences in MIC, MBC, concentration or potency or AUC, confirming equivalence in terms of in vitro activity. However, the generic failed therapeutic equivalence in all three animal models. Its Emax against S. aureus in the thigh model was consistently lower, killing from 0.1 to 7.3 million less microorganisms per gram in 24 hours than the innovator (P = 0.003). Against K. pneumoniae in the lung model, the generic exhibited a conspicuous Eagle effect fitting a Gaussian equation instead of the expected sigmoid curve of the Hill model. In the brain infection model with P. aeruginosa, the generic failed when bacterial growth was >4 log10 CFU/g in 24 hours, but not if it was less than 2.5 log10 CFU/g. These large differences in the PD profile cannot be explained by the lower concentration of cilastatin, and rather suggested a failure attributable to the imipenem constituent of the generic product. Analytical chemistry assays confirmed that, besides having 30% less cilastatin, the generic imipenem was more acidic, less stable, and exhibited four different degradation masses that were absent in the innovator.

Topics: Animals; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Stability; Drugs, Generic; Humans; Imipenem; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Staphylococcus aureus; Therapeutic Equivalency

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Cerebral Hemorrhage; Cilastatin, Imipenem Drug Combination; Female; Humans; Male; Middle Aged

Carbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains easily develop a multi-resistance action to other potent antimicrobial agents. Nonetheless, the protective delivery of current antibiotics using nano-carriers opens a tremendous approach in the antimicrobial therapy, allowing the nano-formulated antibiotics to beat these health threat pathogens. Herein, we encapsulated imipenem into biodegradable polymeric nanoparticles to destroy the imipenem-resistant bacteria and overcome the microbial adhesion and dissemination. Imipenem loaded poly Ɛ-caprolactone (PCL) and polylactide-co-glycolide (PLGA) nanocapsules were formulated using double emulsion evaporation method. The obtained nanocapsules were characterized for mean particle diameter, morphology, loading efficiency, and in vitro release. The in vitro antimicrobial and anti adhesion activities were evaluated against selected imipenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates.. The obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2-3 h compared to the imipenem loaded PLGA and free drug. Successfully, PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. Moreover, the imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively.. These promising results indicate that polymeric nanoparticles recover the efficacy of imipenem and can be considered as a new paradigm shift against multidrug-resistant isolates in treating severe bacterial infections.

Topics: Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Infections; beta-Lactam Resistance; Biofilms; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Carriers; Drug Combinations; Drug Resistance, Multiple, Bacterial; Imipenem; Klebsiella pneumoniae; Lactic Acid; Microbial Sensitivity Tests; Nanoparticles; Particle Size; Polyesters; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Pseudomonas aeruginosa

Adequate empirical antibiotic dose selection for critically ill burn patients is difficult due to extreme variability in drug pharmacokinetics. Therapeutic drug monitoring (TDM) may aid antibiotic prescription and implementation of initial empirical antimicrobial dosage recommendations. This study evaluated how gradual TDM introduction altered empirical dosages of meropenem and imipenem/cilastatin in our burn ICU.. Imipenem/cilastatin and meropenem use and daily empirical dosage at a five-bed burn ICU were analyzed retrospectively. Data for all burn admissions between 2001 and 2011 were extracted from the hospital's computerized information system. For each patient receiving a carbapenem, episodes of infection were reviewed and scored according to predefined criteria. Carbapenem trough serum levels were characterized. Prior to May 2007, TDM was available only by special request. Real-time carbapenem TDM was introduced in June 2007; it was initially available weekly and has been available 4 days a week since 2010.. Of 365 patients, 229 (63%) received antibiotics (109 received carbapenems). Of 23 TDM determinations for imipenem/cilastatin, none exceeded the predefined upper limit and 11 (47.8%) were insufficient; the number of TDM requests was correlated with daily dose (r=0.7). Similar numbers of inappropriate meropenem trough levels (30.4%) were below and above the upper limit. Real-time TDM introduction increased the empirical dose of imipenem/cilastatin, but not meropenem.. Real-time carbapenem TDM availability significantly altered the empirical daily dosage of imipenem/cilastatin at our burn ICU. Further studies are needed to evaluate the individual impact of TDM-based antibiotic adjustment on infection outcomes in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Body Surface Area; Burn Units; Burns; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Computer Systems; Critical Illness; Drug Combinations; Drug Monitoring; Female; Humans; Imipenem; Length of Stay; Male; Meropenem; Middle Aged; Retrospective Studies; Thienamycins; Young Adult

Early, empiric, broad-spectrum antibiotics followed by de-escalation to pathogen-specific therapy is the standard of care for ventilator-associated pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used until quantitative bronchoalveolar lavage results are finalized, at which time de-escalation occurs to pathogen-specific agents. With this practice, however, alterations in antimicrobial resistance remain a concern. Our hypothesis was that this strict regimen does not alter antimicrobial susceptibility of common gram-negative VAP pathogens in our SICU.. After Institutional Review Board approval, a retrospective review of SICU-specific antibiograms was performed for the sensitivities of common gram-negative VAP pathogens. Time periods were defined as early (January-June 2005) and late (July-December 2006). Chart review of empiric and de-escalation antibiotic usage was obtained. Data were collated, and statistical significance was assessed with the chi-square test using the on-line Simple Interactive Statistical Analysis tool.. Imipenem-cilastatin was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times, respectively. Collectively, the susceptibility of gram-negative organisms to I-C did not change (early 91.4%; late 97%; p = 0.33). Individually, non-significant trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa (early 85.7%; late 90.9%; p = 0.73) and Acinetobacter baumannii (early 80%; late 100%; p = 0.13). Further, both TOB (early 77.1%; late 70.0%; p = 0.49) and LEV (early 74.3%; late 70.0%; p = 0.67) were found to maintain their susceptibility profiles. The frequency of resistant gram-positive VAPs was unchanged during the study period. Our de-escalation compliance (by 96 h) was 78% for I-C, 77.2% for TOB, and 59% for LEV. When infections requiring I-C were removed from the analysis, de-escalation compliance was improved to 92%.. In our SICU, early, empiric broad-spectrum VAP therapy followed by de-escalation to pathogen-specific agents did not alter antimicrobial resistance and is a valid practice. Further, our compliance with de-escalation practices was higher than published rates.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin; Pneumonia, Ventilator-Associated; Retrospective Studies; Tobramycin

Plasma imipenem concentrations were measured in 19 critically ill children (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual variations (2 to 4x at peak and >10x at trough concentrations) resulted in unpredictable plasma levels in several children. To avoid subtherapeutic drug levels, we recommend treatment with at least 100 mg/kg of body weight/day of imipenem-cilastatin for critically ill children requiring such therapy.

Topics: Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Illness; Cross Infection; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Infant; Infant, Newborn; Infusions, Intravenous; Male

A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against Pseudomonas aeruginosa than either 500 mg of MEM q8h (3-h infusion) or 0.5 g of imipenem-cilastatin (I-C) q6h (1-h infusion). For other pathogens, 500 mg of MEM q8h was equivalent or superior to I-C.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Pseudomonas aeruginosa; Thienamycins; Time Factors

The bactericidal exposures necessary for positive clinical outcomes among skin and soft tissue infections are largely dependent on interpatient pharmacokinetic variability and pathogen drug susceptibility. By simulating the probability of achieving target bactericidal exposures, the pharmacodynamics of three beta-lactam agents were compared against a range of pathogens implicated commonly in complicated skin and soft tissue infections.. Using Monte Carlo simulation, pharmacodynamic target attainment expressed as the percentage of the time interval during which the antibiotic concentration exceeded the minimal inhibitory concentration (%T > MIC) in serum and blister fluid was calculated for 5,000 simulated patients receiving imipenem-cilastatin 0.5 g q8h, meropenem 0.5 g q8h, piperacillin-tazobactam 3.375 g q6h, and piperacillin-tazobactam 4.5 g q8h. The pharmacokinetics for each antibiotic were derived from previously published healthy volunteer studies. The MICs for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterobacter sp., Klebsiella sp., coagulase-negative staphylococci, Proteus sp., beta-hemolytic streptococci, and Serratia sp. were taken from the MYSTIC 2003 surveillance study and weighted by the prevalence of each pathogen among 1,404 isolates collected from skin and soft tissue infections during the 2000 SENTRY study. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was added into the model at increasing resistance rates.. Imipenem-cilastatin, meropenem, and piperacillin-tazobactam 3.375 g q6h achieved greater than 90% likelihood of achieving bactericidal exposure in serum and blister fluid until the prevalence of MRSA increased beyond 10%. Piperacillin-tazobactam 4.5 g q8h achieved a lower probability of achieving bactericidal exposure than the other regimens (88.7%, p < 0.001).. When the incidence of MRSA is low, imipenem-cilastatin, meropenem and piperacillin-tazobactam 3.375 g q6h would be optimal choices for the empiric treatment of complicated skin and soft tissue infections among the regimens studied. When MRSA is suspected, a drug that retains activity against this pathogen should be considered.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Population Surveillance; Prevalence; Soft Tissue Infections; Thienamycins

Topics: Bacteria; Bacterial Infections; beta-Alanine; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Thienamycins; Treatment Failure

Antibacterial activity of biapenem (BIPM) against clinical isolates of 8 species between 2000 and 2002 was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP) and ceftazidime (CAZ). The MICs of biapenem for Gram-positive bacteria were higher than those of IPM/CS and PAPM/BP, equal to those of MEPM and lower than those of CAZ. The MICs of BIPM for Gram-negative bacteria were higher than those of MEPM, equal to those of IPM/CS and PAPM/BP, and lower than those of CAZ. Antibacterial activity of BIPM against Pseudomonas aeruginosa was equal to those of IPM/CS and MEPM and superior to those of PAPM/BP and CAZ. In conclusion, BIPM showed broad antibacterial activity against both Gram-positive and Gram-negative clinical isolates. These results suggest that BIPM is useful for the treatment of various bacterial infections.

Topics: Bacteria; Bacterial Infections; beta-Alanine; Carbapenems; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Humans; Imipenem; Infant; Infant, Newborn; Infant, Premature

To compare the cost, efficacy and cost efficacy of tazobactam/piperacillin and imipenem/cilastatin in the treatment of intra-abdominal infection.. The analysis was retrospective and based on a decision tree. Effectiveness data were obtained from 19 published clinical trials. Direct costs were quantified per patient from the time the decision was made to administer the antibacterial to the end of the first course of treatment or the end of a subsequent course of treatment, if required. The primary end-point was the cost per successfully treated patient. The cost per life saved was also analysed. Various follow-up times were taken into account.. German National Health Insurance funds.. 1744 patients with intra-abdominal infection.. Tazobactam/piperacillin (total daily dosage of 13.5 g/day) and imipenem/cilastatin (total daily dosage of 1.5 to 4 g/day). The mean duration of treatment varied from 5.5 to 8.2 days for tazobactam/piperacillin and 5 to 9.4 days for imipenem/cilastatin.. Compared with imipenem/cilastatin, treatment with tazobactam/piperacillin was more effective and the overall treatment costs were lower. In the base-case analysis, the cost-efficacy ratio (cost per successfully treated patient) was 7881 German deutschmarks (DM) for tazobactam/piperacillin and DM11,390 for imipenem/cilastatin. The incremental cost-efficacy ratio (per life saved) varied between -DM72,567 and -DM350,738 for tazobactam/piperacillin. Sensitivity analyses revealed that the results were robust against various assumptions on cost parameters, clinical outcomes and length of treatment. All costs reflect 1998 values; $US1 = DM1.85.. This study suggests that compared with imipenem/cilastatin, tazobactam/piperacillin is more cost efficacious in the treatment of intra-abdominal infections and that it offers a cost advantage through fewer relapses and lower daily therapeutic costs.

Topics: Abdomen; Adult; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cost-Benefit Analysis; Decision Trees; Drug Combinations; Drug Costs; Drug Therapy, Combination; Health Care Costs; Humans; Imipenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Protease Inhibitors; Randomized Controlled Trials as Topic; Retrospective Studies; Thienamycins

The authors present the results of a clinical investigation on the therapeutic use of carbapenem, imipenem/cilastatin in 20 patients operated on account of intraabdominal inflammatory affections, hospitalized at the intensive care unit of the Surgical Clinic of the Third Medical Faculty, Charles University, Prague in 1993. Imipenem/cilastatin was administered to patients during surgery--500 mg i.v.--and subsequently after 8--hour intervals for 5-8 days. During comprehensive treatment no superinfection developed and the patients recovered.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Postoperative Complications

The clinicobacteriological efficacy and tolerance of thienam (imipenem/cylastatin) were studied in the empirical therapy of 38 patients with severe purulent inflammatory diseases of various localization i.e. pneumonia, lung abscesses, pyothorax, peritonitis, abdominal abscesses, meningitis and brain abscesses. The treatment of all the patients with the drug was started before the data on the bacteriological investigation were available. Although the infections and the general state of the patients were extremely severe, the therapy with thienam proved to be efficient in 31 out of 35 cases (88.6 per cent) subjected to the drug efficacy estimation. The bacteriological diagnoses with respect to 24 out of 38 patients (64.7 per cent) were available later: 93.6 per cent of the isolates was sensitive to imipenem. The antimicrobial activity of imipenem against 254 clinical isolates assayed by the method of serial dilutions exceeded that of the majority of the currently used antimicrobial drugs, including aminoglycosides, 3rd generation cephalosporins and ureldopenicillins. The tolerance of thienam was good. Only in 4 out of 38 patients it was necessary to use some other drugs because of the side effects. Therefore, the use of the thienam is advisable as a drug of empirical monotherapy in patients with severe infections of the respiratory organs, abdominal cavity and central nervous system.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Humans; Imipenem; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged

The antimicrobial activity of imipenem/cilastatin (IPM/CS) was determined for a broad spectrum of 7,157 organisms isolated from the Clinical Microbiology Laboratory of Chang Gung Memorial Hospital, Linkou Medical Center, between April 1 and June 30, 1988. Ninety eight point one percent of 4,389 gram negative aerobes, 95.8% of 2391 gram positive rods, and 95.9% of 507 anaerobes, were shown to be sensitive to IPM/CS. Ninety nine point two percent of 837 Pseudomonas aeruginosa isolates were sensitive to this antibiotic. This study also disclosed that this agent was much more active against Pseudomonas aeruginosa than any other tested aminoglycosides (gentamicin, amikacin, netilmicin) or third generation cephalosporins (cefotaxime, latamoxef, ceftazidime). Twelve critically ill patients with polymicrobial and mixed infection were recruited into this trial. All patients received IPM/CS 500 mg intravenously every six hours except one patient with poor renal function had 250 mg every six hours. The average duration of therapy was 12.5 days. All patients were evaluated according to the selection criteria. IPM/CS achieved favorable clinical response in 83.7 percent. The antibiotic was well tolerated. One patient discontinued treatment because of jaundice. One patient had superinfection of fungemia. The results suggested that IPM/CS is very useful in the treatment of patients with mixed infections due to gram positive, gram negative, and anaerobic bacteriae, even when empirical therapy with other antibiotics fails.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged

The clinical and bacteriological efficacy of imipenem/cilastatin (IPM/CS) was evaluated in 30 cases of serious infections associated with hematological malignancies. 1. Among 28 evaluable cases, excellent efficacy was obtained in 6 cases and good effectiveness in 10 cases, resulting in a high clinical efficacy rate (57.1%). The clinical effectiveness of IPM/CS was not dependent on neutrophil count in peripheral blood. A 53.8% efficacy rate was observed in 26 cases which had received pretreatment with other antibiotics. 2. Antibacterial activities of IPM/CS have so far been evaluated against organisms isolated in 20 of 28 cases: 2 strains of coagulase-negative Staphylococcus, 2 strains of methicillin-resistant Staphylococcus aureus, 2 strains of Enterococcus faecalis, 9 strains of Enterobacter cloacae, and 8 other strains. 3. Among 3 evaluable cases treated with IPM/CS alone, response was good in 1 case. Among 25 patients receiving IPM/CS in combination with an aminoglycoside or a penicillin, the efficacy rate was 60%. 4. Five patients had IPM/CS-related adverse events; nausea and vomiting in 2 cases, seizures in 1 case, small increases in GOT and GPT in 2 cases, and the appearance of casts in urine sediment in 1 case. These patients, however, tolerated the complete course of therapy with IPM/CS except the 2 cases with nausea and vomiting. These results indicate that chemotherapy with IPM/CS is effective for the treatment of severe infectious diseases accompanied by hematological disorders.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Hematologic Diseases; Humans; Imipenem; Immunocompromised Host; Leukocyte Count; Male; Middle Aged; Neutrophils

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Gentamicins; Hiccup; Humans; Imipenem; Infusions, Intravenous; Male; Middle Aged; Tibial Fractures; Wound Infection

The efficacy and the safety of intramuscular imipenem/cilastatin sodium (IPM/CS) were evaluated in 22 patients with obstetric and gynecologic infections. 0.5 g/0.5 g of IPM/CS was suspended in a lidocaine solution and administered in the gluteal muscle twice a day for 3-7 days. Nineteen patients with intrauterine infections were evaluable for the clinical efficacy and 22 for the safety. 1. Clinical efficacies were excellent in 6 patients, good in 11 and poor in 2, and the efficacy rate was 89.5%. Thirteen out of 14 patients who had not responded to treatments with other previously administered antibiotics showed excellent or good responses to IPM/CS. 2. Causative bacteria were eradicated in 5 patients, decreased in 2, unchanged in 3 and replaced in 3, with an eradication rate of 61.5%. 3. Among 22 patients treated with IPM/CS, an eruption and general itching were observed in 1 patient, but no abnormal laboratory test values were observed.

Topics: Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Injections, Intramuscular; Microbial Sensitivity Tests; Middle Aged; Uterine Diseases

We evaluated the clinical efficacy and safety of intramuscular (as a new route of administration) imipenem/cilastatin sodium (IPM/CS) in patients with intrauterine infections which are typical in the field of obstetrics and gynecology. The obtained results are summarized as follows. 1. Twenty-seven patients were treated with IPM/CS, 250 mg/250 mg b.i.d. (3 patients), 500 mg/500 mg b.i.d. (22) and other dosages (a change in dosing regimen, 2). The duration of treatment ranged from 3 to 11 days and the total dosage during an entire course of treatment varied from 1.5 to 9.0 g. The drug was suspended in a lidocaine solution and administered in the gluteal muscle of the patients. 2. Clinical efficacies were excellent in 7 patients (26%), good in 19 (70%) and poor in 1 (4%) and the overall efficacy rate was 96.3%. All of the 8 patients who had not previously showed improvements with treatment by other antibiotics responded well to this drug. 3. Bacteriologically, the clinical efficacy rate was 95.8% (23/24) and the eradication rate was 76.2% (16/21). 4. No adverse effects due to the drug were observed. As abnormal laboratory test results, transient elevations of GOT and GPT were noted in one patient.

Topics: Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Injections, Intramuscular; Microbial Sensitivity Tests; Middle Aged; Uterine Diseases

The authors describe their experience with imipenem-cilastatin in 36 patients in critical conditions due to multiresistant bacterial infections. The efficacy and tolerability of the antibiotic are stressed.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Care; Drug Combinations; Drug Evaluation; Humans; Imipenem; Middle Aged

This article describes an imipenem/cilastatin (I/C) target drug program. The program, developed following completion of a drug usage evaluation study, was designed to improve I/C dosing, reduce central nervous system (CNS) adverse effects, and reduce antibiotic costs. Following completion of an inservice education program for the medical and pharmacy professional staffs, ongoing monitoring of I/C usage was accomplished through the pharmacy-based drug-dosing service. Pharmacists evaluated I/C dosage based upon culture/sensitivity results and indicators of renal function. If deemed inappropriate, the pharmacist contacted the prescribing physician with a dosage recommendation. Two hundred ten courses of I/C therapy were prescribed in the nine-month period following implementation of the target drug program; 26 cases (12 percent) required dosage adjustment. The incidence of CNS adverse effects including seizures decreased from 15 to 1 percent (p = 0.0015). A $6033 drug cost avoidance also resulted from pharmacist intervention.

Topics: Adult; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Central Nervous System Diseases; Cilastatin; Cilastatin, Imipenem Drug Combination; Cost Savings; Drug Combinations; Drug Costs; Drug Monitoring; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Kidney Diseases; Pharmacy Service, Hospital

Sixty-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) and the efficacy and safety of this drug were evaluated. 1. Fifty-nine patients were evaluable for the efficacy. Clinical efficacies were excellent in 10 patients, good in 24, fair in 11 and poor in 14, and the overall efficacy rate was 57.6%. 2. The clinical efficacy rates were 62% against septicemia and suspected septicemia, 40% against pneumonia and 100% against urinary tract infection (1 case). 3. The clinical efficacy rates when these patients were grouped according to numbers of neutrophils after treatment were: less than 100/mm3; 44.4%, 101-500/mm3; 58.3% and over 501/mm3; 60.5%. The efficacy rate was particularly excellent, 60.0%, for patients with neutrophil counts were less than 100/mm3 both before and after treatment. 4. Sixty-eight patients were evaluable for the safety. Side effects were observed in 5 patients and abnormal laboratory test values were observed in 5 patients.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Imipenem; Infusions, Intravenous; Male; Middle Aged

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.

Topics: Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Female; Hematologic Diseases; Humans; Imipenem; Infant; Male; Neoplasms; Neutropenia

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Survival Analysis; Treatment Outcome; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Safety

Topics: Acute Disease; Adult; Aged; Bacterial Infections; Chronic Disease; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Pulmonary Disease, Chronic Obstructive; Safety

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Leukocyte Count; Puerperal Disorders

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Neutropenia; Treatment Outcome

The authors report one year of clinical experience with imipenem-cilastatin, first antibiotic of thienamycin class, in the therapy and prophylaxis of postoperative infectious diseases. One hundred thirty four patients were treated with antibiotic therapy and 10 days after in 98.5% of cases a clinical remission of the disease was obtained; only in 2 patients the effect wasn't evaluable because they died for not drug-related causes. The prophylactic use of this antibiotic was limited to 34 patients with high risk of infectious diseases; only 3 cases (8.8%) showed bacterial contamination and one of them had clinical signs of disease which indicated the absolute need for antibiotic therapy. The Authors also emphasize the excellent results, the tolerability of the drug and the absence of side-effects.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Humans; Imipenem; Male; Middle Aged; Premedication

The authors describe an open study in 22 patients with febrile conditions of unknown origin who were treated with imipenem-cilastatin while waiting for routine laboratory and culture tests. These were done immediately at the patients' entry into hospital, after which imipenem-cilastatin treatment was started immediately, and was subsequently confirmed by the isolates and culture tests. The drug was found to be active and to eradicate the responsible organism in all cases. In addition, it was found to be easy to handle and not to give rise to side-effects or changes in laboratory tests.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Fever of Unknown Origin; Humans; Imipenem; Male; Middle Aged

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem

Imipenem/cilastatin sodium (IMP/CS) was administered to patients with severe infections complicated by hematological disorders and solid tumors to assess its efficacy and safety. Primary diseases in this series of 76 cases included 37 cases of hematological disorders (acute leukemia in 25 cases, malignant lymphoma in 7 cases, aplastic anemia in 3 cases and 2 other diseases) and 38 cases of solid tumors (lung cancer in 7 cases, gastric cancer in 11 cases, esophageal cancer in 6 cases, pancreatic cancer in 3 cases, bile duct cancer in 4 cases, hepatocellular cancer in 3 cases, and 4 other diseases). Following results were obtained. 1. Types of infection in hematological diseases were sepsis in 5 cases, suspected sepsis in 24 cases, pneumonia in 5 cases and 3 others. The efficacy rates were 100% in sepsis, 62.5% in suspected sepsis, 80% in pneumonia and 73% in all cases. 2. Types of infection in solid tumors were sepsis in 2 cases, suspected sepsis in 13 cases, pneumonia in 10 cases, cholecystitis in 2 cases, cholangitis in 5 cases, liver abscess in 2 cases, and 4 others. The efficacy rates were 50% in sepsis, 69.2% in suspected sepsis, 80% in pneumonia, and 71.1% in all cases. 3. IPM/CS was administered in single use in 66 cases and in combination with other antibiotics in 9 cases. The efficacy rate in the single use was 72.7% and that in the combination use was 66.7%. 4. The efficacy rate in 35 cases of first use was 71.4% and that in 40 cases of second use was 72.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Hematologic Diseases; Humans; Imipenem; Male; Middle Aged; Neoplasms; Neutrophils

Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium (IPM/CS) were performed in neonates. The results were as follow: 1. A total of 27 patients consisting of 17 mature and 10 immature infants were treated with IPM/CS. Each dose was 20 mg/20 mg/kg, and it was administered 2 approximately 3 times daily, in a 1-hour intravenous drip infusion for 3 approximately 12 days. The clinical efficacy of IPM/CS in 10 patients with bacterial infections (2 with sepsis, 3 with suspected sepsis, 2 with pneumonia, 2 with urinary tract infection and 1 with acute omphalitis) was evaluated as excellent in all patients, with an efficacy rate of 100%. All 5 causative organisms found in 5 patients (Staphylococcus aureus in 1, Staphylococcus epidermidis in 1, Escherichia coli in 2 and Flavobacterium meningosepticum in 1) were eradicated. Among 27 patients administered IPM/CS, adverse reactions were observed in 2 patients. These were rash and diarrhea. As for abnormal laboratory test values, elevations of GOT and GPT were observed. 2. MICs of IPM against 14 clinical isolates (S. epidermidis 1, S. aureus 6, Streptococcus agalactiae 4, E. coli 1, Enterobacter cloacae 1 and F. meningosepticum 1) from neonatal patients with bacterial infections were examined. IPM showed good antibacterial activity comparable to that of cefotaxime against S. agalactiae; however, the activity against methicillin-resistant S. aureus was poor. 3. Serum levels of IPM and CS were investigated in a total of 22 patients consisting of 15 mature and 7 immature infants after 20 mg/20 mg/kg of IPM/CS was administered. IPM and CS produced peak serum levels at the end of the drip infusion. In mature infants, peak serum levels of IPM and CS were 31.8 micrograms/ml (17.1 approximately 59.0 micrograms/ml) and 59.9 micrograms/ml (35.6 approximately 99.0 micrograms/ml), respectively. In low birth weight infants, these were 25.0 micrograms/ml (16.8 approximately 41.8 micrograms/ml) and 55.2 micrograms/ml (33.8 approximately 82.4 micrograms/ml), respectively. Half-lives of IPM and CS were 1.0 approximately 2.7 hrs. and 0.9 approximately 7.4 hrs. in mature infants, and 1.6 approximately 3.0 hrs. and 1.3 approximately 9.7 hrs. in immature infants, respectively. Generally the longer half-lives were observed in the younger neonates. Serum levels of CS remained higher and half-lives of CS were longer than those of IPM. The pharmacokinetics in neonates were different from those in adults or childr

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Microbial; Female; Humans; Imipenem; Infant, Newborn; Male

Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium (IPM/CS) were performed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of IPM and CS sodium were determined in 7 neonates with ages between 7 and 26 days (gestation periods were 37 to 41 weeks and birth weights were 2,410 to 3,890 g) upon 1 hour drip intravenous infusion of IPM/CS at 10 mg/10 mg/kg, or 20 mg/20 mg/kg. Mean plasma concentrations of IPM reached their peaks at the end of infusion with levels of 12.7 +/- 3.0 micrograms/ml for the group given 10 mg/10 mg/kg, and 19.1 +/- 4.1 micrograms/ml for 20 mg/20 mg/kg. The concentration of IPM in plasma showed a dose-response to the 10 mg/10 mg/kg and 20 mg/20 mg/kg dosages. Concentrations decreased with half-lives of 1.87 +/- 0.71 hours and 1.97 +/- 0.21 hours for the low and the high dosages, and plasma levels at 8 hours after administration were 0.3 +/- 0.1 microgram/ml and 0.8 +/- 0.3 microgram/ml, respectively. Mean urinary recovery rates in 8 hours after administration were 37.6 +/- 11.8% and 26.8 +/- 17.2% for the low and the high dosages. While, mean plasma concentrations and mean urinary recovery rates of CS were higher than those of IPM, mean plasma half-lives of CS were similar to IPM. 2. IPM/CS was administered to 11 neonatal patients (with ages between 1 and 26 days) of various bacterial infections, and clinical effectiveness, bacteriological efficacy and adverse reactions were evaluated. Clinical efficacies in cases including 7 with acute pneumonia and 1 each with suspected septicemia, intrauterine infection, acute urinary tract infection and periproctal abscess were judged excellent in 10 and good in 1 case, and the efficacy rate was 100%. Causative organisms isolated from these patients included 3 strains of Escherichia coli and 1 strain each of Streptococcus pyogenes, Streptococcus agalactiae Enterococcus faecalis and Haemophilus influenzae. All the organisms were eradicated by IPM/CS, thus the bacteriological eradication rate was 100%. No adverse reactions were observed, but decreased platelet in 1 patient and increased GOT in 2 patients were found as abnormal laboratory test values. These changes, however were transient, and returned to normal after discontinuation of IPM/CS. It was concluded that the clinical results of IPM/CS are indicative of excellent efficacy, safety and usefulness of the drug in the treatment of infections in neonates.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Microbial; Female; Humans; Imipenem; Infant, Newborn; Infusions, Intravenous; Male

We treated 20 febrile episodes in 14 patients with granulocytopenia under 1.0 x 10(9)/L. 6 episodes were pretreated, in 14 Imipenem/Cilastatin was the initial therapy. The age was between 36 and 78 years, mean 57 years. Predominant underlying disease was acute leukemia. 8 out of 20 episodes became afebrile. Counting only proven bacterial infections the response rate was 6 out of 12. There was a statistical difference between not pretreated and pretreated patients. The treatment had no success in the latter. There was also a significant difference between febrile episodes of patients with granulocytes increasing under treatment to those remaining unchanged. 5 of 6 of the first group but none of the 9 episodes of the second group resolved. 7 patients died while on treatment between the 9th and 32nd day after therapy had started. There was no connection between the Imipenem treatment and the deaths. Tolerance of therapy was good. The most common side effect was nausea, which was reversible with reduction of the infusion rate. Most important advantage of imipenem is the easy handling and the low inconvenience to the patient. We had only moderate efficacy in our series.

Topics: Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever of Unknown Origin; Humans; Imipenem; Male; Middle Aged; Neutropenia; Prospective Studies

Eighty-seven episodes of infection occurring in 83 patients were treated with imipenem as the sole antibiotic (1.5-4 g daily). All patients were aged 65 years or over, many with other non-infective diseases. A favourable clinical outcome (infection cured or improved) was obtained in 88% of cases. Of the 37 patients who were microbiologically evaluable, a favourable clinical outcome occurred in 92% and a favourable bacteriological outcome (pathogen eradicated or suppressed) occurred in 86% of cases. There were 13 deaths amongst the study group, which might be expected in an ill elderly population. None of the deaths was thought attributable to imipenem. Minor clinical side effects occurred in 10.6%, and one patient sustained a cerebral ischaemic episode and fits, possibly related to imipenem. No serious changes were detected in laboratory parameters.

Topics: Aged; Aged, 80 and over; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Drug Resistance, Microbial; Female; Humans; Imipenem; Male; Thienamycins

The efficacy and safety profile of imipenem/cilastatin was investigated in 94 patients with diabetes mellitus with infections of the lower extremity. Ninety-eight percent of the pathogens were susceptible to imipenem; this was higher than to other antibiotics tested. Ninety-two percent of the patients were cured (47%) or improved (45%). Bacterial eradication was achieved for 79% of the pathogens. Adverse experiences were similar to those reported previously. Imipenem-cilastatin proved to be a very effective antibiotic with a good safety profile for use in diabetic patients with lower extremity infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Diabetes Complications; Drug Combinations; Drug Evaluation; Female; Foot Diseases; Humans; Imipenem; Leg; Male; Middle Aged; Skin Diseases, Infectious; Thienamycins

Imipenem, a new carbapenem (thienamycin) beta-lactam antibiotic which is clinically used in a 1:1 combination with cilastatin, an inhibitor of renal metabolism of imipenem, was evaluated in 25 patients; 11 children and 14 neonates. A mean daily dose of 60 mg/kg was given to children and the dose in neonates was 50 mg/kg. Clinically, 21 patients were cured, two failed to respond to treatment and two were not evaluable. Pharmacokinetic studies were performed in the 11 children and in 10 of the neonates. The mean elimination half-life of imipenem was 0.87 h in children and 2.1 h in neonates. The mean cilastatin elimination half-life was 0.73 h in children and 5.1 h in neonates. This difference in half-life between children and neonates is similar to the one noted between healthy adults and adults with renal insufficiency. No accumulation of imipenem was seen in neonates studied on the first and fifth days of treatment.

Topics: Adolescent; Age Factors; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Dose-Response Relationship, Drug; Drug Combinations; Drug Evaluation; Female; Half-Life; Humans; Imipenem; Infant, Newborn; Male; Thienamycins

The efficacy and safety of intramuscularly administered imipenem/cilastatin was studied in 70 patients with mild or moderately severe bacterial infections (skin and soft tissue infections, respiratory tract infections, urinary tract infections and pelvic infections). Doses of imipenem/cilastatin ranged from 0.5 to 0.75 g twice daily. Fifty-five patients were evaluable for bacteriological efficacy; in the remaining 15 patients no pathogens were isolated or susceptibility data were lacking. MIC50 and MIC90 of imipenem were 0.12 mg/l and 0.5 mg/l, respectively, for Gram-negative pathogens isolated and 0.25 mg/l and 0.5 mg/l, respectively, for Gram-positive pathogens. Only one strain (a Flavobacterium odoratum) was resistant to imipenem. Clinical cure and bacteriological elimination was achieved in 94% of evaluable patients while 3% showed marked clinical improvement. Two patients were considered therapeutic failures. No clinical adverse effects were noted. Abnormal liver transaminases were recorded in 23% of the patients and 11% developed eosinophilia. In no patient was imipenem/cilastatin discontinued due to adverse effects. It is concluded that intramuscular imipenem/cilastatin in these patients was well tolerated and efficacious.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Middle Aged; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Humans; Imipenem; Thienamycins

Minimal inhibitory concentrations (MICs) of imipenem, ceftazidime, piperacillin, tobramycin, azthreonam and carumonam were assessed for 400 urinary isolates from hospitalized patients with complicated and/or nosocomial urinary tract infections yielding greater than or equal to 10(5) colony forming units (cfu). More than 90% of the gram-negative pathogens were sensitive to all the antibiotics tested. However, only imipenem and piperacillin exhibited MIC90 values in the therapeutic range for gram-positive pathogens (approximately half of which were staphylococci and enterococci). Perioperative prophylaxis with 0.5 g imipenem/cilastatin administered at different time intervals before the operation (up to six hours) was performed in patients undergoing resection (n = 31), respectively enucleation (n = 1) of a prostatic adenoma or lithotriptic treatment (n = 4). Imipenem yielded peak plasma concentrations of 12.2 to 134.8 mg/l (mean 49.4 mg/l). The estimated half life time in these patients was approximately three hours. Considerable intra as well as interindividual variations were found for imipenem concentrations in prostatic adenoma. However, they were sufficiently high to reach sensitive pathogens (MICs up to 1 mg/l) for up to two-and-a-half hours. Up to six hours after dosing the concentrations in prostatic secretions ranged between 1 and 2 mg/l. A total of 20 urological patients suffering from complicated urinary tract infections (15 men, five women) received a short-term i.v. infusion of 0.5 mg imipenem/cilastatin t.i.d. for seven to 16 days (median seven days). In all these patients urines were sterile during therapy as well as one to two days after therapy. Follow-up examinations performed seven to ten days after the end of treatment in 19 of these patients showed ten patients to be free of infection (55%); these patients were classified as success. Seven patients (37%) presented a relapse (same pathogen) and two patients (10%) a re-infection (different pathogen). Imipenem/cilastatin was well tolerated locally and systemically.

Topics: Adult; Aged; Aged, 80 and over; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Humans; Imipenem; Male; Middle Aged; Premedication; Prostatic Hyperplasia; Thienamycins; Tissue Distribution; Urinary Tract Infections

Seven patients were treated for bacterial infections with imipenem/cilastatin. Imipenem is a new broad-spectrum beta-lactam antibiotic with antimicrobial activity against gram-positive and gram-negative bacilli. Before and during treatment parameters of blood coagulation and platelet function were studied. Blood coagulation was not influenced by the antibiotic. But there was a temporary inhibition of collagen-induced platelet aggregation during the first days of treatment. No clinical signs of enhanced spontaneous bleeding tendency were observed.

Topics: Adult; Bacterial Infections; Blood Coagulation; Blood Platelets; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Platelet Aggregation; Thienamycins

Imipenem/cilastatin was used for the treatment of 594 bacterial infections in 545 patients at a dosage of 1.5 g/day (n = 283), 2.0 g/day (n = 129), 3.0 g/day (n = 102), or 4 g/day (n = 11). The most common indications for therapy were nosocomial pneumonias followed by intraabdominal postoperative infections, and skin and soft tissue infections. Out of 1171 bacterial strains isolated from 932 patients, seven showed primary resistance to imipenem. The causative agent was eliminated in 87% of the patients. Treatment failed in 24 of the 594 patients. In 35 patients therapy was stopped because of side effects. The most frequent side effect was local irritation at the site of intravenous application.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Retrospective Studies; Thienamycins

Imipenem/cilastatin in a doses of 1.5/day was used to treat 31 moderate to severe infections, predominantly soft tissue infections with bone involvement, in 30 surgical patients. A clinical success was achieved in 93% of the patients. In one patient with diabetic gangrene of the foot, imipenem/cilastatin treatment performed as a last resort was not able to prevent amputation. One patient died from his underlying disease while on therapy. All isolates except one Pseudomonas diminuta strain regarded as contaminant were initially sensitive to imipenem. Two Pseudomonas aeruginosa strains developed resistance by the end of therapy. Staphylococcus aureus and coagulase-negative staphylococci were the most common aetiologic agents. Only few clinical and biochemical side-effects were observed: in two cases an allergic rash appeared following several days' treatment. Four patients developed thrombocytopenia, which, however, was completely reversible after the end of therapy.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bone Diseases; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Postoperative Complications; Prospective Studies; Thienamycins

Calculated chemotherapy is based on the knowledge of the typical bacterial agents of a particular infection. From January 1983 to August 1985 bacteriological findings from surgical patients with peritonitis, septicemia or pneumonia treated in an intensive care unit were analysed. The study concentrated on those findings only which differed from previous bacteriological investigations. During the first three days 53 patients on assisted ventilation suffering from peritonitis exhibited mainly enterobacteria in their peritoneal secretions. At day 10 or later we also found bacteria from the pseudomonas group. At that time the bacterial spectrum of bronchial secretions was comparable to that of the peritoneal secretions of the same patient. After day 10, the bacterial spectrum was similar in 36 ventilated patients without peritonitis, in 56 patients suffering from post-operative pneumonia and in peritonitis patients. According to our findings, calculated chemotherapy may be based on the fact that patients with peritonitis who cannot be cured within a few days have a bacterial flora comparable to that of patients with septicemia or pneumonia. Patients with severe infections following surgery, such as potentially fatal pneumonia, generalised peritonitis or septicemia were treated with imipenem/cilastatin, according to the above definitions of calculated chemotherapy. 37 of 46 patients treated between May and December 1985, were clinically cured. Microorganisms persisted in five clinically cured patients. Development of resistance to imipenem was observed in one case. In one case treatment had to be stopped because of an allergic skin reaction. Monotherapy of peritonitis by imipenem/cilastatin appeared more satisfactory than treatment with combinations of other antibiotics.

Topics: Adult; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Peritonitis; Pneumonia; Postoperative Complications; Respiration, Artificial; Retrospective Studies; Sepsis; Thienamycins

26 patients from the surgical intensive care unit, University Hospital Lübeck, received imipenem/cilastatin for severe abdominal, respiratory or urogenital infections. 500 mg imipenem/cilastatin were infused i.v. over 30 min q. i. d. The treatment was successful in 84,6% of the patients suffering from severe infections. Two cases were considered to be failures. 36 of the 43 isolated pathogens (83.7%) were eliminated. Transitory elevations of liver enzymes were the most frequent side-reactions observed; an increase in serum creatinine, diarrhoea or fungal colonization were less common.

Topics: Abdomen; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Intensive Care Units; Male; Middle Aged; Postoperative Complications; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

In an open prospective study the efficacy and tolerance of imipenem/cilastatin was investigated in 24 critically ill patients on mechanical ventilation with nosocomial respiratory tract infection. Nine patients had previously received antibiotic therapy, eight of them with various other beta-lactam antibiotics which had failed. Imipenem was given in a dose of 1-3 g/24 h over 5-37 (mean 11) days. Seven patients were additionally treated with aminoglycosides, one patient with erythromycin. Pseudomonas aeruginosa (n = 14), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 4) and Escherichia coli (n = 3) were the potential pathogens most frequently isolated from tracheo-bronchial secretions. All of the isolates were susceptible to imipenem. 91% of the infections without and 77% with involvement of P. aeruginosa were successfully treated. Two patients who had not responded to previous treatment succumbed to the consequences of progressive respiratory distress syndrome. All of the gram-positive and 85% of the gram-negative pathogens (Pseudomonas not included) were eliminated in the course of therapy. By contrast, 64% of the isolates of P. aeruginosa persisted; half of these became imipenem-resistant. Nine patients showed adverse reactions including one case of pseudomembranous colitis or laboratory abnormalities which were all reversible. Imipenem/cilastatin proved highly effective and was relatively well tolerated; it is suitable as a single agent for the initial treatment of nosocomial respiratory tract infections in ventilated patients, although only with limitations in cases of infection due to P. aeruginosa.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Prospective Studies; Respiration, Artificial; Respiratory Insufficiency; Respiratory Tract Infections; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Humans; Imipenem; Microbial Sensitivity Tests; Thienamycins