cilastatin--imipenem-drug-combination and Urinary-Tract-Infections

Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.

Topics: Anti-Bacterial Agents; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Databases, Bibliographic; Doripenem; Drug Combinations; Female; Humans; Imipenem; Levofloxacin; Male; Research Design; Treatment Outcome; Urinary Tract Infections

Of the new antimicrobials available for the treatment of urinary tract infections (UTIs), aztreonam and imipenem/cilastatin represent two structurally unique, but distinct, classes of beta-lactam antibiotics. Aztreonam has a directed spectrum of activity covering gram-negative bacilli usually associated with UTIs. In comparative clinical trials of patients with complicated UTIs, aztreonam is well-tolerated and is as effective as conventional control regimens, including aminoglycosides. On the other hand, the antimicrobial spectrum of imipenem/cilastatin includes not only gram-negative bacilli but also gram-positive cocci and anaerobes. As such, this broad-spectrum antibiotic should be reserved for the treatment of mixed infections.

Topics: Aged; Anti-Bacterial Agents; Aztreonam; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Male; Thienamycins; Urinary Tract Infections

Relebactam, a novel class A/C β-lactamase inhibitor developed as a fixed-dose combination with imipenem/cilastatin, restores imipenem activity against imipenem-nonsusceptible gram-negative pathogens.. This phase 3, multicenter, open-label, noncomparative study (NCT03293485) evaluated relebactam/imipenem/cilastatin (250 mg/500 mg/500 mg) dosed every 6 h for 5-14 days in Japanese patients with complicated intra-abdominal infections (cIAIs) or complicated urinary tract infections (cUTIs), including those with secondary sepsis. Sepsis was defined as an infection-induced systemic inflammatory response syndrome, with a documented positive blood culture; patients meeting these protocol-defined criteria were evaluated for efficacy against sepsis.. Of 83 patients enrolled, 81 patients (cIAI, n = 37; cUTI, n = 44) received ≥1 dose of study treatment. Escherichia coli was the most common baseline pathogen isolated in both patients with cIAI and cUTI. Adverse events (AEs) were reported in 74.1% (n = 60/81) of patients, and drug-related AEs occurred in 18.5% (n = 15/81). The most common AEs were diarrhea and nausea (8.6%). Serious AEs occurred in nine patients, including one death, but none were considered treatment related. The primary efficacy endpoint for patients with cIAI was clinical response at end of treatment (EOT) in the microbiologically evaluable (ME) population, and for patients with cUTI was microbiological response at EOT in the ME population. The proportion of cIAI and cUTI patients achieving favorable responses were 85.7% (n = 24/28) and 100.0% (n = 39/39), respectively. All patients with sepsis (cIAI, n = 1; cUTI, n = 5) achieved a favorable composite clinical and microbiological response at EOT.. A favorable safety and efficacy profile for relebactam/imipenem/cilastatin was observed in Japanese patients with cIAI and cUTI.

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

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

Carbapenem-resistant Gram-negative bacteria represent the highest priority for addressing global antibiotic resistance. Cefiderocol (S-649266), a new siderophore cephalosporin, has broad activity against Enterobacteriaceae and non-fermenting bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, including carbapenem-resistant strains. We assessed the efficacy and safety of cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infection in patients at risk of multidrug-resistant Gram-negative infections.. Intravenous infusion of cefiderocol (2 g) three times daily was non-inferior compared with imipenem-cilastatin (1 g each) for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration. Clinical trials of hospital-acquired pneumonia and carbapenem-resistant infections are ongoing.. Shionogi & Co Ltd, Shionogi Inc.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefiderocol; Cephalosporins; Cilastatin, Imipenem Drug Combination; Colony Count, Microbial; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Protease Inhibitors; Treatment Outcome; Urinary Tract Infections; Urine; Young Adult

The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem non-susceptible pathogens.. To explore relebactam's safety, tolerability and efficacy, we conducted a randomized (1:1:1), controlled, Phase 2 trial comparing imipenem/cilastatin+relebactam 250 mg, imipenem/cilastatin+relebactam 125 mg and imipenem/cilastatin alone in adults with complicated urinary tract infections (cUTI) or acute pyelonephritis, regardless of baseline pathogen susceptibility. Treatment was administered intravenously every 6 h for 4-14 days, with optional step-down to oral ciprofloxacin. The primary endpoint was favourable microbiological response rate (pathogen eradication) at discontinuation of intravenous therapy (DCIV) in the microbiologically evaluable (ME) population. Non-inferiority of imipenem/cilastatin+relebactam over imipenem/cilastatin alone was defined as lower bounds of the 95% CI for treatment differences being above -15%.. At DCIV, 71 patients in the imipenem/cilastatin + 250 mg relebactam, 79 in the imipenem/cilastatin + 125 mg relebactam and 80 in the imipenem/cilastatin-only group were ME; 51.7% had cUTI and 48.3% acute pyelonephritis. Microbiological response rates were 95.5%, 98.6% and 98.7%, respectively, confirming non-inferiority of both imipenem/cilastatin + relebactam doses to imipenem/cilastatin alone. Clinical response rates were 97.1%, 98.7% and 98.8%, respectively. All 23 ME patients with imipenem non-susceptible pathogens had favourable DCIV microbiological responses (100% in each group). Among all 298 patients treated, 28.3%, 29.3% and 30.0% of patients, respectively, had treatment-emergent adverse events. The most common treatment-related adverse events across groups (1.0%-4.0%) were diarrhoea, nausea and headache.. Imipenem/cilastatin + relebactam (250 or 125 mg) was as effective as imipenem/cilastatin alone for treatment of cUTI. Both relebactam-containing regimens were well tolerated. (NCT01505634).

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Cilastatin; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Middle Aged; Prospective Studies; Pyelonephritis; Urinary Tract Infections; Young Adult

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

Therapeutic efficacy of the combined regimen, imipenem/cilastatin (IPM/CS) plus vancomycin (VCM), was examined in a total of 13 patients infected with MRSA (10 patients with pneumonia, 2 with sepsis and 1 with urinary tract infection). Based on the results of determination of FIC indices, in vitro combined effects were synergistic in 4 strains and additive in 3 strains. There was, however, no apparent correlation between the in vitro combined effect in terms of FIC index and clinical outcome. No side effects or abnormal laboratory findings were observed. The average daily doses of IPM/CS and VCM were 1.2 g and 1.25 g and the average administration periods were 17.5 and 14.9 days, respectively. The present results suggested that simultaneous use of IPM/CS and VCM at the standard doses could yield an enhancement of both bacteriological and clinical efficacies in treatment of the patients with MRSA infection.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Methicillin Resistance; Middle Aged; Pneumonia, Staphylococcal; Staphylococcal Infections; Urinary Tract Infections; Vancomycin

An intramuscular preparation of imipenem/cilastatin (IPM/CS, 500 mg/500 mg) was administered to 59 patients with complicated urinary tract infections (UTI; cystitis and pyelonephritis) to evaluate its efficacy and safety. The obtained results are summarized as follows: In patients with cystitis, evaluations based on daily frequencies of administration were also performed. 1) According to the treating doctors, the drug showed an overall efficacy rate of 80% (45/56 patients). The efficacy rate was 89% in patients with cystitis treated by a u.i.d. regimen. Among patients treated by a b.i.d. regimen, the efficacy rate was 67% for cystitis cases and 84% for pyelonephritis cases. 2) When clinical efficacy was assessed according to the criteria for UTI drug efficacy evaluation, the drug was 'markedly effective' in 14 patients, 'effective' in 23, and ineffective in 11 patients, for an efficacy rate of 77% (37/48 patients). 3) The microbiological eradication rate was 88% (59/67 strains). The rate was 95% (20/21 strains) for Gram-positive bacteria and 85% (39/46 strains) for Gram-negative bacteria. The efficacy for Enterobacter faecalis and Pseudomonas aeruginosa was 100% and 73%, respectively. 4) As side effects, pain at the injection site was reported by one patient and abnormal laboratory test values were observed in 2 patients. All of these reactions were mild and resolved shortly after the completion of treatment. Based on these findings, it is concluded that this intramuscular preparation of IPM/CS is effective for treating complicated urinary tract infections.

Topics: Adolescent; Aged; Aged, 80 and over; Bacteria; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Imipenem; Injections, Intramuscular; Male; Middle Aged; Urinary Tract Infections

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

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

Endocarditis due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a rare but challenging condition. Its treatment relies on carbapenems alone or in combination, and no alternative has been described to date. The cephamycin cefoxitin has been used for treatment of mild ESBL-producing Enterobacteriaceae infections.. We report two patients with nosocomial endocarditis due to ESBL-producing Escherichia coli and Klebsiella pneumoniae who underwent clinical failure or adverse event, respectively, during treatment with imipenem-cilastatin. The first patient was subsequently treated with cefoxitin combined with ciprofloxacin with a favorable outcome. In the second patient, the endocarditis relapsed following a 6-week treatment with cefoxitin and fosfomycin. In time-kill assays, the cefoxitin/ciprofloxacin and cefoxitin/fosfomycin combinations showed synergistic effect.. These cases illustrate that cefoxitin is an interesting alternative to carbapenems, even in severe infections such as endocarditis. Pharmacokinetic optimization and combination with another synergistic antibiotic should be considered whenever possible.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefoxitin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Endocarditis; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

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

Topics: Cefiderocol; Cephalosporins; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Humans; Urinary Tract Infections

Topics: Cefiderocol; Cephalosporins; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Humans; Urinary Tract Infections

Topics: Cefiderocol; Cephalosporins; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Humans; Urinary Tract Infections

Topics: Cefiderocol; Cephalosporins; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Humans; Urinary Tract Infections

Elderly patients, in particular, have been reported to develop psychiatric side effects from antibiotics. Clarithromycin, quinolones, sulfamethoxazole-trimethoprim, isoniazid, penicillin, and cephalosporins have been reported to cause psychosis. This case report bridges a void in the medical literature with regards to the psychiatric adverse effects of imipenem-cilastatin.. A 64-year-old Hispanic man in septic shock due to urinary tract infection was initiated on imipenem-cilastatin and mechanically ventilated, following admission to hospital. His mentation was normal for 72 hours after extubation and discontinuation of sedatives and opioids, following which he was noted to be in acute psychosis. Our patient's imipenem-cilastatin dose had been increased 24 hours prior to his violent visual and auditory hallucinations because his renal function had improved. The physical examination and laboratory tests did not reveal evidence of a new central nervous infection or endocrinopathy. His mentation improved after his antibiotic was switched to ceftriaxone, based on culture and sensitivity testing. Similar psychiatric symptoms developed 2 months later when he was treated with imipenem for a recurrent urinary tract infection. His symptoms again resolved with modification of his antibiotic regimen.. Endocrine dysfunctions (thyroid, adrenal, and pituitary disorders) and toxic ingestions are medical disorders known to cause brief psychotic episodes. Fluoroquinolones, penicillins, and trimethoprim-sulfamethoxazole are common antibiotics associated with this rare adverse effect. Several pharmacokinetic hypotheses have been proposed for this adverse effect: (1) N-methyl-D-aspartate receptor hypofunctioning, (2) sequential blockade of folic acid production, (3) inhibition of prostaglandin E2 and proinflammatory cytokine production, (4) increased central dopamine turnover, and (5) accumulation of toxic levels of the drug. Pre-existing psychopathology, relevant comorbidities, slow acetylation status, and increased permeability of the blood-brain barrier have been suggested to make patients more prone to developing psychosis. According to the literature, this psychiatric manifestation resolves within 2 weeks of discontinuing the offending agent. There appears to be underreporting of the psychiatric manifestations of imipenem-cilastatin, contrary to post-marketing surveillance data. It is imperative that physicians recognize these psychiatric side effects of antibiotics, because they are a fundamental treatment option.

Topics: Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Male; Middle Aged; Psychoses, Substance-Induced; Shock, Septic; Urinary Tract Infections

Klebsiella pneumoniae New Delhi metallo-beta-lactamase-1 (NDM-1) strains have recently become a new threat in kidney transplant recipients due to the strains' resistance to almost all antibiotics, including carbapenems.. We present a case series of 3 patients with urinary tract infections (UTIs) caused by multiresistant K pneumoniae NDM-1 strains who were treated with the same protocol. Genotyping sequencing with pulsed-field gel electrophoresis was performed in all cases.. All patients were male and had undergone kidney transplantation 4, 7, and 8 months, respectively, before the admission. Combined antibiotic therapy consisting of imipenem/cilastatin in maximal doses, gentamicin and/or colistin for 21 to 27 days, followed by oral fosfomycin, was used in all cases. There were no further UTI episodes in 2 patients at the 12-month visit. Three months after initial treatment, the third patient presented with leukocyturia with no clinical symptoms and a urine culture positive for K pneumonia NDM-1 strain. Interestingly, the strain was susceptible to trimethoprim/sulfamethoxazole despite resistance in previous urine culture samples. The patient was successfully treated with trimethoprim/sulfamethoxazole 2 × 960 mg/d for 3 weeks followed by 480 mg/d and 3 doses of fosfomycin. Genotyping sequencing revealed identical DNA restriction fragments in bacterial strains from 2 patients. In the third case, although a difference in 2 restriction fragments was observed, the strain was considered related to the others.. In cases of UTI caused by K pneumoniae NDM-1 strains, prolong combined treatment followed by oral fosfomycin prophylaxis can be successful. Strain genotyping should be performed to optimize further treatment protocols in such cases.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Drug Combinations; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; Fosfomycin; Genotype; Gentamicins; Humans; Imipenem; Kidney Transplantation; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

A 47-year-old woman was hospitalized because of urinary-tract infection. She was treated with antibiotics for 6 days. However, severe watery diarrhea and pyrexia developed 6 days after stopping administration of antibiotics. Stool, throat and blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA) and negative for Clostridium difficile DI toxin. In spite of administration of VCM, she died of septic shock. At autopsy, macroscopic observation revealed a pseudomembrane in the ileum. MRSA enterocolitis can occur in patients with antibiotic-related diarrhea, and physicians should be aware of its rapid clinical course and possible lethal outcome.

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Enterocolitis, Pseudomembranous; Female; Humans; Imipenem; Methicillin Resistance; Middle Aged; Staphylococcal Infections; Staphylococcus aureus; Urinary Tract Infections

Clinical efficacy of sodium imipenem/cilastatin was studied on 45 patients with complicated urinary tract infections, on whom prior antimicrobial agents were ineffective. A 0.5g dose of IPM/CS was administered by drop infusion twice a day for 5 days. The clinical efficacy was evaluated according to the criteria of the Japanese UTI committee. Of a total of 65 strains, 29 strains of gram positive bacteria and 36 strains of gram negative bacteria, were detected as causative microbials. Bacteriologically, 23 strains of gram positive bacteria (79%) and 34 strains of gram negative bacteria (94%) were eradicated following the treatment. S. aureus, E. faecalis and Flavobacterium sp. were less sensitive to IPM/CS. Overall clinical effectiveness rate of IPM/CS in the present study was 87%. Adverse drug side effects were observed in six patients, namely they were eruption, headache and slight elevation of serum transaminase. These findings suggest that IPM/CS is an effective agent for the treatment of complicated UTI even when the prior medicine was ineffective.

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

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: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Enzyme Inhibitors; Female; Humans; Imipenem; Inpatients; Male; Middle Aged; Safety; Urinary Tract Infections; Urologic Diseases

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

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