cilastatin--imipenem-drug-combination and Abscess

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

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

We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen.

Topics: Abscess; Adult; Aged; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Clindamycin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Peritonitis; Prospective Studies; Severity of Illness Index; Tobramycin

Mycobacterium abscessus subsp. massiliense (MMA) comprises a group of non-tuberculous, rapidly growing mycobacteria. Although MMA can cause pulmonary diseases, surgical site infections, and disseminated diseases, aortic endograft infection has not been reported. Here, we describe the first case of aortic endograft infection caused by MMA.. Two months after stent-graft insertion for an abdominal aortic aneurysm, an 85-year-old man was admitted with fever and abdominal pain and was diagnosed with aortic endograft infection. Despite 14 days of meropenem and vancomycin intravenous administration, periaortic fluid pooling increased as compared to that before antibiotic administration. The abscess was drained, and fluorescent acid-fast staining of the abscess fluid revealed bacilli. We conducted genetic tests on the genes hsp65, rpoB, and sodA, performed Whole Genome Sequencing (WGS), and identified the organism as MMA. Intravenous imipenem-cilastatin (IPM/CS), amikacin (AMK), and oral clarithromycin (CAM) were administered. After 2 months, oral CAM and sitafloxacin were administered because the abscess had decreased in size. However, after 6 weeks, the abscess increased in size again. Antimicrobial susceptibility testing of the drainage fluid from the abscess resulted in the isolation of an MMA strain that had acquired resistance to CAM. Intravenous IPM/CS, AMK, and oral linezolid were added to the treatment regimen along with oral CAM and STFX. However, he was not fully cured and died 6 months later. Neither the full-length erythromycin ribosome methyltransferase (erm)(41) gene nor the rrl or rpIV gene mutations were found by Sanger sequencing in the pre- and post-treatment strains. Whole-genome sequence analysis of the post-treatment strain revealed mutations in genes with no previous reports of association with macrolide resistance.. Aortic endograft infection caused by MMA strain is extremely rare; nonetheless, MMA should be suspected as the causative microorganism when broad-spectrum antimicrobials are ineffective.

Topics: Abscess; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Cilastatin, Imipenem Drug Combination; Clarithromycin; Drug Resistance, Bacterial; Humans; Macrolides; Male; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Stents

Infection with methicillin-resistant Staphylococcus aureus (MRSA) has become a worldwide problem and is no longer acquired only in a hospital setting. Community-associated MRSA is an emerging pathogen of increasing interest to both obstetricians and neonatologists, reported in all three trimesters of pregnancy and postpartum, and in neonatal intensive care units, leading to severe outcomes, including neonatal death. This case report describes a serious and potentially life-threatening infection (including wound abscess, septicemia, septic thrombophlebitis, and septic pulmonary emboli) that developed in an otherwise healthy postpartum woman who had screened positive for MRSA in nares, vagina, and rectum at the time of her prior admission in labor as part of a research study. We conclude that asymptomatic nasal, vaginal, and rectal colonization with MRSA occurs in pregnancy and may be a risk factor for serious systemic infection after delivery.

Topics: Abscess; Anti-Bacterial Agents; Anticoagulants; Carrier State; Cesarean Section; Cilastatin; Cilastatin, Imipenem Drug Combination; Drainage; Drug Combinations; Female; Heparin; Humans; Imipenem; Methicillin-Resistant Staphylococcus aureus; Pregnancy; Puerperal Infection; Pulmonary Embolism; Radiography; Sepsis; Staphylococcal Infections; Surgical Wound Infection; Thrombophlebitis; Vancomycin; Young Adult

We present a case of sepsis caused by isolated sphenoiditis.. The case being described concerns 61-year-old woman treated at the Department of Occupational Diseases of Wroclaw Medical University due to body temperature maintaining for 2 months at above 38 degrees C, leucocytosis reaching 14-16 thousand and weight loss of about 4 kg. Detailed diagnostics did not confirm the preliminary diagnosis of system or neoplastic disease. Bacteriological blood examination revealed the presence of staphylococcus aureus susceptible to Vancomycin and Tienam. The attempt of pharmacological treatment did not produced the expected effect. NMR examination of the facial skeleton proved partial shadowing of the Sphenoidal sinus. The patient was admitted for surgical treatment. After the sphenoidal sinus was cut open, mucopurulent contents was found inside. During microbiological examination, staphylococcus aureus with identical susceptibility was cultured from the mucopurulent contents. After 3-week guided antibiotic therapy, permanent temperature regression and permanent improvement of the patient's condition were achieved.. Surgical treatment combined with intensive antibiotic therapy caused the complete regression of symptoms.. Isolated sphenoiditis occurs rarely but it still is a serious diagnostic and therapeutic problem. Diagnosis delay and disease progress may lead to life-threatening complications.

Topics: Abscess; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Middle Aged; Radiography; Sepsis; Sphenoid Sinus; Sphenoid Sinusitis; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

A deep-seated Pseudomonas aeruginosa mouse kidney abscess model was used to compare the therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, with that of clinically relevant standard drugs. Following 50 mg/kg oral doses, twice daily for five consecutive days, clinafloxacin produced a 4 log decrease in mean bacterial count, the greatest decrease of all drugs tested. The same dosage regimen resulted in complete bacterial eradication in 88% of the kidneys. No other compound produced total bacterial clearance in 50% of the kidneys at the highest dose tested.

Topics: Abscess; Animals; Anti-Infective Agents; Area Under Curve; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Fluoroquinolones; Half-Life; Imipenem; Kidney; Kidney Diseases; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Quinolones; Treatment Outcome

Topics: Abscess; Cilastatin; Cilastatin, Imipenem Drug Combination; Diabetes Complications; Diabetic Foot; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Microsurgery; Vasodilator Agents

Cefamandole, cefoxitin, cefotetan, ceftizoxime, imipenem plus cilastatin, and ampicillin plus sulbactam were compared in the eradication of subcutaneous abscess in mice caused by Bacteroides fragilis group organisms and Escherichia coli alone or in combination. The abscesses were examined 5 d after inoculation. B. fragilis group reached log10.1-11.0 organisms per abscess and E. coli log11.6-12.5. Imipenem plus cilastatin significantly reduced (in 6.9-10.6 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Ampicillin plus sulbactam reduced the numbers of all B. fragilis group (in 4.2-7.2 logs) but was less effective against E. coli (reduction of 1.8-4.2 logs). Cefoxitin was effective in significantly reducing (in 4.9-6.2 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Cefotetan was effective against B. fragilis (reduction of 5.1-6.6 logs) and E. coli alone or in combination but did not reduce the number of Bacteroides thetaiotaomicron, Bacteroides vulgatus, and Bacteroides ovatus. Ceftizoxime was effective against only B. ovatus (reduction of 3.7-5.8) and E. coli (reduction of 6.0-8.1 logs); it did not reduce the number of other organisms. Cefamandole was effective against only E. coli and was not effective against any member of the B. fragilis group. These in vivo data confirm the in vitro activity of these antimicrobials.

Topics: Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cefotetan; Cefoxitin; Ceftizoxime; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Imipenem; Male; Mice; Skin Diseases; Sulbactam