meropenem and Abdominal-Abscess

Meropenem is a carbapenem antibiotic approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and pediatric bacterial meningitis (in patients >or=3 months of age). In clinical trials, it also has shown efficacy as initial empirical therapy for the treatment of nosocomial pneumonia. Unlike other beta-lactam antibiotics, including third-generation cephalosporins, carbapenems have shown activity against extended-spectrum beta-lactamase-producing and AmpC chromosomal beta-lactamase-producing bacteria. Compared with imipenem, meropenem is more active against gram-negative pathogens and somewhat less active against gram-positive pathogens, and it does not require coadministration of a renal dehydropeptidase inhibitor. In most comparative trials, clinical and bacteriological response rates with imipenem and meropenem were similar. Compared with clindamycin/tobramycin, meropenem is associated with a reduced length of hospital stay and a shorter duration of therapy among patients with complicated intra-abdominal infections. Meropenem is well tolerated by children and adults and has an acceptable safety profile. Alternative meropenem dosing strategies for the optimization of outcomes are under investigation.

Topics: Abdominal Abscess; Bacteria; Bacterial Infections; Cross Infection; Humans; Infant; Meningitis, Bacterial; Meropenem; Pneumonia; Skin Diseases, Bacterial; Thienamycins

Complicated intra-abdominal infections (cIAIs) require surgical intervention and empiric antibacterial therapy. Doripenem, a broad-spectrum carbapenem, provides coverage of key gram-negative and -positive aerobes and anaerobes encountered in cIAI.. This study was designed to compare the efficacy and safety profile of doripenem and meropenem in hospitalized adult patients with cIAI.. In this prospective, multicenter, doubleblind, noninferiority study, hospitalized adults with cIAI were randomly assigned to receive doripenem 500 mg IV q8h or meropenem 1 g IV q8h. After a minimum of 9 doses and adequate clinical improvement (relative to before the start of IV study drug, decreased body temperature and white blood cell count, improved or absent signs and symptoms of cIAI, and return of normal bowel function), patients could be switched to oral amoxicillin/clavulanate. Antibacterial therapy (IV plus subsequent oral) was given for a total of 5 to 14 days. The coprimary efficacy end points were the clinical cure rate (complete resolution or significant improvement of signs or symptoms of the index infection) in patients microbiologically evaluable (>or=1 baseline pathogen isolated from an intra-abdominal culture that was susceptible to both IV study drug therapies) at the test-of-cure (TOC) visit (21-60 days after the completion of study drug therapy) and the clinical cure rate in the microbiological modified intent-to-treat (mMITT) population (a bacterial pathogen identified at baseline, regardless of its susceptibility to the study drug). Noninferiority was concluded if the lower limit of the 2-sided 95% CI for the difference (doripenem minus meropenem) in the proportion of patients classified as clinical cures was >or=-15%.. A total of 476 patients were enrolled. The microbiologically evaluable population (319 patients) was 62.7% male and 67.7% white, with a mean age and weight of 46.7 years and 77.2 kg, respectively. In this population, doripenem and meropenem were associated with clinical cure rates at the TOC visit of 85.9% and 85.3%, respectively. The corresponding treatment difference was 0.6% (95% CI, -7.7% to 9.0%); this difference was not statistically significant. Similarly, in the mMITT population (385 patients), the clinical cure rates were 77.9% and 78.9%, respectively, and the corresponding 1.0% treatment difference was not statistically significant (95% CI, -9.7% to 7.7%). Clinical cure rates were not significantly different between the 2 treatment arms in key subgroups (eg, age, sex, race, baseline Acute Physiology and Chronic Health Evaluation II score, primary infection site). Microbiological eradication rates for common pathogens isolated at study entry were not significantly different between the 2 treatment groups. Doripenem was well tolerated in the population studied. In the intent-to-treat population (471 patients), 83.0% and 78.0% of patients experienced >or=1 adverse event (AE) and 13.2% and 14.0% experienced >or=1 serious AE in the doripenem and meropenem treatment arms, respectively. In the doripenem and meropenem treatment arms, AEs resulted in study drug discontinuation in 5.1% and 2.1% of patients and death in 2.1% and 3.0% of patients, respectively.. The present study found that doripenem (500 mg q8h) was effective in the treatment of cIAI, was therapeutically noninferior to meropenem (1 g q8h), with a safety profile not significantly different from that of meropenem in this selected population of patients with cIAI.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Double-Blind Method; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Thienamycins

The objectives of this study were to develop a meropenem population pharmacokinetic model using patient data and use it to explore alternative dosage regimens that could optimize the currently used dosing regimen to achieve higher likelihood of pharmacodynamic exposure against pathogenic bacteria. We gathered concentration data from 79 patients (ages 18-93 years) who received meropenem 0.5, 1, or 2 g over 0.5- or 3-hour infusion every 8 hours. Meropenem population pharmacokinetic analysis was performed using the NONMEM program. A 2-compartment model fit the data best. Creatinine clearance, age, and body weight were the most significant covariates to affect meropenem pharmacokinetics. Monte Carlo simulation was applied to mimic the concentration-time profiles while 1 g meropenem was administrated via infusion over 0.5, 1, 2, and 3 hours. The 3-hour prolonged infusion improved the likelihood of obtaining both bacteriostatic and bactericidal exposures most notably at the current susceptibility breakpoints.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Community-Acquired Infections; Creatinine; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Models, Biological; Monte Carlo Method; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Thienamycins; Time Factors

The empiric antibiotic treatment of intraabdominal infections is in constant evolution. Monotherapy appears to be a desirable goal because of the simplicity of its administration, lack of toxic effects and wide spectrum.. A multicentre, prospective, randomized, open study was carried out to compare two antibiotic regimens in the treatment of intraabdominal infections in patients undergoing surgery. Ninety-eight consecutive patients were randomly allocated into two groups. One group (GM, n = 51) received meropenem (1 g/8 h) and the other (GCM, n = 47) a combination of cefotaxime (2 g/8 h) plus metronidazol (0.5 g/8 h). Clinical and bacteriological responses were assessed at the end of treatment and at 2-4 weeks.. The severity of patients as assessed by the APACHE II score was similar in both groups (GM: 7.2 and GCM: 8.1). Three patients in each group could not be evaluated due to premature interruption of treatment or deviation from the protocol. The mean duration of treatment was 7.4 days in GM and 7.9 days in GCM. A satisfactory clinical response was obtained in 95% of patients in both groups. 31 patients (61%) in GM and 26 patients (55%) in GCM were bacteriologically evaluable. Bacteriological erradication was achieved in 94% of patients in GM and in 92% of patients in GCM.. Meropenem is a good alternative for single antibiotic therapy in intraabdominal infections of moderate severity.

Topics: Abdomen; Abdominal Abscess; Adult; Aged; Bacterial Infections; Cefotaxime; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Metronidazole; Middle Aged; Peritonitis; Prospective Studies; Thienamycins

In a randomized, double-blind clinical trial conducted at 13 medical centers, meropenem (1,000 mg given iv every 8 hours) was compared with the combination of clindamycin (900 mg every 8 hours) plus tobramycin (5 mg/[kg.d] in three divided doses) given iv for the treatment of intra-abdominal infections that required surgery and parenteral antibiotic therapy. At the end of treatment, efficacy data on patients who met study inclusion criteria (intent-to-treat) were available for 132 of 215 patients in the meropenem group and 134 of 212 patients in the clindamycin/tobramycin group; 120 (91%) of 132 intent-to-treat patients in the meropenem group were cured, 115 (86%) of 134 intent-to-treat patients in the clindamycin/tobramycin group were cured (P value, not significant). Of the patients treated with meropenem and considered evaluable according to the study protocol, 89 (92%) of 97 were cured, and 81 (86%) of 94 patients treated with clindamycin/tobramycin and considered evaluable were cured. Bacteriologic response rates for all evaluable patients (n = 191) were 96% (93 of 97 patients) among those randomized to the meropenem arm and 93% (87 of 94) among those randomized to the clindamycin/tobramycin arm. Adverse events occurred with similar frequency in both treatment groups; neither seizures nor deaths related to treatment were reported for any patients in either group. The results of this trial demonstrated that meropenem, together with appropriate surgical intervention, was safe and effective in the treatment of patients who had bacterial intra-abdominal infections, most of which were secondary to complicated appendicitis.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Anti-Bacterial Agents; Appendicitis; Bacteria, Anaerobic; Clindamycin; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Gram-Negative Aerobic Bacteria; Gram-Positive Bacteria; Humans; Male; Meropenem; Middle Aged; Thienamycins; Tobramycin; Treatment Outcome

The immune responses against isolated microorganisms in patients with intraabdominal infections treated with meropenem or imipenem/cilastatin were investigated. Fifty-nine patients received meropenem 500 mg t.i.d. intravenously for 3-21 days (mean 5.4 days) and 50 patients imipenem/cilastatin 500 mg/500 mg t.i.d. intravenously for 3-17 days (mean 5.1 days). Three serum samples were taken from each patient, the first sample at admission, the second sample between three and seven days after start of antibiotic treatment, and the third sample between 14 and 28 days later. Ninety-eight per cent of the patients in the meropenem group and 95% of the patients in the imipenem/cilastatin group were cured. There was no difference in the clinical outcome between the two treatment groups. Escherichia coli, Bacteroides fragilis group, anaerobic cocci, Staphylococcus epidermidis, and Klebsiella spp. predominated among the isolated microorganisms. Thirty-nine patients in the meropenem group had significant immune responses against one or more of the isolated microorganisms while 31 patients in the imipenem/group had significant responses. E. coli and B. fragilis gave rise in antibody titres in most patients indicating that these species are the most important pathogens in intraabdominal infections.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Antibodies, Bacterial; Bacteria, Aerobic; Bacteria, Anaerobic; Carbapenems; Cilastatin; Fluorescent Antibody Technique; Humans; Imipenem; Injections, Intravenous; Meropenem; Middle Aged; Thienamycins

Data on the microbiological epidemiology of Intra-Abdominal Abscesses (IAAs) are very scarce. We aimed to study the microbiological epidemiology of these infections in order to optimize empirical antibiotic therapy.. Between January 2015 and December 2020, we retrospectively analyzed all IAAs files in our hospital. Clinical and microbiological data such as antibiotic susceptibilities were collected.. We studied 243 IAA cases. All in all, 139 (57.2%) IAAs were healthcare-associated and 201 (82.7%) were drained. The highest risk situations for IAAs were appendicitis (n = 69) and diverticulitis (n = 37). Out of the 163 microbiologically documented infections, 136 (81.9%) were polymicrobial. Enterobacterales (n = 192, 36.1%), Enterococcus sp. (n = 84, 17.6%) and anaerobes (n = 66, 16.1%) were the most frequently identified bacteria. Gram-negative bacteria were susceptible to amoxicillin-acid clavulanic, piperacillin-tazobactam, cefotaxime, meropenem in 55.2%, 84.9%, 77.6% and 99.5% of cases, respectively. Concerning Gram-positive bacteria, the susceptibility rate was 81.8% for amoxicillin-clavulanic acid, piperacillin-tazobactam and meropenem, and decreased to 63.4% for cefotaxime.. This study highlights the polymicrobial profile of IAAs and their low susceptibility to amoxicillin and clavulanic acid. The piperacillin-tazobactam association remained the most appropriate empirical antibiotic therapy.

Topics: Abdominal Abscess; Amoxicillin; Anti-Bacterial Agents; Cefotaxime; Humans; Meropenem; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Efficacies of ceftazidime-avibactam (4:1 w/w) and ceftazidime were tested against ceftazidime-susceptible (bla

Topics: Abdominal Abscess; Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Ceftazidime; Disease Models, Animal; Drug Combinations; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Rats; Thienamycins

Leishmaniasis and melioidosis are frequently reported from the North Central Province of Sri Lanka. However, only one case of co-infection of the two diseases has been reported to date over the world. This is a case report of a patient who had co-infection with cutaneous leishmaniasis and melioidosis and was successfully treated and recovered from the illness.. A 61 year old female patient with diabetes mellitus presented with fever for one month's duration and was found to have hepatosplenomegaly and an ulcer over the left arm. She had elevated inflammatory markers and blood culture grew Burkholderia pseudomallei and serum was highly positive for melioidosis antibodies. A slit skin smear of the ulcer showed Leishmania amastigotes.. Melioidosis and leishmaniasis are emerging infectious diseases in endemic countries and can be severe. The high prevalence rates in Sri Lanka should keep the treating physicians' threshold for suspicion low for these two diseases.

Topics: Abdominal Abscess; Burkholderia pseudomallei; Ceftazidime; Coinfection; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Melioidosis; Meropenem; Middle Aged; Sri Lanka; Thienamycins

Topics: Abdominal Abscess; Anti-Bacterial Agents; Cellulitis; Clindamycin; Combined Modality Therapy; Common Variable Immunodeficiency; Debridement; Drug Substitution; Female; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Infusions, Subcutaneous; Meropenem; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Necrosis; Pyoderma Gangrenosum; Reoperation; Staphylococcal Infections; Thienamycins; Vancomycin; Wound Infection

Topics: Abdominal Abscess; Anti-Bacterial Agents; Drainage; Emphysema; Escherichia coli Infections; Female; Humans; Meropenem; Middle Aged; Portal Vein; Portography; Pyelonephritis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Humans; Imipenem; Meropenem; Thienamycins

Children with a perforated or gangrenous appendix become clinically stable after medical and/or surgical therapy but often remain in the hospital solely to complete parenteral antibiotic therapy. This prospective study investigates the outcomes when children who meet specified criteria are discharged to complete parenteral antibiotic therapy at home.. Children age 1 to 17 years with appendicitis complicated by generalized peritonitis or intraabdominal abscess were eligible to participate. Subjects whose fever was decreasing, who were able to tolerate oral liquids and for whom further parenteral antibiotic therapy was deemed necessary were discharged from the hospital to receive outpatient parenteral antiinfective therapy (OPAT) with meropenem. Therapy was administered by a family member and supervised by home care nurses. Study personnel visited the home daily to collect data on adverse events, compliance and resource utilization. Pa tients served as their own controls in models of reduced hospitalization and net cost savings.. Discharged on average on the fourth postoperative day, 87 children received 4.5 +/- 2.1 days of OPAT. Six (7%) children were subsequently readmitted for complications including bowel obstruction (4 children), intraabdominal abscess (1 child) and pleural effusion (1 child). Another child developed a viral syndrome during OPAT. All other patients recovered uneventfully. Six (7%) children discontinued meropenem prematurely because of rash (4 patients) or diarrhea (2 patients). According to models in which each day of OPAT replaced a day of inpatient care, discharge to OPAT reduced hospitalization by 42 +/- 15% and saved a median of $2908 (10th to 90th percentile range, $1,077 to $4,707) per patient.. Convalescent phase OPAT is a cost-effective alternative to continued hospitalization for children with complicated appendicitis who are clinically stable yet require further parenteral antibiotic therapy.

Topics: Abdominal Abscess; Adolescent; Anti-Bacterial Agents; Appendicitis; Child; Child, Preschool; Cohort Studies; Convalescence; Home Infusion Therapy; Home Nursing; Hospital Costs; Humans; Infant; Meropenem; Models, Econometric; Patient Discharge; Peritonitis; Prospective Studies; Thienamycins