meropenem and Soft-Tissue-Infections

In a multicenter, international, double-blind, randomized clinical trial involving hospitalized patients with complicated skin and skin-structure infections (cSSSIs), meropenem and imipenem/cilastatin (both administered 500 mg intravenously every 8 hours) were not significantly different in their efficacy and safety profiles.. The objective of the post hoc subgroup analysis discussed in the current article was to report the efficacy and tolerability of meropenem and imipenem/cilastatin for the treatment of cSSSIs in patients with or without underlying diabetes mellitus (DM).. Hospitalized patients aged > or =13 years with evidence of cSSSIs were eligible for inclusion. Patients were randomized to receive meropenem or imipenem/cilastatin, each 500 mg intravenously every 8 hours, for at least 3 days and up to a maximum of 14 days. Patients were analyzed according to the presence or absence of DM and by the pathogen(s) isolated from wound cultures at baseline, end of N treatment, and test-of-cure visits. The primary efficacy end point was clinical outcome at the posttreatment follow-up (test-of-cure) visit in the clinically evaluable and modified intent-to-treat (intent-to-treat [ITT] subjects who met all eligibility criteria) populations; this was defined as 7 to 14 days after final administration of antibiotics. The secondary efficacy end points included clinical response at the test-of-cure visit in the ITT population (ie, those who received >1 dose of study drug) and at the end of N treatment visit in the clinically evaluable and fully evaluable populations. At baseline, the end of N treatment, and the test-of-cure visits, specimens were obtained from the most extensive site of skin and skin-structure infection and were cultured for bacteria. Adverse events were monitored daily during treatment and for 30 days after the completion of all antibiotic treatment.. Of the 1076 patients enrolled in the original study, 398 had DM. The mean ages of patients with and without DM were 55 and 45 years, respectively; 17.3% of patients with DM and 6.1% of patients without DM had impaired renal function at study entry. Complex abscess was the most common infection diagnosis in both groups (patients with DM, 30.0%; patients without DM, 48.8%). The other top infections per group (patients with and without DM, respectively) were as follows: cellulitis, 24.6% and 12.4%; and ischemic/diabetic ulcers, 20.9% and 1.9%. Gram-negative aerobic and anaerobic pathogens accounted for >40% of bacterial isolates from both groups, with polymicrobial infections reported in 44.2% of patients with DM and 34.0% of patients without DM. In the clinically evaluable population, the satisfactory clinical response rate was 85.6% for patients with DM receiving meropenem and 72.4% for those receiving imipenem/cilastatin; for patients without DM, those rates were 86.6% and 89.0%, respectively. Meropenem and imipenem/cilastatin were generally well tolerated. Reported adverse events were similar between groups.. This subgroup analysis found that 500 mg every 8 hours intravenously of meropenem or imipenem/cilastatin appeared efficacious and well tolerated for the treatment of cSSSIs among these patients with and without DM.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cilastatin; Cilastatin, Imipenem Drug Combination; Diabetes Complications; Double-Blind Method; Drug Combinations; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Skin Diseases, Bacterial; Soft Tissue Infections; Thienamycins

Meropenem, a broad-spectrum carbapenem with potent in vitro activity, is postulated to be an effective monotherapy for the treatment of complicated skin and skin structure infections (cSSSI).. This multicenter, international, double-blind, randomized, prospective study of hospitalized patients with cSSSI evaluated the efficacy, safety, and tolerability of meropenem (500 mg IV q8h) versus imipenem-cilastatin (500 mg IV q8h). The primary efficacy endpoint was clinical outcome at follow-up in the clinically evaluable (CE) and modified intent-to-treat populations (MITT; patients who met eligibility criteria and received at least one dose of study drug). The study aimed to demonstrate non-inferiority (delta of 10%, 95% confidence intervals) in clinical response in the CE population. Clinical responses for all pathogens at follow-up were assessed in the fully evaluable population (CE population with baseline pathogen and follow-up cultures).. In total, 1,076 patients were enrolled. Of these, 692 patients comprised the MITT population (334 and 358 patients randomized to meropenem and imipenem-cilastatin, respectively) and 548 the CE population (261 and 287 patients randomized to meropenem and imipenem-cilastatin, respectively). Cure rates were 86.2% (meropenem) and 82.9% (imipenemcilastatin; 95% CI, -2.8, 9.3) in the CE population and 73.1% (meropenem) and 74.9% (imipenem-cilastatin; 95% CI, -8.4, 4.7) in the MITT population. The frequencies of adverse events and drug-related adverse events were similar between treatment groups.. In one of the largest studies conducted to date of hospitalized patients with cSSSI, meropenem, 500 mg IV q8h had comparable safety and efficacy to imipenem-cilastatin, 500 mg IV q8h.

Topics: Adolescent; Adult; Aged; Bacteria, Anaerobic; Cilastatin; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Male; Meropenem; Middle Aged; Skin Diseases, Bacterial; Soft Tissue Infections; Thienamycins; Treatment Outcome

Meropenem, a new carbapenem with improved stability in the presence of human dehydropeptidase-I[1], was evaluated in three prospective, multicenter, randomized, controlled clinical trials in North America. We compared the in vitro activity of meropenem and conventional antimicrobial agents for the treatment of intraabdominal, obstetric/gynecologic, and skin or soft tissue infections as well as the responses of pathogens to all of these agents. The trials of the drug for intraabdominal infection were double blind, and those for the obstetric/gynecologic and soft tissue infections were open labeled. Overall, MICs of meropenem for pathogens were lower, and the pathogen response rates were at least comparable to those for the following comparative agents: clindamycin plus tobramycin (for intraabdominal infections); clindamycin plus gentamicin (for obstetric/gynecologic infections); and imipenem and cilastatin (for skin or soft tissue infections). Meropenem has high in vitro potency and covers a broad spectrum of anaerobic and aerobic pathogens.

Topics: Abdomen; Anti-Bacterial Agents; Bacterial Infections; Double-Blind Method; Female; Genital Diseases, Female; Humans; Meropenem; Microbial Sensitivity Tests; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Thienamycins

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

Meropenem hydrochloride (MpM)-loaded nanostructured lipid carriers were designed for the effective management of skin infection caused by Staphylococcus aureus via topical route. The solvent evaporation tactic was preferred to develop nanostructured lipid carriers (NLCs). Stearic acid was used as a solid fatty acid; oleic acid was used as liquid fatty acid and Tween 80 as a surfactant. The Staphylococcus aureus burden was analyzed by pharmacodynamic studies. The skin retention was analyzed by fluorescence microscopy. Spherical shape of NLCs was confirmed by TEM. The optimum particle size of the MpM-NLCs was ~ 126.5 ± 0.9 nm with 79.1 ± 2.3% entrapment (EE) and 0.967 mV zeta potential. The in vitro release studies revealed 81.5 ± 3.1% release of drug in 48 h, while the pure drug was almost completely released (98.4 ± 1.4%) within 24 h confirming the potential of NLCs for sustained topical drug delivery. Skin permeation study also revealed better permeation of drug from NLCs than of plain drug. The prepared MpM-NLCs when stored at 4 ± 2°C for 90 days were found to be more stable when the formulation was stored at 28 ± 2°C. The S. aureus burden was analyzed by evaluating the zone of inhibition (ZOI). The ZOI of MpM alone and MpM-NLC gel was measured and compared with that of the control group. The MpM was found significantly effective when its gel was prepared with NLCs because of its enhanced adhesion property occlusion and ability to sustain release. In overall, the study's outcomes validated the relevance of NLC's composition as a vehicle for topical MpM administration in skin diseases caused by Staphylococcus aureus.

Topics: Drug Carriers; Humans; Meropenem; Nanostructures; Oleic Acid; Particle Size; Soft Tissue Infections; Staphylococcus aureus

The limited armamentarium against multidrug-resistant Gram-negative bacilli led to the development of a new generation of β-lactam/β-lactamase inhibitor combinations (BL/BLI).. To evaluate the in vitro activity of ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from patients hospitalized with skin and soft tissue infections (SSTIs) in several countries around the world.. A total of 360 P. aeruginosa isolates were consecutively collected from 47 medical centers located in Western Europe, Eastern Europe, the Asia-Pacific region, and Latin America. Susceptibility testing was performed by broth microdilution method at a monitoring laboratory. EUCAST breakpoints were applied.. Ceftazidime/avibactam (98.3% susceptible), ceftolozane/tazobactam (98.6% susceptible), and imipenem/relebactam (98.3% susceptible) were the most active compounds after colistin (100.0% susceptible) and retained activity against isolates nonsusceptible to piperacillin/tazobactam, meropenem, imipenem, and/or ceftazidime. Meropenem-vaborbactam was active against 94.2% of isolates. Ceftazidime/avibactam was the most active BL/BLI against meropenem-nonsusceptible (92.6% susceptible) and imipenem-resistant (93.8% susceptible) isolates, whereas ceftolozane/tazobactam was the most active BL/BLI against piperacillin/tazobactam-resistant (91.1% susceptible) and ceftazidime-resistant (91.7% susceptible) isolates.. The recently approved BL/BLIs demonstrated potent activity and broad coverage against contemporary P. aeruginosa isolates from patients with SSTIs.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Boronic Acids; Ceftazidime; Cephalosporins; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Soft Tissue Infections; Tazobactam

The SEP-1 measures have tied financial reimbursement to the treatment of patients with severe sepsis and septic shock. The purpose of this study was to assess the impact of a SEP-1 initiative on the utilization of broad-spectrum combination therapy (BSCT) in the emergency department (ED).. This was an IRB-approved, retrospective evaluation of adult patients who received vancomycin plus an antipseudomonal beta-lactam for a urinary tract infection (UTI) or skin or soft tissue infection (SSTI) in the ED. The primary outcome was the proportion of patients in which use of BSCT was considered appropriate based on clinical criteria. Secondary outcomes included door to antibiotic order time, door to administration time, proportion of patients continued on BSCT upon admission, duration of BSCT, and in-hospital mortality.. A total of 400 patients were included in the analysis. Following SEP-1 implementation, appropriate use of BSCT decreased by 12%, with 54% of patients in the pre-SEP-1 group meeting clinical criteria compared to 42% in the post-SEP-1 group (p = 0.028). In the subgroup of patients with a suspected UTI the appropriate use of BSCT declined by 25% (40% vs 15%, p = 0.005). The median door to first antibiotic administration time was not significantly different between groups (63 min vs 61 min, p = 0.091).. The implementation of the SEP-1 mandated measures was associated with an increase in the unnecessary use of BSCT. Additionally, no difference was seen in time to antibiotic administration. The results of this study demonstrate the negative impact that the SEP-1 mandate may have on antimicrobial utilization within the ED.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Centers for Medicare and Medicaid Services, U.S.; Early Diagnosis; Early Medical Intervention; Emergency Service, Hospital; Female; Guideline Adherence; Hospital Mortality; Hospitalization; Humans; Male; Medical Overuse; Meropenem; Middle Aged; Patient Care Bundles; Piperacillin, Tazobactam Drug Combination; Reimbursement Mechanisms; Retrospective Studies; Sepsis; Shock, Septic; Soft Tissue Infections; Time-to-Treatment; United States; Urinary Tract Infections; Vancomycin

A 45-year-old man with dilated cardiomyopathy presented with acute leg pain and erythema suggestive of necrotising fasciitis. Initial surgical exploration revealed no necrosis and treatment for a soft tissue infection was started. Blood and tissue cultures unexpectedly grew a Gram-negative bacillus, subsequently identified by an automated broth microdilution phenotyping system as an extended-spectrum β-lactamase producing Escherichia coli. The patient was treated with a 3-week course of antibiotics (ertapenem followed by ciprofloxacin) and debridement for small areas of necrosis, followed by skin grafting. The presence of E. coli triggered investigation of both host and pathogen. The patient was found to have previously undiagnosed liver disease, a risk factor for E. coli soft tissue infection. Whole genome sequencing of isolates from all specimens confirmed they were clonal, of sequence type ST131 and associated with a likely plasmid-associated AmpC (CMY-2), several other resistance genes and a number of virulence factors.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactams; Ciprofloxacin; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Ertapenem; Escherichia coli; Escherichia coli Infections; Floxacillin; Follow-Up Studies; Genome, Bacterial; Gentamicins; Humans; Liver Diseases; Male; Meropenem; Middle Aged; Sequence Analysis, DNA; Soft Tissue Infections; Thienamycins; Treatment Outcome; Vancomycin

Bacillus cereus is an aerobic, spore-forming, gram-positive rod. It has historically been associated with "fried rice syndrome," a foodborne diarrheal and emetic illness resulting from eating fried rice dishes that have been sitting at room temperature for hours. We report the case of a 9-year-old boy who developed culture-positive B cereus fasciitis of the right lower extremity after being impaled on a tree branch. This case report further elucidates and emphasizes the importance of recognizing B cereus as a possible cause of severe soft-tissue infection. It must be included in the differential diagnosis of gas gangrene and necrotizing fasciitis.

Topics: Anti-Bacterial Agents; Bacillus cereus; Child; Clindamycin; Debridement; Fasciitis; Fasciotomy; Gram-Positive Bacterial Infections; Humans; Lower Extremity; Male; Meropenem; Reoperation; Soft Tissue Infections; Therapeutic Irrigation; Thienamycins; Vancomycin; Wounds, Penetrating

In recent years, carbapenem-resistant Acinetobacter baumannii infections have been responsible for outbreaks in medical facilities. A 35-year-old Japanese woman developed a skin and soft tissue infection due to carbapenem-resistant A. baumannii. The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23. We selected a combination therapy consisting of intravenous ampicillin-sulbactam and meropenem. No changes were observed in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, or serum creatinine during therapy, and carbapenem-resistant A. baumannii was not detected in wound exudates 3 days after therapy initiation. In our patient's case, combination therapy with ampicillin-sulbactam and meropenem was successful. Thus, combination therapy with ampicillin-sulbactam and meropenem is effective against skin and soft tissue infection due to carbapenem-resistant A. baumannii. Combination therapy with intravenous ampicillin-sulbactam and meropenem may be an option for skin and soft tissue infections due to carbapenem-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Ampicillin; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Drug Therapy, Combination; Female; Humans; Meropenem; Microbial Sensitivity Tests; Skin Diseases, Bacterial; Soft Tissue Infections; Sulbactam; Thienamycins; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Ciprofloxacin; Fractures, Open; Humans; Male; Meropenem; Mycoses; Pyrimidines; Soft Tissue Infections; Thienamycins; Triazoles; Voriconazole; Wound Infection

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