meropenem and Pneumonia

The appearance and spread of new mechanisms of bacterial resistance to antibiotics is a serious health problem. One of the most difficult resistance mechanisms to treat is the production of carbapenemases. Carbapenemase KPC is one of those mechanisms with few therapeutic options. Meropenem-vaborbactam has shown great efficacy against this type of microorganism, both from a clinical and microbiological point of view. Its good pharmacokinetics, including in the lung, and its safety profile make meropenem-vaborbactam an excellent therapeutic option. Finally, the absence of resistance genesis during treatment seems to indicate that its efficacy will be long-lasting.

Topics: Anti-Bacterial Agents; Boronic Acids; Humans; Meropenem; Pneumonia

Pneumonia is a prevalent infection of lower respiratory tract caused by infected lungs. Length of stay (LOS) in hospital is one of the simplest and most important indicators in hospital activity that is used for different purposes. The aim of this study is to explore the important factors affecting the LOS of patients with pneumonia in hospitals.. The clinical data set for the study were collected from 387 patients in a specialized hospital in Iran between 2009 and 2015. Patients discharge summary includes their demographic details, reasons for admission, prescribed medications for the patient, the result of laboratory tests, and length of treatment.. The proposed model in the study demonstrates the way various scenarios of data processing impact on the scale efficiency model, which points to the significance of the pre-processing in data mining. In this article, some methods were utilized; it is noteworthy that Bayesian boosting method led to better results in identifying the factors affecting LOS (accuracy 95.17%). In addition, it was found that 58% of patients younger than 15 years old and 74% of the elderly within the age range of 74-88 were more vulnerable to pneumonia disease. Also, it was found that the Meropenem is a relatively more effective medicine compared to other antibiotics which are used to treat pneumonia in the majority of age groups. Regardless of the impact of various laboratory findings (including CRP, ESR, WBC, NA, K), the patients LOS decreased as a result of Meropenem.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Algorithms; Anti-Bacterial Agents; Bayes Theorem; Data Mining; Databases, Factual; Decision Trees; Female; Humans; Iran; Length of Stay; Male; Meropenem; Middle Aged; Neural Networks, Computer; Patient Admission; Patient Discharge; Patient Discharge Summaries; Pneumonia; Predictive Value of Tests; Risk Factors; Thienamycins; Time Factors; Treatment Outcome; Young Adult

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

To Compare the clinical efficacy and safety of meropenem with a 3-hour extended infusion or conventional 30-minute infusion regimen in treatment of hospital acquired pneumonia (HAP) in intensive care unit (ICU) patients.. An open-label randomized controlled clinical trial was conducted. 100 HAP patients, admitted to ICU of Qilu Hospital of Shandong University, who needed meropenem therapy were enrolled from September 1st, 2012 to September 30th, 2013. The patients were randomly divided into two groups. Patients who did not conform to the study protocol were excluded. A total of 78 patients were included for the study of clinical efficacy evaluation, with 38 cases in study group, and 40 in control group. The patients in study group received intravenous 1 g of meropenem (dissolved in 40 mL saline) within 10 minutes, and followed by the remaining 750 mg by continuous intravenous infusion for 3 hours, and the treatment was repeated every 8 hours. The patients in control group received meropenem by injection of 1 g (dissolved in 40 mL saline), i.e. by intravenous infusion within 30 minutes every 8 hours. This regime was carried out for at least 7 days. Clinical efficacy, bacterial clearance rate, improvement of critical illness scoring, and safety were observed and compared after meropenem withdrawal between two groups.. Compared with control group, the clinical cure rate and 28-day survival rate in study group were significantly increased [clinical cure rate: 71.1% (27/38) vs. 42.5% (17/40), χ² = 6.461, P=0.011; survival rate: 81.6% (31/38) vs. 60.0% (24/40), χ² = 4.364, P=0.037]. The improvement of clinical pulmonary infection score (CPIS) and sequential organ failure assessment (SOFA) score in study group were more marked than those in control group (difference of CPIS score: -3.47 ± 2.48 vs. -1.50 ± 2.48, t=-3.513, P=0.001; difference of SOFA score: -2.10 ± 2.38 vs. -1.00 ± 2.21, t=-0.800, P=0.037). There were no significant differences in duration of meropenem treatment, acute physiology and chronic health evaluation II (APACHEII) score, procalcitonin (PCT), duration of mechanical ventilation, ICU stay days, secondary infection, and bacterial clearance rate between two groups. The main adverse reactions observed were transient elevation of liver enzymes and diarrhea in both groups, but no significant difference in their incidence was found between study and control groups [elevated liver enzymes: 28.9% (11/38) vs. 30.0% (12/40), χ² = 0.010, P=0.919; diarrhea: 7.9% (3/38) vs. 10.0% (4/40), χ² = 0.000, P=1.000].. Compared with conventional regime of 30-minute infusion of meropenem in the treatment of HAP in ICU patients, the clinical efficacy can be improved, the severity of the disease can be reduced, the recovery of organ failure and long-term prognosis can be improved with 3 hour extended infusion of meropenem.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Infusions, Intravenous; Intensive Care Units; Meropenem; Pneumonia; Protein Precursors; Respiration, Artificial; Thienamycins; Time Factors

An analysis of subjects with concurrent bacteraemia and either nosocomial pneumonia, complicated intra-abdominal infection or complicated urinary tract infection from six phase 3 clinical trials demonstrated similar cure rates and clearance of bacteraemia in patients treated with doripenem and comparator agents.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Female; Humans; Imipenem; Intraabdominal Infections; Male; Meropenem; Ofloxacin; Pneumonia; Thienamycins; Treatment Outcome; Urinary Tract Infections

Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but has not been tested in neonates. We compared the steady-state pharmacokinetics (PK) of meropenem given as a short (30-min) or prolonged (4-h) infusion to very-low-birth-weight (gestational age, <32 weeks; birth weight, <1,200 g) neonates to define the appropriate dosing regimen for a phase 3 efficacy study. Short (n = 9) or prolonged (n = 10) infusions of meropenem were given at a dose of 20 mg/kg every 12 h. Immediately before and 0.5, 1.5, 4, 8, and 12 h after the 4th to 7th doses of meropenem, blood samples were collected. Meropenem concentrations were measured by ultrahigh-performance liquid chromatography. PK analysis was performed with WinNonlin software, and modeling was performed with NONMEM software. A short infusion resulted in a higher mean drug concentration in serum (C(max)) than a prolonged infusion (89 versus 54 mg/liter). In all but two patients in the prolonged-infusion group, the free serum drug concentration was above the MIC (2 mg/liter) 100% of the time. Meropenem clearance (CL) was not influenced by postnatal or postmenstrual age. In population PK analysis, a one-compartment model provided the best fit and the steady-state distribution volume (V(ss)) was scaled with body weight and CL with a published renal maturation function. The covariates serum creatinine and postnatal and gestational ages did not improve the model fit. The final parameter estimates were a V(ss) of 0.301 liter/kg and a CL of 0.061 liter/h/kg. Meropenem infusions of 30 min are acceptable as they balance a reasonably high C(max) with convenience of dosing. In very-low-birth-weight neonates, no dosing adjustment is needed over the first month of life.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Creatinine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Enterocolitis, Necrotizing; Female; Gram-Negative Bacteria; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Infusions, Intravenous; Male; Meropenem; Models, Statistical; Pneumonia; Sepsis; Software; Thienamycins

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Critical Illness; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Middle Aged; Pneumonia; Sepsis; Thienamycins

To evaluate the in-vitro activity of ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-relebactam and comparator agents against contemporary Pseudomonas aeruginosa isolates from US hospitals.. In total, 3184 isolates were collected consecutively from 71 US medical centres in 2020-2021, and susceptibility tested by reference broth microdilution. Clinical Laboratory Standard Institute breakpoints were applied.. Ceftazidime-avibactam [97.0% susceptible (S)], ceftolozane-tazobactam (98.0%S), imipenem-relebactam (97.3%S) and tobramycin (96.4%S) were the most active agents against the aggregate P. aeruginosa isolate collection, and retained good activity against piperacillin-tazobactam-non-susceptible, meropenem-non-susceptible and multi-drug-resistant (MDR) isolates. All other antimicrobials tested showed limited activity against piperacillin-tazobactam-non-susceptible, meropenem-non-susceptible and MDR isolates. The most common infections were pneumonia (45.9%), skin and skin structure infections (19.0%), urinary tract infections (17.0%) and bloodstream infections (11.7%); ceftazidime-avibactam, ceftolozane-tazobactam and imipenem-relebactam showed consistent activity against isolates from these infection types. Susceptibility to piperacillin-tazobactam and meropenem was lower among isolates from pneumonia compared with other infection types.. Ceftazidime-avibactam, ceftolozane-tazobactam and imipenem-relebactam were highly active, and exhibited similar coverage against a large contemporary collection of P. aeruginosa isolates from US hospitals. Cross-resistance among the newer β-lactams/β-lactam inhibitors (BL/BLIs) varied markedly; ≥72.1% of isolates resistant to one of the three newer BL/BLIs approved for P. aeruginosa treatment remained susceptible to at least one of the other two BL/BLIs, indicating that all three should be tested in the clinical laboratory. These three BL/BLIs represent valuable therapeutic options for P. aeruginosa infection.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Ceftazidime; Cephalosporins; Drug Combinations; Hospitals; Humans; Imipenem; Lactams; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Pseudomonas aeruginosa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR P. aeruginosa pneumonia.. We ventilated 18 pigs with monolateral MDR P. aeruginosa pneumonia for up to 102 h. At 24 h after the bacterial challenge, the animals were randomized to receive 72 h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM + AMK). We dosed IV MEM at 25 mg/kg every 8 h and inhaled AMK at 400 mg every 12 h. The primary outcomes were the P. aeruginosa burden and histopathological injury in lung tissue. Secondary outcomes included the P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers.. In a swine model of monolateral MDR P. aeruginosa pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Meropenem; Microbial Sensitivity Tests; Models, Theoretical; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Swine

Topics: Anti-Bacterial Agents; Carbapenems; Cefepime; Humans; Imipenem; Klebsiella; Klebsiella pneumoniae; Ligands; Meropenem; Metal Nanoparticles; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Monobactams; Nanoparticles; Pneumonia; Porins; Spectroscopy, Fourier Transform Infrared; Zinc Oxide

It is well documented that inappropriate use of antimicrobials is the major driver of antimicrobial resistance. To combat this, antibiotic stewardship has been demonstrated to reduce antibiotic usage, decrease the prevalence of resistance, lead to significant economic gains and better patients' outcomes. In Nigeria, antimicrobial guidelines for critically ill patients in intensive care units (ICUs), with infections are scarce. We set out to develop antimicrobial guidelines for this category of patients.. A committee of 12 experts, consisting of Clinical Microbiologists, Intensivists, Infectious Disease Physicians, Surgeons, and Anesthesiologists, collaborated to develop guidelines for managing infections in critically ill patients in Nigerian ICUs. The guidelines were based on evidence from published data and local prospective antibiograms from three ICUs in Lagos, Nigeria. The committee considered the availability of appropriate antimicrobial drugs in hospital formularies. Proposed recommendations were approved by consensus agreement among committee members.. Candida albicans and Pseudomonas aeruginosa were the most common microorganisms isolated from the 3 ICUs, followed by Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. Targeted therapy is recognized as the best approach in patient management. Based on various antibiograms and publications from different hospitals across the country, amikacin is recommended as the most effective empiric antibiotic against Enterobacterales and A. baumannii, while colistin and polymixin B showed high efficacy against all bacteria. Amoxicillin-clavulanate or ceftriaxone was recommended as the first-choice drug for community-acquired (CA) CA-pneumonia while piperacillin-tazobactam + amikacin was recommended as first choice for the treatment of healthcare-associated (HA) HA-pneumonia. For ventilatorassociated pneumonia (VAP), the consensus for the drug of first choice was agreed as meropenem. Amoxycillin-clavulanate +clindamycin was the consensus choice for CAskin and soft tissue infection (SSIS) and piperacillin-tazobactam + metronidazole ±vancomycin for HA-SSIS. Ceftriaxone-tazobactam or piperacillin-tazobactam + gentamicin was consensus for CA-blood stream infections (BSI) with first choice+regimen for HA-BSI being meropenem/piperacillin-tazobactam +amikacin +fluconazole. For community-acquired urinary tract infection (UTI), first choice antibiotic was ciprofloxacin or ceftriaxone with a catheter-associated UTI (CAUTI) regimen of first choice being meropenem + fluconazole.. Data from a multicenter three ICU surveillance and antibiograms and publications from different hospitals in the country was used to produce this evidence-based Nigerian-specific antimicrobial treatment guidelines of critically ill patients in ICUs by a group of experts from different specialties in Nigeria. The implementation of this guideline will facilitate learning, continuous improvement of stewardship activities and provide a baseline for updating of guidelines to reflect evolving antibiotic needs.. Il est bien établi que l’utilisation inappropriée des antimicrobiens est le principal moteur de la résistance aux antimicrobiens. Pour lutter contre ce phénomène, il a été démontré que la bonne gestion des antibiotiques permettait de réduire l’utilisation des antibiotiques, de diminuer la prévalence de la résistance, de réaliser des gains économiques significatifs et d’améliorer les résultats pour les patients. Au Nigéria, les directives antimicrobiennes pour les patients gravement malades dans les unités de soins intensifs (USI), souffrant d’infections, sont rares. Nous avons entrepris d’élaborer des lignes directrices sur les antimicrobiens pour cette catégorie de patients.. Un comité de 12 experts, composé de microbiologistes cliniques, d’intensivistes, de médecins spécialistes des maladies infectieuses, de chirurgiens et d’anesthésistes, a collaboré à l’élaboration de lignes directrices pour la prise en charge des infections chez les patients gravement malades dans les unités de soins intensifs nigérianes. Les lignes directrices sont basées sur des données publiées et des antibiogrammes prospectifs locaux provenant de trois unités de soins intensifs de Lagos, au Nigeria. Le comité a pris en compte la disponibilité des médicaments antimicrobiens appropriés dans les formulaires des hôpitaux. Les recommandations proposées ont été approuvées par consensus entre les membres du comité.. Candida albicans et Pseudomonas aeruginosa étaient les microorganismes les plus fréquemment isolés dans les trois unités de soins intensifs, suivis par Klebsiella pneumoniae, Acinetobacter baumannii et Escherichia coli. La thérapie ciblée est reconnue comme la meilleure approche pour la prise en charge des patients. Sur la base de divers antibiogrammes et publications provenant de différents hôpitaux du pays, l'amikacine est recommandée comme l'antibiotique empirique le plus efficace contre les entérobactéries et A. baumannii, tandis que la colistine et la polymixine B se sont révélées très efficaces contre toutes les bactéries. L'amoxicilline-clavulanate ou la ceftriaxone ont été recommandées comme médicaments de premier choix pour les pneumonies communautaires, tandis que la pipéracilline-tazobactam + amikacine ont été recommandées comme médicaments de premier choix pour le traitement des pneumonies associées aux soins. Pour les pneumonies acquises sous ventilation mécanique (PAV), le consensus sur le médicament de premier choix est le méropénem. L'amoxycilline-clavulanate +clindamycine était le choix consensuel pour les infections de la peau et des tissus mous et la pipéracilline-tazobactam + métronidazole ±vancomycine pour les infections de la peau et des tissus mous. HA-SSIS. Ceftriaxone-tazobactam ou pipéracilline-tazobactam + gentamicine a fait l'objet d'un consensus pour les infections de la circulation sanguine de l'AC (BSI), le premier choix de régime pour les HA-BSI étant le méropénem/pipéracilline-tazobactam +amikacine +fluconazole. Pour les infections urinaires communautaires, l'antibiotique de premier choix était la ciprofloxacine ou la ceftriaxone, le régime de premier choix pour les infections urinaires associées à un cathéter étant le meropenem +fluconazole.. Les données issues d’une surveillance multicentrique de trois unités de soins intensifs, d’antibiogrammes et de publications de différents hôpitaux du pays ont été utilisées par un groupe d’experts de différentes spécialités nigérianes pour élaborer ces lignes directrices sur le traitement antimicrobien des patients gravement malades dans les unités de soins intensifs, fondées sur des données probantes et spécifiques au Nigeria. La mise en œuvre de ces lignes directrices facilitera l’apprentissage, l’amélioration continue des activités de gestion et fournira une base de référence pour la mise à jour des lignes directrices afin de refléter l’évolution des besoins en antibiotiques.. Antimicrobiens, Résistance aux antimicrobiens, Gestion des antibiotiques, Lignes directrices, Soins intensifs, Unité de soins intensifs, Infections associées aux soins de santé.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Clavulanic Acid; Community-Acquired Infections; Critical Illness; Cross Infection; Fluconazole; Humans; Meropenem; Microbial Sensitivity Tests; Nigeria; Piperacillin, Tazobactam Drug Combination; Pneumonia; Prospective Studies; Urinary Tract Infections

Topics: Adult; Amikacin; Anti-Bacterial Agents; Brain Abscess; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis; Meropenem; Microbial Sensitivity Tests; Pneumonia; Sulfamethoxazole

Critical illness reduces β-lactam pharmacokinetic/pharmacodynamic (PK/PD) attainment. We sought to quantify PK/PD attainment in patients with hospital-acquired pneumonia.. Meropenem plasma PK data (n = 70 patients) were modelled, PK/PD attainment rates were calculated for empirical and definitive targets, and between-patient variability was quantified [as a coefficient of variation (CV%)].. Attainment of 100% T>4×MIC was variable for both empirical (CV% = 92) and directed (CV% = 33%) treatment.. Individualization is required to achieve suggested PK/PD targets in critically ill patients.

Topics: Anti-Bacterial Agents; Critical Illness; Hospitals; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Pneumonia; Prospective Studies

The antibiotic-resistant Klebsiella pneumoniae (Kp) has become a significant crisis in treating pneumonia. Low-frequency ultrasound (LFU) is promising to overcome the obstacles. Mice were infected with bioluminescent Kp Xen39 by intratracheal injection to study the therapeutic effect of LFU in combination with antibiotics. The counts per second (CPS) were assessed with an animal biophoton imaging system. Bacterial clearance, histopathology, and the concentrations of cytokines were determined to evaluate the therapeutic effect. LC-MS/MS was used to detect the distribution of antibiotics in the lung and plasma. LFU in combination with meropenem (MEM) or amikacin (AMK) significantly improved the behavioural state of mice. The CPS of the LFU combination group were more significantly decreased compared with those of the antibiotic alone groups. The average colony-forming units of lung tissue in the LFU combination groups were also lower than those of the antibiotic groups. Although no significant changes of cytokines (IL-6 and TNF-α) in plasma and bronchoalveolar lavage fluid were observed, LFU in combination with antibiotics showed less inflammatory damage from histopathological results compared with the antibiotic-alone groups. Moreover, 10 min of LFU treatment promoted the distribution of MEM and AMK in mouse lung tissue at 60 and 30 min, respectively, after dosage. LFU could enhance the effectiveness of MEM and AMK in the treatment of Kp-induced pneumonia, which might be attributed to the fact that LFU could promote the distribution of antibiotics in lung tissue and reduce inflammatory injury.

Topics: Animals; Anti-Bacterial Agents; Chromatography, Liquid; Cytokines; Klebsiella; Klebsiella pneumoniae; Meropenem; Mice; Pneumonia; Tandem Mass Spectrometry

Meropenem-vaborbactam is approved to treat hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), in Europe. Meropenem-vaborbactam activity was evaluated against 3,193

Topics: Anti-Bacterial Agents; Boronic Acids; Enterobacteriaceae; Hospitals; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia; Whole Genome Sequencing

Topics: Anti-Bacterial Agents; Critical Illness; Cross Infection; Humans; Meropenem; Pneumonia; Thienamycins

The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) is a global health problem due to its high mortality and limited treatment options. Combination antimicrobial therapy is reported to be effective against CRE in vitro; however, its efficacy in vivo has not been thoroughly evaluated. Thus, this study assessed the efficacy of combination therapy of meropenem (MEPM) and amikacin (AMK) in a carbapenem-resistant Klebsiella pneumoniae (CR-Kp) mouse model of pneumonia.. Agar-based bacterial suspension of CR-Kp clinical isolates was inoculated into the trachea of BALB/c mice. Treatment was initiated 6 h post infection, with 100 mg/kg MEPM every 6 h, 100 mg/kg AMK every 12 h, or in combination; survival was evaluated for 7 days. The number of viable bacteria in the lungs, lung histopathology, and neutrophil counts in broncho-alveolar lavage fluid (BALF) were evaluated 42 h after infection.. This study demonstrates in vivo efficacy of MEPM and AMK combination therapy against CR-Kp pneumonia.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pneumonia

Topics: Cephalosporins; Cross Infection; Double-Blind Method; Humans; Meropenem; Pneumonia; Tazobactam

Infections caused by fusobacteria have a wide clinical spectrum, and in certain patients, they can lead to severe systemic illness. We report the case of an immunocompromised young woman who presented with severe pneumonia complicated by parapneumonic pleural effusion, despite wide-spectrum antibiotic treatment.

Topics: Adult; Anti-Bacterial Agents; Diagnosis, Differential; Empyema, Pleural; Female; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Immunocompetence; Lemierre Syndrome; Meropenem; Pleural Effusion; Pneumonia; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Antibody Specificity; Antifungal Agents; Autoantibodies; Autoimmune Diseases; Ceftriaxone; Cephalosporins; Ciprofloxacin; Drug Substitution; Drug Therapy, Combination; Factor V; Factor V Deficiency; Fluoroquinolones; Humans; Levofloxacin; Male; Meropenem; Micafungin; Partial Thromboplastin Time; Pneumonia; Prothrombin Time

Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem.. Prospective randomized animal study.. Animal Research, University of Barcelona, Spain.. Thirty female pigs.. The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance.. We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004).. Our findings corroborate that amikacin and fosfomycin alone efficiently reduced P. aeruginosa in tracheal secretions, with negligible effects in pulmonary tissue. Combination of amikacin and fosfomycin with IV meropenem does not increase antipseudomonal pulmonary tissue activity, but it does reduce development of meropenem-resistant P. aeruginosa, in comparison with the sole use of IV meropenem. Our findings imply potential merits for preemptive use of nebulized antibiotics in order to reduce resistance to IV meropenem.

Topics: Administration, Inhalation; Administration, Intravenous; Amikacin; Animals; Anti-Bacterial Agents; Bacterial Load; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Lung; Meropenem; Nebulizers and Vaporizers; Pneumonia; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation; Swine; Trachea

The objective of this study was to develop a physiologically based pharmacokinetic model for meropenem using a retrograde approach, which could serve as a basis for prediction of the systemic and infection-site drug exposures in different populations and indications. We intended this model to be a useful tool to inform (local) pharmacokinetic-based optimal dosing of meropenem in different settings.. We developed a reduced physiologically based pharmacokinetic model with NONMEM software using a top-down approach. We used historical (previously published) data for model development and qualification. We used steady-state systemic and infection-site concentrations from 60 adult patients diagnosed with severe lung infection for model development and internal evaluation. The data included rich plasma and sparse epithelial lining fluid samples. We based the internal validation of the model on successful numerical convergence, adequate precision in parameter estimation, acceptable goodness-of-fit plot with no indication of bias, and acceptable performance of visual predictive checks. We performed external validation by fitting the model to independent data from five previously published studies: four studies in patients with pneumonia, with different grades of renal impairment, and one study in morbidly obese patients.. We successfully fitted a reduced physiologically based pharmacokinetic model with six compartments (arterial and venous pools, infection site [lungs], liver, kidneys and rest of the body) to the data and adequately estimated model parameters. We successfully qualified the model (internally and externally) using established methods. Estimated values for tissue-to-plasma partition coefficients were 0.2629 and 0.1946 for lungs and non-fat tissues (kidneys and liver), respectively. Estimated total clearance was 8.174 L/h for a typical patient with a glomerular filtration rate of 65 mL/min. Consistent with the known mechanism of meropenem elimination and previously published models, renal clearance accounted for 70% of total clearance. The model had good predictive performances on data from five different sources including populations with different characteristics with regard to body size, renal function and morbidity.. We successfully developed a physiologically based pharmacokinetic model for meropenem in adult patients to be used as a basis for prediction of concentrations in different groups of patients, and eventually for effective dose individualisation in different subgroups of the population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Datasets as Topic; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Humans; Infusions, Intravenous; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Models, Biological; Pneumonia; Renal Elimination; Tissue Distribution; Young Adult

Topics: Animals; Antibodies, Bispecific; Bacteremia; Immunotherapy; Meropenem; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Treatment Outcome

We present a case of a 55-year-old Filipino man who was transferred from another institution where he was recently diagnosed with Crohn's disease but not started on any immunosuppressants. He underwent laparoscopic cholecystectomy with T-tube placement a few weeks prior to admission. On workup, abdominal CT scan was unremarkable, but blood cultures on the third hospital day grew

Topics: Anti-Bacterial Agents; Bacteremia; Burkholderia cepacia; Burkholderia Infections; Drug Therapy, Combination; Humans; Male; Meropenem; Middle Aged; Nebulizers and Vaporizers; Pneumonia; Treatment Outcome

We report an unusual presentation of pulmonary embolism (PE) where a 58-year-old man first developed symptoms of community-acquired pneumonia. Despite antibiotic therapy, he remained unwell with rising inflammatory markers, general malaise and persistent cough. He developed stony dull percussion and absent breath sounds to his left mid to lower zones. Serial chest x-rays showed progression from lobar consolidation to a large loculated left-sided pleural collection. CT chest showed left-sided lung abscess, empyema and bronchopleural fistulation. Incidentally, the scan revealed acute left-sided PE and its distribution corresponded with the location of the left lung abscess and empyema. The sequence of events likely started with PE leading to infarction, cavitation, abscess formation and bronchopleural fistulation. This patient was managed with a 6-month course of rivaroxaban. After completing 2 weeks of intravenous meropenem, he was converted to 4-week course of oral co-amoxiclav and metronidazole and attained full recovery.

Topics: Abscess; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchial Fistula; Disease Progression; Drug Therapy, Combination; Humans; Infarction; Male; Meropenem; Metronidazole; Middle Aged; Pleural Diseases; Pneumonia; Pulmonary Embolism; Radiography, Thoracic; Rivaroxaban; Thienamycins; Treatment Outcome

The effect of biofilm formation on bacteraemic pneumonia caused by A. baumannii is unknown. We conducted a 4-year multi-center retrospective study to analyze 71 and 202 patients with A. baumannii bacteraemic pneumonia caused by biofilm-forming and non-biofilm-forming isolates, respectively. The clinical features and outcomes of patients were investigated. Biofilm formation was determined by a microtitre plate assay. The antimicrobial susceptibilities of biofilm-associated cells were assessed using the minimum biofilm eradication concentration (MBEC) assay. Whole-genome sequencing was conducted to identify biofilm-associated genes and their promoters. Quantitative reverse transcription polymerase chain reaction was performed to confirm the expression difference of biofilm-associated genes. There was no significant difference in the clinical characteristics or the outcomes between patients infected with biofilm-forming and non-biofilm-forming strains. Compared with non-biofilm-forming isolates, biofilm-forming isolates exhibited lower resistance to most antimicrobials tested, including imipenem, meropenem, ceftazidime, ciprofloxacin and gentamicin; however, the MBEC assay confirmed the increased antibiotic resistance of the biofilm-embedded bacteria. Biofilm-associated genes and their promoters were detected in most isolates, including the non-biofilm-forming strains. Biofilm-forming isolates showed higher levels of expression of the biofilm-associated genes than non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii isolates might not be associated with worse outcomes in patients with bacteraemic pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia; Retrospective Studies

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Haemophilus influenzae; Hospitals, Community; Humans; Japan; Male; Meropenem; Pneumonia; Providencia; Staphylococcus aureus; Streptococcus pneumoniae

Nosocomial pneumonia (NP) is a frequent complication among patients with intracerebral hemorrhage (ICH). However, there are currently no pharmacokinetic (PK) and pharmacodynamic (PD) data to guide meropenem dosing in these patients.. To investigate the PK/PD properties of meropenem in these patients and whether the usual dosing regimens of meropenem (2-hour infusion, 1 g, every 8 hours) was suitable.. A total of 11 patients with a diagnosis of ICH complicated with NP were selected in the emergency internal medicine and treated with a 1-g/2-hours extended infusion model. The plasma concentrations of meropenem were determined by high-performance liquid chromatography. PK parameters were estimated by plasma concentration versus time profile using WinNonlin software. The probability of target attainments (PTAs) of meropenem at different minimum inhibitory concentrations (MICs) based on percentage time that concentrations were above the minimum inhibitory concentration (%T>MIC) value were performed by Monte Carlo simulation.. The volume of distribution and total body clearance of meropenem were 55.55 L/kg and 22.89 L/h, respectively. Using 40%T>MIC, PTA was >90% at MICs ≤4 µg/mL. Using 80% or 100%T>MIC, PTA was >90% only at MICs ≤1 µg/mL.. The PK/PD profile of dosing regimens tested will assist in selecting the appropriate meropenem regimens for these patients. At a target of 40%T>MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤4 µg/mL. However, when a higher target (80% or 100%) is desired for difficult-to-treat infections, larger doses, prolonged infusions, shorter intervals, and/or combination therapy may be required.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cerebral Hemorrhage; Cross Infection; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Pneumonia; Thienamycins

In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring.. A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality.. Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis.. Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Cross Infection; Drug Monitoring; Female; Humans; Imipenem; Infant; Intensive Care Units; Male; Meropenem; Middle Aged; Piperacillin; Pneumonia; Prognosis; Tertiary Care Centers; Thienamycins; Urinary Tract Infections; Vancomycin; Young Adult

Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Humans; Iatrogenic Disease; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Tazobactam; Thienamycins; Tobramycin

Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis patients while others experienced severe outcomes.. We report a case of late incidental cystic fibrosis diagnosis in a young Caucasian man suffering from respiratory failure following infection due to AH1N1 influenza virus. The patient was admitted to our department with fever, cough, and dyspnea at rest unresponsive to antibiotics CONCLUSIONS: Late diagnosis of cystic fibrosis in uncommon. This report highlights the importance of early cystic fibrosis diagnosis to minimize risk of occurrence of potential life-threatening complications.

Topics: Anti-Bacterial Agents; Ceftazidime; Colistin; Cystic Fibrosis; Delayed Diagnosis; Drainage, Postural; Genetic Testing; Humans; Incidental Findings; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Meropenem; Pneumonia; Referral and Consultation; Sweat; Thienamycins; Tomography, X-Ray Computed; Young Adult

Inappropriate use of broad-spectrum antimicrobials affects adversely both the individual patient and the general public. The aim of the study was to identify patients at risk for excessively prolonged carbapenem treatment in the ICU as a target for antimicrobial stewardship interventions.. Case-control study in a network of 11 ICUs of a university hospital. Patients with uninterrupted meropenem therapy (MT) > 4 weeks were compared to controls. Controls were defined as patients who stayed on the ICU > 4 weeks and received meropenem for ≤ 2 weeks. Associations between case-control status and potential risk factors were determined in a multivariate logistic regression model.. Between 1. Surgical patients with peritonitis and patients with known colonization with MDR Gram-negative bacteria are at risk for excessively prolonged carbapenem therapy and represent an important target population for antimicrobial stewardship interventions.

Topics: Aged; Anti-Bacterial Agents; Case-Control Studies; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Length of Stay; Male; Mediastinitis; Meropenem; Middle Aged; Odds Ratio; Peritonitis; Pneumonia; Risk Factors; Thienamycins; Time Factors

Pseudallescheria boydii is a fungal organism known to affect immunocompromised patients. This organism is known to cause, in severe cases, invasive infection of various organs such as the central nervous, cardiovascular, and respiratory systems. We report an unusual case of pulmonary P. boydii pneumonia in an immunocompromised critically ill patient with a co-infection of Aspergillus fumigatus and Aspergillus terreus with ARDS. This case highlights the importance of a high index of suspicion for superimposed fungal infections in patients who are critically ill and immunocompromised. Uncommon fungal pathogens should be considered in the differential diagnosis of respiratory failure, especially if diagnostic markers such as galactomannan (from BAL and serum) or 1,3-beta-D-glucan are elevated. Further diagnostic interventions are warranted when insufficient clinical improvement is observed to prevent treatment failure and adverse outcomes.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Clarithromycin; Coinfection; Critical Illness; Extracorporeal Membrane Oxygenation; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Linezolid; Male; Mannans; Meropenem; Pneumonia; Pseudallescheria; Severe Acute Respiratory Syndrome; Thienamycins; Transplant Recipients; Voriconazole

Minocycline-based combination therapy has been suggested to be a possible choice for the treatment of infections caused by minocycline-susceptible Acinetobacter baumannii, but its use for the treatment of infections caused by minocycline-resistant A. baumannii is not well established. In this study, we compared the efficacy of minocycline-based combination therapy (with colistin, cefoperazone-sulbactam, or meropenem) to that of colistin in combination with meropenem for the treatment of minocycline-resistant A. baumannii infection. From 2006 to 2010, 191 (17.6%) of 1,083 A. baumannii complex isolates not susceptible to minocycline from the Taiwan Surveillance of Antimicrobial Resistance program were collected. Four representative A. baumannii isolates resistant to minocycline, amikacin, ampicillin-sulbactam, ceftazidime, ciprofloxacin, cefepime, gentamicin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam were selected on the basis of the diversity of their pulsotypes, collection years, health care setting origins, and geographic areas of origination. All four isolates had tetB and overexpressed adeABC, as revealed by quantitative reverse transcription-PCR. Among all minocycline-based regimens, only the combination with colistin produced a fractional inhibitory concentration index comparable to that achieved with meropenem combined with colistin. Minocycline (4 or 16 μg/ml) in combination with colistin (0.5 μg/ml) also synergistically killed minocycline-resistant isolates in time-kill studies. Minocycline (50 mg/kg of body weight) in combination with colistin (10 mg/kg) significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice compared to the results of monotherapy. However, minocycline (16 μg/ml)-based therapy was not effective at reducing biofilm-associated bacteria at 24 or 48 h when its effectiveness was compared to that of colistin (0.5 μg/ml) and meropenem (8 μg/ml). The clinical use of minocycline in combination with colistin for the treatment of minocycline-resistant A. baumannii may warrant further investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Biofilms; Cefepime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gentamicins; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Taiwan; Thienamycins

Meropenem plus levofloxacin treatment was shown to be a promising combination in our in vitro hollow fiber infection model. We strove to validate this finding in a murine Pseudomonas pneumonia model.. A dose-ranging study with meropenem and levofloxacin alone and in combination against Pseudomonas aeruginosa was performed in a granulocytopenic murine pneumonia model. Meropenem and levofloxacin were administered to partially humanize their pharmacokinetic profiles in mouse serum. Total and resistant bacterial populations were estimated after 24 hours of therapy. Pharmacokinetic profiling of both drugs was performed in plasma and epithelial lining fluid, using a population model.. Meropenem and levofloxacin penetrations into epithelial lining fluid were 39.3% and 64.3%, respectively. Both monotherapies demonstrated good exposure responses. An innovative combination-therapy analytic approach demonstrated that the combination was statistically significantly synergistic (α = 2.475), as was shown in the hollow fiber infection model. Bacterial resistant to levofloxacin and meropenem was seen in the control arm. Levofloxacin monotherapy selected for resistance to itself. No resistant subpopulations were observed in any combination therapy arm.. The combination of meropenem plus levofloxacin was synergistic, producing good bacterial kill and resistance suppression. Given the track record of safety of each agent, this combination may be worthy of clinical trial.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Levofloxacin; Meropenem; Mice; Microbial Sensitivity Tests; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

To investigate the pathogen distribution and drug resistance in coal workers' pneumoconiosis associated with pneumonia and to provide a scientific basis for early guidance for rational clinical application of antibacterial agents.. Seventy-six patients with coal workers' pneumoconiosis associated with pneumonia who were admitted to our hospital from June 2011 to June 2014 were enrolled as subjects. The sputum specimens were aseptically collected for bacterial culture and drug sensitivity tests.. In 245 sputum specimens collected from 76 patients, a total of 218 strains of pathogens, including 163 strains of Gram-negative bacilli (74.77%), 39 strains of Gram-positive cocci (17.89%), and 16 strains of fungi (7.34%) were isolated by bacteriological tests. The main Gram-negative bacilli had high rates of resistance to amoxicillin/clavulanic acid, ampicillin, cotrimoxazole, cefotaxime, and aztreonam, and were sensitive to amikacin, imipenem, and meropenem. The main Gram-positive cocci had high rates of resistance to penicillin, erythromycin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, and clindamycin, and were sensitive to vancomycin and teicoplanin.. The main pathogens in these patients with coal workers' pneumoconiosis associated with pneumonia are Gram-negative bacilli, which are highly resistant to common clinically used antibacterial agents. The pathogen distribution and drug resistance should be well understood, and the antibacterial agents should be rationally selected according to the results of drug sensitivity tests.

Topics: Anthracosis; Anti-Bacterial Agents; Coal Mining; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Occupational Exposure; Pneumonia; Thienamycins

The impact of antimicrobial treatment on the outcome of carbapenem nonsusceptible Klebsiella pneumoniae (CnsKP) infections needs to be elucidated. This nationwide, multicenter study was conducted to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality among patients with CnsKP infection in Taiwan.Patients with CnsKP infections from 11 medical centers and 4 regional hospitals in Taiwan were enrolled in 2013. Carbapenem nonsusceptibility was defined as a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. Predictors of 14-day mortality were determined using the Cox proportional regression model. The influence of infection severity on the impact of appropriate use of antimicrobials on 14-day mortality was determined using the Acute Physiology and Chronic Health Evaluation (APACHE) II score.Overall 14-day mortality was 31.8% (49/154). Unadjusted mortality for appropriate antimicrobial therapy was 23.1% (18/78 patients). Appropriate therapy was independently associated with reduced mortality (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.80; P = 0.007). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with higher APACHE II scores (HR for patients with scores >15 and ≤35, 0.46; 95% CI 0.23-0.92; and for those with scores >35, 0.14; 95% CI, 0.02-0.99).In conclusion, appropriate antimicrobial therapy significantly reduces 14-day mortality for CnsKP infections. Survival benefit is more notable among more severely ill patients.

Topics: Aged; Anti-Infective Agents; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Medication Therapy Management; Meropenem; Microbial Sensitivity Tests; Middle Aged; Outcome Assessment, Health Care; Pneumonia; Proportional Hazards Models; Severity of Illness Index; Taiwan; Thienamycins

Pseudomonas aeruginosa (P. aeruginosa) infections are associated with considerable morbidity and mortality in immunocompromised patients due to antibiotic resistance. Therefore, we investigated the efficacy of the anti-P. aeruginosa serotype O11 lipopolysaccharide monoclonal antibody Panobacumab in a clinically relevant murine model of neutropenia induced by cyclophosphamide and in combination with meropenem in susceptible and meropenem resistant P. aeruginosa induced pneumonia. We observed that P. aeruginosa induced pneumonia was dramatically increased in neutropenic mice compared to immunocompetent mice. First, Panobacumab significantly reduced lung inflammation and enhanced bacterial clearance from the lung of neutropenic host. Secondly, combination of Panobacumab and meropenem had an additive effect. Third, Panobacumab retained activity on a meropenem resistant P. aeruginosa strain. In conclusion, the present data established that Panobacumab contributes to the clearance of P. aeruginosa in neutropenic hosts as well as in combination with antibiotics in immunocompetent hosts. This suggests beneficial effects of co-treatment even in immunocompromised individuals, suffering most of the morbidity and mortality of P. aeruginosa infections.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Drug Resistance, Bacterial; Drug Synergism; Female; Lung; Meropenem; Mice; Mice, Inbred C57BL; Neutropenia; Pneumonia; Pseudomonas aeruginosa; Thienamycins

Treating patients admitted to critical care with severe pneumonia requires timely intervention with an effective antibiotic. This reduces the risk of dying of pneumonia and minimises complications associated with a prolonged stay in critical care.. To compare the cost-effectiveness of meropenem 1 g/8 h with piperacillin/tazobactam 4.5 g/8 h for treating pneumonia in UK critical care.. A Markov model was built to estimate lifetime costs and quality-adjusted life years (QALYs) of using meropenem versus piperacillin/tazobactam to treat severe pneumonia. Estimates of effectiveness, utility weights and costs were obtained from published sources. Probabilistic sensitivity analysis was conducted to address uncertainty in the model results.. Cost of treating a patient with severe pneumonia was estimated as £19,026 with meropenem and £19,978 with piperacillin/tazobactam, respectively. QALYs gained were 4.768 with meropenem and 4.654 with piperacillin/tazobactam. Probabilistic sensitivity analysis showed meropenem to be consistently less costly and more effective than piperacillin/tazobactam.. The additional efficacy of meropenem translates into more patients surviving critical care and leaving this high-cost service more quickly than if they had been treated with piperacillin/tazobactam. As meropenem is more effective and less expensive than piperacillin/tazobactam at treating patients with severe pneumonia, it is the dominant treatment option.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cost-Benefit Analysis; Critical Care; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Male; Markov Chains; Meropenem; Middle Aged; Models, Economic; Penicillanic Acid; Piperacillin; Pneumonia; Quality-Adjusted Life Years; Tazobactam; Thienamycins; Treatment Failure; United Kingdom

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Doripenem; Drug Resistance, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation; Rectum; Stenotrophomonas maltophilia; Thienamycins

Meropenem is a carbapenem with a broad spectrum of activity against beta-lactamase-producing organisms. Valproic acid is widely used in the treatment of generalized tonic-clonic and partial seizures. Concomitant administration of meropenem and valproic acid reportedly leads to a rapid decline in serum concentrations of valproic acid, which is sometimes associated with seizures.. This report describes an 85-year-old Chinese male inpatient who twice received concomitant administration of meropenem and valproic acid for the treatment of pneumonia and poststroke epilepsy, respectively. Rapid declines in valproic acid concentrations were observed both times after meropenem administration. No seizures occurred in the first treatment period; however, when the patient suffered pneumonia again 3 months later, the same concomitant therapy was prescribed, and seizures occurred. It is difficult to identify a single etiology of the seizures. Based on a score of 7 on the Naranjo adverse drug reaction probability scale, the seizures were considered to be probably related to the concomitant administration of meropenem and valproic acid.. Various factors make the effect of concomitant administration of meropenem and valproic acid unpredictable, even in the same patient. Caution should be used when administering meropenem and valproic acid concomitantly, especially in elderly patients with central nervous system disorders, even if the patient has had a successful prior experience with these 2 drugs. If concomitant administration is essential, very close serum concentration monitoring and clinical observation are necessary.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Anticonvulsants; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Humans; Male; Meropenem; Pneumonia; Seizures; Thienamycins; Treatment Outcome; Valproic Acid

Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units. A total of 61 episodes of VAP caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates were Carb-S and 31 were Col-S. Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.

Topics: Acinetobacter Infections; Analysis of Variance; Anti-Bacterial Agents; Chi-Square Distribution; Colistin; Drug Resistance, Microbial; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial; Retrospective Studies; Risk Factors; Thienamycins; Ventilators, Mechanical

A 55-year-old woman was diagnosed with pneumonia and was treated with meropenem; 5 days later she developed epileptic seizures. She had been treated with valproic acid for 16 years to control her epileptic seizures. Her serum valproic acid concentration was low during treatment with meropenem than previously recorded despite an increase of valproic dose. As soon as administration of meropenem was withdrawn, valproic acid concentration increased to previous levels and her seizures stopped. Meropenem decreases valproic acid concentration, and may promote the development of epileptic seizures in previously controlled epileptic patients. The acute lowering of serum valproate produced by meropenem probably precludes their concomitant use.

Topics: Anticonvulsants; Drug Interactions; Epilepsy; Female; Humans; Meropenem; Middle Aged; Pneumonia; Thienamycins; Valproic Acid

Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values. Serum and microdialysis samples were collected at 20-min intervals for at least 8 h following a single intravenous dose of 1 g of meropenem. The maximum free interstitial concentration (mean and standard deviation) of meropenem in infected lung tissue was 11.4 +/- 10.9 mg/liter, and that in serum was 47.3 +/- 21.0 mg/liter. The areas under the curve for infected lung tissue (36.2 +/- 17.9 mg. h/liter) and serum (95.4 +/- 46.6 mg. h/liter) revealed a significant difference. This technique enabled quasi-continuous tissue pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue of patients with pneumonia. The present data corroborate the use of meropenem in the treatment of lung infections caused by extracellular bacteria, demonstrating the excellent distribution profile for meropenem in the interstitial space of human pneumonic lung tissue.

Topics: Adult; Aged; Area Under Curve; Female; Half-Life; Humans; Injections, Intravenous; Lung; Male; Meropenem; Microdialysis; Middle Aged; Muscle, Skeletal; Pneumonia; Thienamycins

Abstract Sub-inhibitory concentrations of imipenem and meropenem were evaluated for their ability to induce morphological changes with six strains of Acinetobacter baumannii isolated from patients with nosocomial pneumonia. Three strains were susceptible and three were resistant to carbapenems. The strains were grown in the presence of 0 (controls), 0.25x, 0.5x and 1x the MIC of both carbapenems for 4 h, and then examined after Gram's stain. Cells > or = 3 microm in size (spheroplasts) were considered to be altered. Both carbapenems induced significant numbers of spheroplasts compared to controls. Imipenem had more effect against susceptible strains, while meropenem had a greater effect against resistant strains.

Topics: Acinetobacter baumannii; Carbapenems; Cross Infection; Histocytochemistry; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pneumonia; Thienamycins

Topics: Aged; Drug Resistance, Bacterial; Humans; Male; Meropenem; Middle Aged; Pneumonia; Thienamycins; Ventilators, Mechanical

We have carried out clinical studies on meropenem (MEPM, SM-7338), the results are summarized as follows. Treatment with MEPM was made in 13 cases of pediatric bacterial infections including 9 cases of pneumonia and 2 cases of colitis and 1 case each of purulent tonsillitis, and pharyngitis. Results obtained were excellent in 10 cases, good in 3 cases. No significant side effects due to the drug were observed in any cases, except in 1 case each of eosinophilia, elevated gamma-GTP, elevated total bilirubin and elevated GPT.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Liver; Male; Meropenem; Pneumonia; Thienamycins