OBJECTIVES: To determine whether currently used meropenem dosages in our hospital provide adequate serum concentrations. METHODS: Trough blood samples taken during the first meropenem concentration monitoring were included. For the evaluation of achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target, MIC of the pathogens defined by the European Committee on Antimicrobial Susceptibility testing was selected. RESULTS: Eighty three patients were enrolled. A large variability in meropenem trough serum concentrations was observed (median 34.3 mg/L, range < 1.0-146.1 mg/L). The lowest PK/PD target for susceptible pathogens (100% T > MIC) was achieved in 100% of patients on dialysis and continuous renal replacement therapy (CRRT) and in 91% non-RRT patients. For pathogens with intermediate susceptibility, 100% T > MIC was attained in all patients on CRRT and 96% on dialysis, only 74% non-RRT patients achieved this PK/PD target. Patients on RRT were more likely to achieve the highest PK/PD target 100% T > 5 × MIC, P < 0.05. Higher proportion of patients on RRT would also require meropenem dose reduction if upper limit 100% T > 10 × MIC was chosen, P < 0.05. CONCLUSIONS: Administration of a standard meropenem dose to critically ill patients leads to a large concentration variability. Thus, a personalised dosing regimen is crucial for the achievement of adequate meropenem exposure.

• Klíčová slova
• MIC, meropenem, pharmacokinetic/pharmacodynamic target, trough concentrations,
• MeSH
• antibakteriální látky * terapeutické užití   MeSH
• lidé MeSH
• meropenem MeSH
• mikrobiální testy citlivosti MeSH
• péče o pacienty v kritickém stavu * MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• meropenem MeSH

We present two case reports of drug interaction between valproic acid and meropenem. In comparison with expected population-kinetic based serum levels, we observed 90.8 and 93.5% decrease in valproic acid serum levels during concomitant administration with meropenem. If carbapenems need to be administered to valproic acid treated patient, other anticonvulsant addition seems to be the appropriate as most probably the valproic acid dose escalation would not be sufficient to achieve therapeutic serum concentration.

• Klíčová slova
• Drug interaction, Meropenem, Therapeutic drug monitoring, Valproic acid,
• MeSH
• antibakteriální látky škodlivé účinky   MeSH
• antikonvulziva škodlivé účinky   krev   MeSH
• kyselina valproová škodlivé účinky   krev   MeSH
• lékové interakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem MeSH
• thienamyciny škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antibakteriální látky MeSH
• antikonvulziva MeSH
• kyselina valproová MeSH
• meropenem MeSH
• thienamyciny MeSH

• MeSH
• bakteriální infekce farmakoterapie   MeSH
• dospělí MeSH
• gynekologická onemocnění farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem MeSH
• mladiství MeSH
• senioři MeSH
• thienamyciny terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• meropenem MeSH
• thienamyciny MeSH

Six strains of Acinetobacter baumannii out of eleven strains tested revealed a strong hydrophobic character. This was demonstrated by adherence of bacteria to xylene in the range of 90-94%. Changes in surface hydrophobicity of these strains were studied after treatment with meropenem at subinhibitory concentrations (sub-MICs) (1/4, 1/8, 1/16 or 1/32 of the MICs). All strains showed a reduced adherence to xylene after the action of meropenem at 1/4 or 1/16 of the MICs. Hydrophobicity of the treated bacteria was decreased to 1.3-70% (1/16 of the MICs) or to 12-86% (1/4 of the MICs), depending on the strain. A decrease in surface hydrophobicity of three strains was also observed after their exposure to meropenem at 1/8 of the MICs (to 18-71% of the control values). Meropenem at 1/32 of the MICs practically did not affect bacterial hydrophobic properties, with the exception of one strain.

• MeSH
• Acinetobacter účinky léků   patogenita   MeSH
• antibiotická rezistence MeSH
• bakteriální adheze účinky léků   MeSH
• meropenem MeSH
• mikrobiální testy citlivosti MeSH
• povrchové vlastnosti účinky léků   MeSH
• thienamyciny farmakologie   MeSH
• xyleny metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• meropenem MeSH
• thienamyciny MeSH
• xyleny MeSH

BACKGROUND: Meropenem dosing for septic critically patients is difficult due to pathophysiological changes associated with sepsis as well as supportive symptomatic therapies. A prospective single-center study assessed whether fluid retention alters meropenem pharmacokinetics and the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy. METHODS: Twenty-five septic ICU patients (19 m, 6f) aged 32-86 years with the mean APACHE II score of 20.2 (range 11-33), suffering mainly from perioperative intra-abdominal or respiratory infections and septic shock (n = 18), were investigated over three days after the start of extended 3-h i.v. infusions of meropenem q8h. Urinary creatinine clearance (CLcr) and cumulative fluid balance (CFB) were measured daily. Plasma meropenem was measured, and Bayesian estimates of PK parameters were calculated. RESULTS: Eleven patients (9 with peritonitis) were classified as fluid overload (FO) based on a positive day 1 CFB of more than 10% body weight. Compared to NoFO patients (n = 14, 11 with pneumonia), the FO patients had a lower meropenem clearance (CLme 8.5 ± 3.2 vs 11.5 ± 3.5 L/h), higher volume of distribution (V1 14.9 ± 3.5 vs 13.5 ± 4.1 L) and longer half-life (t1/2 1.4 ± 0.63 vs 0.92 ± 0.54 h) (p < 0.05). Over three days, the CFB of the FO patients decreased (11.7 ± 3.3 vs 6.7 ± 4.3 L, p < 0.05) and the PK parameters reached the values comparable with NoFO patients (CLme 12.4 ± 3.8 vs 11.5 ± 2.0 L/h, V1 13.7 ± 2.0 vs 14.0 ± 5.1 L, t1/2 0.81 ± 0.23 vs 0.87 ± 0.40 h). The CLcr and Cockroft-Gault CLcr were stable in time and comparable. The correlation with CLme was weak to moderate (CLcr, day 3 CGCLcr) or absent (day 1 and 2 CGCLcr). Dosing with 2 g meropenem q8h ensured adequate concentrations to treat infections with sensitive pathogens (MIC 2 mg/L). The proportion of pre-dose concentrations exceeding the MIC 8 mg/L and the fraction time with a target-exceeding concentration were higher in the FO group (day 1-3 f Cmin > MIC: 67 vs 27%, p < 0.001; day 1%f T > MIC: 79 ± 17 vs 58 ± 17, p < 0.05). CONCLUSIONS: These findings emphasize the importance of TDM and a cautious approach to augmented maintenance dosing of meropenem to patients with FO infected with less susceptible pathogens, if guided by population covariate relationships between CLme and creatinine clearance.

• Klíčová slova
• Critically ill patients, Fluid therapy, Meropenem, Pharmacodynamics, Pharmacokinetics, Sepsis,
• MeSH
• antibakteriální látky metabolismus   farmakokinetika   MeSH
• APACHE MeSH
• Bayesova věta MeSH
• dospělí MeSH
• farmakokinetika * MeSH
• jednotky intenzivní péče organizace a řízení   statistika a číselné údaje   MeSH
• kritický stav terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem metabolismus   farmakokinetika   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sepse farmakoterapie   patofyziologie   MeSH
• vodní a elektrolytová rovnováha účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antibakteriální látky MeSH
• meropenem MeSH

Carbapenem resistance observed in Klebsiella pneumoniae strains limits treatment options. Therefore, use of antibiotics combined with bioactive compounds may be an important strategy to control K. pneumoniae. The purpose of this study was to evaluate the activity of combination of carvacrol and meropenem on carbapenem-resistant K. pneumoniae (CRKP) strains. The presence of blaOXA-48 carbapenemase in all 25 CRKP strains was identified using the PCR technique. The combination of carvacrol and meropenem was tested for antimicrobial activity on CRKP strains. The minimum inhibitory concentrations of carvacrol and meropenem were detected within a range of 32-128 µg/mL using the broth microdilution method. Synergy between carvacrol and meropenem was observed on 8 of the 25 CRKP strains by checkerboard assay (FICI = 0.5) and confirmed by time-kill assay. According to the live-dead test results, the viability percentage of the cells exposed to synergistic combination was 35.47% at the end of 24 h. The membrane damage caused by the synergistic combination was spectrophotometrically measured (A = 0.21) and further confirmed by SEM analysis. According to the MTT assay, both carvacrol and meropenem did not show any statistically significant cytotoxic effect on Vero cells (p > 0.05). In conclusion, the results suggest that carvacrol and meropenem can act synergistically to inhibit the growth of CRKP.

• MeSH
• antibakteriální látky farmakologie   MeSH
• beta-laktamasy * genetika   MeSH
• Cercopithecus aethiops MeSH
• cymeny MeSH
• karbapenemy farmakologie   MeSH
• Klebsiella pneumoniae * MeSH
• meropenem farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• synergismus léků MeSH
• Vero buňky MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• beta-laktamasy * MeSH
• carvacrol MeSH Prohlížeč
• cymeny MeSH
• karbapenemy MeSH
• meropenem MeSH

OBJECTIVES: The objective of this study was to develop a population pharmacokinetic model of meropenem in a heterogeneous population of patients with a serious bacterial infection in order to propose dosing optimisation leading to improved achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target. METHODS: A total of 174 meropenem serum levels obtained from 144 patients during therapeutic drug monitoring were analysed using a non-linear mixed-effects modelling approach and Monte Carlo simulation was then used to compare various dosing regimens in order to optimise PK/PD target attainment. RESULTS: The meropenem volume of distribution of the patient population was 54.95 L, while clearance started at 3.27 L/hour and increased by 0.91 L/hour with each 1 mL/s/1.73 m2 of estimated glomerular filtration rate. Meropenem clearance was also 0.31 L/hour higher in postoperative patients with central nervous system infection. Meropenem administration by continuous infusion showed a significantly higher probability of attaining the PK/PD target than a standard 30 min infusion (95.3% vs 49.5%). CONCLUSIONS: A daily meropenem dose of 3 g, 6 g and 10.5 g administered by continuous infusion was shown to be accurate for patients with moderate to severe renal impairment, normal renal function to mild renal impairment and augmented renal clearance, respectively.

• Klíčová slova
• administration, intravenous, critical care, drug monitoring, pharmacy service, hospital, practice guideline,
• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• bakteriální infekce * farmakoterapie   MeSH
• biologické modely * MeSH
• dospělí MeSH
• intravenózní infuze MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem * farmakokinetika   aplikace a dávkování   MeSH
• metoda Monte Carlo MeSH
• monitorování léčiv metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky * MeSH
• meropenem * MeSH

BACKGROUND: Nosocomial pneumonia is commonly associated with antimicrobial-resistant Gram-negative pathogens. We aimed to assess the efficacy and safety of ceftazidime-avibactam in patients with nosocomial pneumonia, including ventilator-associated pneumonia, compared with meropenem in a multinational, phase 3, double-blind, non-inferiority trial (REPROVE). METHODS: Adults with nosocomial pneumonia (including ventilator-associated pneumonia), enrolled at 136 centres in 23 countries, were randomly assigned (1:1) to 2000 mg ceftazidime and 500 mg avibactam (by 2 h intravenous infusion every 8 h) or 1000 mg meropenem (by 30-min intravenous infusion every 8 h) for 7-14 days; regimens were adjusted for renal function. Computer-generated randomisation codes were stratified by infection type and geographical region with a block size of four. Participants and investigators were masked to treatment assignment. The primary endpoint was clinical cure at the test-of-cure visit (21-25 days after randomisation). Non-inferiority was concluded if the lower limit of the two-sided 95% CI for the treatment difference was greater than -12·5% in the coprimary clinically modified intention-to-treat and clinically evaluable populations. This trial is registered with ClinicalTrials.gov (NCT01808092) and EudraCT (2012-004006-96). FINDINGS: Between April 13, 2013, and Dec 11, 2015, 879 patients were randomly assigned. 808 patients were included in the safety population, 726 were included in the clinically modified intention-to-treat population, and 527 were included in the clinically evaluable population. Predominant Gram-negative baseline pathogens in the microbiologically modified intention-to-treat population (n=355) were Klebsiella pneumoniae (37%) and Pseudomonas aeruginosa (30%); 28% were ceftazidime-non-susceptible. In the clinically modified intention-to-treat population, 245 (68·8%) of 356 patients in the ceftazidime-avibactam group were clinically cured, compared with 270 (73·0%) of 370 patients in the meropenem group (difference -4·2% [95% CI -10·8 to 2·5]). In the clinically evaluable population, 199 (77·4%) of 257 participants were clinically cured in the ceftazidime-avibactam group, compared with 211 (78·1%) of 270 in the meropenem group (difference -0·7% [95% CI -7·9 to 6·4]). Adverse events occurred in 302 (75%) of 405 patients in the ceftazidime-avibactam group versus 299 (74%) of 403 in the meropenem group (safety population), and were mostly mild or moderate in intensity and unrelated to study treatment. Serious adverse events occurred in 75 (19%) patients in the ceftazidime-avibactam group and 54 (13%) patients in the meropenem group. Four serious adverse events (all in the ceftazidime-avibactam group) were judged to be treatment related. INTERPRETATION: Ceftazidime-avibactam was non-inferior to meropenem in the treatment of nosocomial pneumonia. These results support a role for ceftazidime-avibactam as a potential alternative to carbapenems in patients with nosocomial pneumonia (including ventilator-associated pneumonia) caused by Gram-negative pathogens. FUNDING: AstraZeneca.

• MeSH
• antibakteriální látky terapeutické užití   MeSH
• azabicyklické sloučeniny terapeutické užití   MeSH
• ceftazidim terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fixní kombinace léků MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem terapeutické užití   MeSH
• senioři MeSH
• ventilátorová pneumonie farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• avibactam, ceftazidime drug combination MeSH Prohlížeč
• azabicyklické sloučeniny MeSH
• ceftazidim MeSH
• fixní kombinace léků MeSH
• meropenem MeSH

OBJECTIVES: In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated. METHODS: Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7-14 days after the end of therapy) in the microbiological ITT (mITT) population. RESULTS: The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: -4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: -18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: -4.51 to 19.38], respectively, were also comparable. CONCLUSIONS: In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.

• MeSH
• antibakteriální látky * terapeutické užití   MeSH
• bakteriální pneumonie * farmakoterapie   MeSH
• cefalosporiny terapeutické užití   MeSH
• lidé MeSH
• mechanické ventilátory MeSH
• meropenem terapeutické užití   MeSH
• mikrobiální testy citlivosti MeSH
• nemocnice MeSH
• prospektivní studie MeSH
• Pseudomonas aeruginosa MeSH
• tazobaktam terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antibakteriální látky * MeSH
• cefalosporiny MeSH
• ceftolozane MeSH Prohlížeč
• meropenem MeSH
• tazobaktam MeSH

A comparison of carbapenem molecules for the detection of carbapenemase-producing bacteria by MALDI-TOF MS showed that imipenem exhibited higher sensitivity (97%) and specificity (100%) scores for Pseudomonas aeruginosa than meropenem. However, meropenem was more efficient (98% sensitivity and 100% specificity) against Enterobacteriaceae.

• Klíčová slova
• Carbapenems, Enterobacteriaceae, GES, IMP, Pseudomonas aeruginosa, VIM,
• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální proteiny analýza   metabolismus   MeSH
• bakteriologické techniky metody   MeSH
• beta-laktamasy analýza   metabolismus   MeSH
• Enterobacteriaceae účinky léků   enzymologie   MeSH
• imipenem farmakologie   MeSH
• karbapenemy farmakologie   MeSH
• meropenem MeSH
• mikrobiální testy citlivosti MeSH
• Pseudomonas aeruginosa účinky léků   enzymologie   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   MeSH
• thienamyciny farmakokinetika   MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• bakteriální proteiny MeSH
• beta-laktamasy MeSH
• carbapenemase MeSH Prohlížeč
• imipenem MeSH
• karbapenemy MeSH
• meropenem MeSH
• thienamyciny MeSH