Plasma and tissue concentrations of 2 g prophylactic cefazolin prior to lower extremity surgery.

Surgical site infections (SSIs) are among the most clinically relevant complications and the use of prophylactic cefazolin is common practice. However, the knowledge about the pharmacological aspects of prophylactic cefazolin in the lower extremities remains limited. In this prospective cohort, a sub-study of the WIFI-2 randomized controlled trial, adults between 18 and 75 years of age who were scheduled for implant removal below the level of the knee and randomized for cefazolin, was included.

Fusariosis in patients with hematological malignancies: Two case reports.

Immunosuppressed patients with hematological malignancies are at risk for invasive fungal infections (IFI), including infections with species (spp.), which are increasingly reported. Particularly at risk are patients with acute myeloid leukemia (AML) treated with high-dose cytarabine as remission-induction therapy.

Benzylpenicillin concentrations in umbilical cord blood and plasma of premature neonates following intrapartum doses for group B streptococcal prophylaxis.

Background And Method: Dutch obstetrics guideline suggest an initial maternal benzylpenicillin dose of 2,000,000 IU followed by 1,000,000 IU every 4 h for group-B-streptococci (GBS) prophylaxis. The objective of this study was to evaluate whether concentrations of benzylpenicillin reached concentrations above the minimal inhibitory concentrations (MIC) in umbilical cord blood (UCB) and neonatal plasma following the Dutch guideline.

Results: Forty-six neonates were included.

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia.

Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment. Data were collected in the PharmaCool prospective observational multicenter study.

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review.

Gentamicin is an aminoglycoside antibiotic with a small therapeutic window that is currently used primarily as part of short-term empirical combination therapy. Gentamicin dosing schemes still need refinement, especially for subpopulations where pharmacokinetics can differ from pharmacokinetics in the general adult population: obese patients, critically ill patients, paediatric patients, neonates, elderly patients and patients on dialysis. This review summarizes the clinical pharmacokinetics of gentamicin in these patient populations and the consequences for optimal dosing of gentamicin for infections caused by Gram-negative bacteria, highlighting new insights from the last 10 years.

Impact of a vancomycin loading dose on the achievement of target vancomycin exposure in the first 24 h and on the accompanying risk of nephrotoxicity in critically ill patients.

Background: The advocated pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin, AUC/MIC ≥ 400 mg·h/L, may not be reached with a conventional fixed starting dose of 1000 mg in critically ill patients, but increasing the dose may cause nephrotoxicity.

Objectives: To evaluate the effect of a weight-based loading dose of 25 mg/kg vancomycin on PK/PD target attainment in the first 24 h (AUC0-24) in critically ill patients and to evaluate whether this increases the risk of acute kidney injury (AKI).

Patients And Methods: A prospective observational before/after study was performed in ICU patients, comparing the percentage of vancomycin courses with AUC0-24 ≥ 400 mg·h/L and the incidence of AKI, defined as worsening of the risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE) score.

Population Pharmacokinetics and Probability of Target Attainment of Different Dosing Regimens of Ceftazidime in Critically Ill Patients with a Proven or Suspected Infection.

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement.

Correction to: Neonatal bacterial meningitis versus ventriculitis: a cohort-based overview of clinical characteristics, microbiology and imaging.

This article originally published with all author names incorrectly listed. All author names have now been transposed and appear correctly above.

Neonatal bacterial meningitis versus ventriculitis: a cohort-based overview of clinical characteristics, microbiology and imaging.

Central nervous system (CNS) infections are potentially life threatening in neonates and can lead to the ill-defined diagnosis of ventriculitis. With this study we aimed to explore and describe ventriculitis regarding clinical, microbiological and ultrasonographic characteristics. We performed a retrospective cohort study including all neonates with a culture-proven CNS infection admitted to our tertiary NICU over a 12-year period (2004-2016).

Microbiological profile of nosocomial infections following cardiac arrest: Insights from the targeted temperature management (TTM) trial.

Aims: Infectious complications frequently occur in intensive care unit patients admitted after out-of-hospital cardiac arrest. There is debate on the effects of temperature management on the incidence of infections, as well as on the efficacy and choice of antibiotic prophylaxis. In this substudy of the targeted temperature management (TTM) trial, we describe the microbiological profile of infectious complications in patients with cardiac arrest and examined the impact of TTM at 33 °C compared to TTM at 36 °C.

Population Pharmacokinetics of Ganciclovir in Critically Ill Patients.

Background: The pharmacokinetic (PK) data of ganciclovir (GCV), a first-line antiviral treatment for cytomegalovirus infections, in critically ill patients are limited. This study aimed at characterizing GCV population PK and interindividual variability (IIV) in intensive care unit (ICU) patients. Secondary objectives were to identify patient characteristics responsible for IIV and simulate GCV exposure for different dosing regimens.

Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study.

Background: Invasive pulmonary aspergillosis typically occurs in an immunocompromised host. For almost a century, influenza has been known to set up for bacterial superinfections, but recently patients with severe influenza were also reported to develop invasive pulmonary aspergillosis. We aimed to measure the incidence of invasive pulmonary aspergillosis over several seasons in patients with influenza pneumonia in the intensive care unit (ICU) and to assess whether influenza was an independent risk factor for invasive pulmonary aspergillosis.

Predictive performance of a gentamicin population pharmacokinetic model in two western populations of critically ill patients.

Unlabelled: External validation of population pharmacokinetic (PK) models is warranted before they can be clinically applied to aid in antibiotic dose selection. The primary objective of this study was to assess the predictive performance of a gentamicin population PK model in intensive care unit (ICU) patients in two independent western populations of critically ill patients.

Methods: Data were collected from the ICU where the model was developed (Academic Medical Centre, Amsterdam [AMC]) and from the Centre Hospitalier Universitaire de Nîmes (CHU Nîmes).

Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study.

Objective: Infections with multidrug-resistant microorganisms are associated with increased hospitalization, medication costs and mortality. Based on our fecal microbiota transplantation (FMT) experience for Clostridium difficile infection, we treated 15 patients carrying ESBL-producing Enterobacteriaceae (ESBL-EB) with FMT. Seven patients underwent a second FMT after 4 weeks when ESBL-EB remained, amounting to a total number of 22 transplants.

Optimization of therapy against Pseudomonas aeruginosa with ceftazidime and meropenem using chemostats as model for infections.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause life-threatening infections in patients admitted to intensive care units. Resistance rapidly develops against two drugs of choice: ceftazidime and meropenem. Several therapeutic protocols were compared for reduction in viable cells and limiting development of resistance.

Therapeutic Drug Monitoring of Gentamicin Peak Concentrations in Critically Ill Patients.

Background: Adequate gentamicin peak concentrations (Cmax) are important for optimal clinical efficacy. Within a critically ill patient, substantial variability in Cmax can occur over time, hampering the usefulness of therapeutic drug monitoring (TDM). The aim of this study was to evaluate the effect of gentamicin dosing based on Cmax after the first dose on gentamicin target attainment in critically ill patients.

Determinants of gentamicin concentrations in critically ill patients: a population pharmacokinetic analysis.

When treating critically ill patients with gentamicin for severe infection, peak concentrations (C) determine clinical efficacy and trough concentrations (C) determine toxicity. Despite administration of body weight-standardised starting doses, a wide range of C is generally observed. Furthermore, in therapeutic drug monitoring, several measures of renal function are used to predict appropriate C and gentamicin dosing intervals, but the most accurate predictor is not known.

Population Pharmacokinetics and Dosing Considerations for Gentamicin in Newborns with Suspected or Proven Sepsis Caused by Gram-Negative Bacteria.

The aim of this study was to describe the population pharmacokinetics (PK) of gentamicin in neonates with suspected or proven Gram-negative sepsis and determine the optimal dosage regimen in relation to the bacterial MICs found in this population. Data were prospectively collected between October 2012 and January 2013 in the Neonatal Intensive Care Unit (NICU) at the Academic Medical Center (AMC), Amsterdam, The Netherlands. A single nonlinear mixed-effects regression analysis (NONMEM) was performed to describe the population PK of gentamicin.

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.].

Incidence, risk factors, and the impact of allograft pyelonephritis on renal allograft function.

Background: The impact of allograft pyelonephritis (AGPN) on renal allograft function is controversial. In this study, we evaluated the incidence, risk factors, and the impact of AGPN on renal allograft function.

Methods: Retrospective cohort study in adult renal allograft recipients with 1-year follow-up after transplantation (Tx).

The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study.

Background: The international guidelines recommend the administration of trimethoprim-sulfamethoxazole (TMP-SMX) as Pneumocystis jiroveci pneumonia (PJP) prophylaxis for six months after transplantation. The aim of this study is to evaluate the influence of TMP-SMX prophylaxis on the occurrence of asymptomatic bacteriuria (ASB) and urinary tract infections (UTIs) as cystitis and allograft pyelonephritis (AGPN) and its impact on the antimicrobial resistance pattern of causative microorganisms.

Methods: We have conducted a retrospective before-after study in adult renal allograft recipients with one year follow-up after transplantation.

Development of Antibiotic Resistance during Simulated Treatment of Pseudomonas aeruginosa in Chemostats.

During treatment of infections with antibiotics in critically ill patients in the intensive care resistance often develops. This study aims to establish whether under those conditions this resistance can develop de novo or that genetic exchange between bacteria is by necessity involved. Chemostat cultures of Pseudomonas aeruginosa were exposed to treatment regimes with ceftazidime and meropenem that simulated conditions expected in patient plasma.