[S2k guidelines of the PEG on calculated parenteral initial treatment of bacterial diseases in adults : Focussed summary and supplementary information on antibiotic treatment of critically ill patients]. / S2k-Leitlinie der PEG zur kalkulierten parenteralen Initialtherapie bakterieller Erkrankungen bei Erwachsenen : Fokussierte Zusammenfassung und ergänzende Informationen zur Antibiotikatherapie kritisch kranker Patienten.

In January 2018 the recent revision of the S2k guidelines on calculated parenteral initial treatment of bacterial diseases in adults-update 2018 (Editor: Paul Ehrlich Society for Chemotherapy, PEG) was realized. It is a helpful tool for the complex infectious disease setting in an intensive care unit. The present summary of the guidelines focuses on the topics of anti-infective agents, including new substances, pharmacokinetics and pharmacodynamics as well as on microbiology, resistance development and recommendations for calculated drug therapy in septic patients. As in past revisions the recent resistance situation and results of new clinical studies are considered and anti-infective agents are summarized in a table.

[Adequate anti-infective treatment : Importance of individual dosing and application]. / Adäquate Antiinfektivatherapie : Bedeutung der individuellen Dosierung und Applikation.

Sepsis-induced changes in pharmacokinetic parameters are a well-known problem in intensive care medicine. Dosing of antibiotics in this setting is therefore challenging. Alterations to the substance-specific kinetics of anti-infective substances have an effect on the distribution and excretion processes in the body. Increased clearance and an increased distribution volume (Vd) and particularly compromized organ function with reduced antibiotic elimination are often encountered in patients with sepsis. Renal replacement treatment, which is frequently used in intensive care medicine, represents a substantial intervention in this system. Current international guidelines recommend individualized dosing strategies and adaptation of doses according to measured serum levels and pharmacokinetic/pharmacodynamic (PK/PD) parameters as concepts to optimize anti-infective therapy in the critically ill. Likewise, the recommendation to adjust the administration form of beta-lactam antibiotics to prolonged or continuous infusion can be found increasingly more often in the literature. This article reviews the background of the individual dosing in intensive care patients and their applicability to the clinical routine.

[Therapeutic drug monitoring and individual dosing of antibiotics during sepsis : Modern or just "trendy"?] / Therapeutisches Drug Monitoring und individualisierte Dosierung von Antibiotika bei der Sepsis : Modern oder nur "modisch"?

Pharmacokinetic variability of anti-infective drugs due to pathophysiological changes by severe sepsis and septic shock is a well-known problem for critically ill patients resulting in suboptimal serum and most likely tissue concentrations of these agents.To cover a wide range of potential pathogens, high concentrations of broad spectrum anti-infectives have to reach the site of infection. Microbiological susceptibility testing (susceptible, intermediate, resistant) don't take the pharmacokinetic variability into account and are based on data generated by non-critically ill patients. But inter-patient variability in distribution and elimination of anti-infective drugs in ICU patients is extremely high and also highly unpredictable. Drug clearance of mainly renally eliminated drugs and thus the required dose can differ up to 10-fold due to the variability in renal function in patients with severe infections. To assure a timely and adequate anti-infective regime, individual dosing and therapeutic drug monitoring (TDM) seem to be appropriate tools in the setting of pathophysiological changes in pharmacokinetics (PK) and pharmakodynamics (PD) due to severe sepsis. In the case of known minimal inhibitory concentration, PK/PD indices (time or peak concentration dependent activity) and measured serum level can provide an optimal target concentration for the individual drug and patient.Modern anti-infective management for ICU patients includes more than the choice of drug and prompt application. Individual dosing, optimized prolonged infusion time and TDM give way to new and promising opportunities in infection control.

[Administering drugs to infants, children, and adolescents]. / Arzneimittelanwendung bei Kindern und Jugendlichen.

In many cases, pharmaceutical manufacturers do not embark on lenghty licencing procedures for pediatric medications. Therefore, formulations and dosages suitable for children are often not available, and even medications that have been approved for pediatric use sometimes lack the information and tools required for correct usage. Therefore, choosing a suitable medication that allows for individual dosing, taking into account physiological peculiarities, providing appropriate tools and comprehensive information for parents and/or nursing staff is vital to the success of drug treatments in pediatric patients.

Adverse effects in a newborn infant breast-fed by a mother treated with doxepin.

OBJECTIVE: To report adverse effects in a newborn infant whose mother had been treated with doxepin during pregnancy and while breast-feeding. CASE SUMMARY: The nine-day-old white boy was admitted because of poor sucking and swallowing, with muscle hypotonia and vomiting. He was drowsy and had lost 150 g. At the time of admission, he was breast-fed by his mother who was being treated with doxepin 35 mg/d. Samples of plasma and breast milk were taken and analyzed by HPLC and fluorescence polarization immunoassay. The amount of doxepin and N-desmethyldoxepin (DDP) ingested via breast-feeding was approximately 10-20 micrograms/kg/d (i.e., only 2.5% of the weight-adjusted dose of the mother). Doxepin was detectable in small amounts in the infant's plasma (approximately 10 micrograms/L); DDP was below the lower limit of detection of 10 micrograms/L. All adverse effects subsided within 48 hours after breast-feeding was stopped. DISCUSSION: Despite the small doses of doxepin and its active metabolite ingested by breast-fed babies, there is a risk of accumulation and resultant adverse effects. In newborns, the metabolic activity is considerably decreased and may be further reduced by hyperbilirubinemia. CONCLUSIONS: Available data suggest that women treated with doxepin should breast-feed their infants with great caution, if at all, although much larger databases are needed to confirm this.

Comparison of phenytoin serum concentrations in premature neonates following intravenous and oral administration.

OBJECTIVE: To compare the serum concentrations attained following intravenous and oral administration of phenytoin in premature neonates. DESIGN: A prospective, uncontrolled study was conducted over 6 years. Phenhydan concentrate for infusion (Desitin, Hamburg, Germany) was used for intravenous infusion, and Epanutin suspension (Parke-Davis, Freiburg, Germany) was used for oral therapy. Blood samples were analyzed by using a fluorescence polarization immunoassay analyzer TDx model by Abbott Laboratories. SETTING: A university-affiliated district hospital. PARTICIPANTS: Twenty premature neonates who were administered intravenous and/or oral phenytoin between February 1991 and February 1997. MAIN OUTCOME MEASURES: Serum phenytoin concentrations on intravenous and oral phenytoin. RESULTS: Nine patients received intravenous (group A) and 15 patients received oral (group B) therapy. Mean +/- SD postnatal age (41 +/- 8.7 vs. 48 +/- 17 d; p = 0.03) and actual body weight (1.56 +/- 0.38 vs. 1.88 +/- 0.75 kg; p = 0.02) were slightly higher in group B. There were no significant differences between the groups in mean +/- SD gestational age (26.1 +/- 1.37 vs. 26.9 +/- 3.30 wk), 5-minute Apgar score (8.7 +/- 1.11 vs. 7.7 +/- 2.26), daily dosage (8.1 +/- 3.86 vs. 8.1 +/- 4.21 mg/kg/d), and phenytoin serum concentration (8.7 +/- 7.36 vs. 9.6 +/- 5.83 micrograms/mL). CONCLUSIONS: Contrary to data in the current literature, reliable serum concentrations in premature neonates were achieved by oral administration of phenytoin suspension. Oral therapy offers a number of advantages and considerably reduces the cost of therapy. Due to substantial variations in phenytoin pharmacokinetics in neonates, close monitoring of serum concentrations is required. Further investigation is required to confirm these results, especially in neonates younger than 20 days' postnatal age and those receiving products other than Epanutin.