Yoshiro Hayashi

Country-to-Country Transfer of Patients and the Risk of Multi-Resistant Bacterial Infection

Management of patients with a history of healthcare contact in multiple countries is now a reality for many clinicians. Leisure tourism, the burgeoning industry of medical tourism, military conflict, natural disasters, and changing patterns of human migration may all contribute to this emerging epidemiological trend. Such individuals may be both vectors and victims of healthcare-associated infection with multiresistant bacteria. Current literature describes intercountry transfer of multiresistant Acinetobacter spp and Klebsiella pneumoniae (including Klebsiella pneumoniae carbapenemase- and New Delhi metallo-β-lactamase-producing strains), methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and hypervirulent Clostridium difficile. Introduction of such organisms to new locations has led to their dissemination within hospitals. Healthcare institutions should have sound infection prevention strategies to mitigate the risk of dissemination of multiresistant organisms from patients who have been admitted to hospitals in other countries. Clinicians may also need to individualize empiric prescribing patterns to reflect the risk of multiresistant organisms in these patients.

Toward Improved Surveillance: The Impact of Ventilator-Associated Complications on Length of Stay and Antibiotic Use in Patients in Intensive Care Units

BACKGROUND Hospitals and quality improvement agencies are vigorously focusing on reducing rates of hospital-acquired infection. Ventilator-associated pneumonia (VAP) is notoriously difficult to diagnose and surveillance is thwarted by the subjectivity of many components of the surveillance definition. Alternative surveillance strategies are needed. Ventilator-associated complications (VAC) is a simple, objective measure of respiratory deterioration. METHODS VAC is defined by increases in fraction of inspired oxygen (FiO(2)) by ≥ 15% or positive end-expiratory pressure (PEEP) by ≥ 2.5 cm H(2)O lasting ≥ 2 days after stable or decreasing FiO(2) or PEEP lasting ≥ 2 days. We retrospectively assessed patients on mechanical ventilation for ≥ 48 hours in our study intensive care unit (ICU) using electronic medical record data. We analyzed the association between VAC and clinical diagnoses, ICU length of stay, duration of mechanical ventilation, antibiotic use, and mortality. RESULTS We assessed 153 patients with VAC and 390 without VAC. VAC events were associated with significantly increased ICU length of stay, duration of mechanical ventilation, and consumption of broad-spectrum antibiotics but not with longer hospital stays or ICU mortality. CONCLUSIONS Surveillance for VAP is subjective and labor intensive. VAC is an objective measure which can be readily obtained from electronic records. It is associated with adverse outcomes and increased broad-spectrum antibiotic usage. VAC may be a useful surveillance tool. The utility of VAC prevention bundles merits assessment.

Carbapenem Resistance in Klebsiella pneumoniae Due to the New Delhi Metallo-β-lactamase

Carbapenem resistance in Klebsiella pneumoniae is most notably due to the K. pneumoniae carbapenemase (KPC) β-lactamase. In this report, we describe the occurrence of a newly described mechanism of carbapenem resistance, the NDM-1 β-lactamase, in a patient who received medical attention (but was not hospitalized) in India.

Strategies for Reduction in Duration of Antibiotic Use in Hospitalized Patients

There is a global crisis of antibiotic resistance in part because of the collateral damage of antibiotic use. Reduction in antibiotic consumption is clearly important to minimize this problem. Limiting treatment duration may be the most clinically palatable means of reducing antibiotic consumption. Antimicrobial stewardship programs play an important role in this process. Their effectiveness may be increased by drawing on evidence from randomized controlled trials regarding optimal antibiotic duration. However, in most clinical scenarios, the recommended duration of therapy in published guidelines is based on expert opinion. Biological markers, such as procalcitonin, have been shown to reduce antimicrobial consumption with no adverse outcome in 11 randomized controlled trials. Although procalcitonin may not be the perfect biomarker, the concept of procalcitonin-guided antibiotic discontinuation after clinical stabilization, in conjunction with antimicrobial stewardship programs, appears to be ready for introduction into clinical practice.

Pharmacokinetic evaluation of piperacillin-tazobactam

Importance of the field: Piperacillin-tazobactam is a frequently prescribed intravenous antibiotic for moderate to severe infections used in hospital settings because of its broad activity against many pathogenic bacteria including Pseudomonas aeruginosa. However, its pharmacokinetics (PK) can be significantly altered in a variety of states. Areas covered in this review: This article provides a comprehensive and critical review of the PK of piperacillin-tazobactam in different patient populations. The pharmacodynamics (PD) of piperacillin-tazobactam is also discussed. What the reader will gain: The importance of appropriate antibiotic dosing in the context of the global tendency for reduced susceptibility of bacteria, including P. aeruginosa is emphasized. The interrelationship between PK and PD is discussed to provide an understanding of methods for procuring dosing regimens that increase the likelihood of clinical success for individual patients. Alternative dosing regimens, which may include administration by extended or continuous infusion of piperacillin-tazobactam as a mechanism to increase the likelihood of pharmacodynamic target attainment, are described. Take home message: Where piperacillin-tazobactam is required for treatment, applying knowledge of PK and PD characteristics can facilitate optimal outcomes.

The role of surveillance cultures in the prediction of susceptibility patterns of Gram-negative bacilli in the intensive care unit

Surveillance cultures may detect colonisation with drug-resistant Gram-negative bacteria and can be hypothesised to guide appropriate initial antibiotic treatment for intensive care unit (ICU) patients. We investigated the microbiological data of 228 episodes of nosocomial bloodstream infection (BSI) due to Gram-negative bacteria in an ICU in which piperacillin/tazobactam or meropenem was used empirically for serious infections, to evaluate the contribution of surveillance cultures to an appropriate choice of initial antibiotic therapy. Surveillance cultures were taken in advance of BSI in 218 (95.6%) of 228 episodes. Concordant organisms with identical identification and susceptibilities were found in prior surveillance cultures and subsequent blood cultures in 65 (29.8%) of 218 episodes. Surveillance cultures predicted resistance in 52.9% and 51.4% of BSIs caused by resistant pathogens to piperacillin/tazobactam and meropenem, respectively. The negative predictive value of surveillance cultures negative for a resistant organism also exceeded 90% for piperacillin/tazobactam and meropenem. Given that the overall resistant rates of BSI pathogens of our study were 11.3% to piperacillin/tazobactam and 16.4% to meropenem, surveillance cultures in our setting may provide important information on the probability of drug resistance of the causative pathogens and some utility in aiding empiric antibiotic therapy for ICU patients who subsequently develop BSI.

Doripenem population pharmacokinetics and dosing requirements for critically ill patients receiving continuous venovenous haemodiafiltration

OBJECTIVES Doripenem is a newer carbapenem with little data available to guide effective dosing during renal replacement therapy in critically ill patients. The objective of this study was to determine the population pharmacokinetics of doripenem in critically ill patients undergoing continuous venovenous haemodiafiltration (CVVHDF) for acute kidney injury (AKI). METHODS This was an observational pharmacokinetic study in 12 infected critically ill adult patients with AKI undergoing CVVHDF and receiving 500 mg of doripenem intravenously every 8 h as a 60 min infusion. Serial blood samples were taken on 2 days of treatment and used for population pharmacokinetic analysis with S-ADAPT. RESULTS The median (IQR) age was 62 (53-71) years, the median (IQR) weight was 77 (67-96) kg and the median (IQR) APACHE II score was 29 (19-32). The median blood, dialysate and replacement fluid rates were 200, 1000 and 1000 mL/h, respectively. A two-compartment linear model with doripenem clearance described by CVVHDF, renal or non-renal mechanisms was most appropriate. The mean value for total doripenem clearance was 4.46 L/h and volume of distribution was 38.0 L. Doripenem clearance by CVVHDF was significantly correlated with the replacement fluid flow rate and accounted for ∼30%-37% of total clearance. A dose of 500 mg intravenously every 8 h achieved favourable pharmacokinetic/pharmacodynamics for all patients up to an MIC of 4 mg/L. CONCLUSIONS This is the first paper describing the pharmacokinetics/pharmacodynamics of doripenem in critically ill patients with AKI receiving CVVHDF. A dose of 500 mg intravenously every 8 h was appropriate for our CVVHDF settings for infections caused by susceptible bacteria.

Influenza-associated bacterial pathogens in patients with 2009 influenza A (H1N1) infection: impact of community-associated methicillin-resistant Staphylococcus aureus in Queensland, Australia.

Background:  Secondary bacterial pneumonia due to community onset methicillin‐resistant Staphylococcus aureus (MRSA) has become a highly publicised cause of influenza‐associated death. There is a risk that case reports of fatal outcomes with post‐influenza MRSA pneumonia may unduly influence antibiotic prescribing.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version.

The Epidemiology of Pan/Extreme Drug Resistance

Multidrug resistance in Gram-negative bacilli is clearly of global concern. The purpose of this chapter is to review the epidemiology of organisms referred to as pan-resistant (PDR) or exhibiting extreme drug resistance (also referred to as extensive drug resistance—XDR). In order to better understand the epidemiology, it is first essential to define what is regarded as PDR or XDR.