Simplified equations using two concentrations to calculate area under the curve for antimicrobials with concentration-dependent pharmacodynamics: daptomycin as a motivating example.

The effects of several antimicrobial agents are predicted by the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC). Peak (Cp) and trough (Ct) concentrations are often measured clinically as surrogates of AUC because actual computation of AUC from 1 or 2 samples requires sophisticated mathematical methods. Given that the effects of daptomycin are predicted by AUC/MIC, our objective was to compare simple equation calculated AUC based on Cp and Ct to model integrated AUC.

A cluster of fulminant Clostridium difficile colitis in an intensive care unit in Italy.

We describe, for the first time, a cluster of lethal fulminant health-care associated Clostridium difficile (CD) colitis in Italy, observed in the intensive care unit (ICU) of an Italian tertiary care hospital in Rome. For all cases the cause of ICU admission was CD-related septic shock. Three out of seven patients were residents in a long-term care facility in Rome, and the others had been transferred to the ICU from different medical wards of the same hospital.

Rapidly fatal hemorrhagic pneumonia and group A Streptococcus serotype M1.

We report 3 cases of fulminant hemorrhagic pneumonia in previously health patients. Sudden-onset hemoptysis and dyspnea developed; all 3 patients and died <12 h later of massive pulmonary bleeding, despite aggressive supportive care. Postmortem analysis showed that the illnesses were caused by group A Streptococcus emm1/sequence type 28 strains.

ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients.

Healthcare-associated infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These evidence-based guidelines have been produced after a systematic review of published studies on infection prevention and control interventions aimed at reducing the transmission of MDR-GNB. The recommendations are stratified by type of infection prevention and control intervention and species of MDR-GNB and are presented in the form of 'basic' practices, recommended for all acute care facilities, and 'additional special approaches' to be considered when there is still clinical and/or epidemiological and/or molecular evidence of ongoing transmission, despite the application of the basic measures.

Early, intermediate and late infectious complications after transcatheter or surgical aortic-valve replacement: a prospective cohort study.

Transcatheter aortic valve implantation (TAVI) has been proposed to treat older surgical high-risk patients with severe symptomatic aortic stenosis. There are no data regarding short-term and long-term infectious complications in these patients. The objective of this study was to define the incidence, aetiology and outcome of early and late infectious complications following TAVI compared with patients >65 years old undergoing traditional surgical aortic replacement (SAR).

SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients.

Purpose: We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs).

Methods: Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals.

Results: Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs.

Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial.

Importance: β-Blocker therapy may control heart rate and attenuate the deleterious effects of β-adrenergic receptor stimulation in septic shock. However, β-Blockers are not traditionally used for this condition and may worsen cardiovascular decompensation related through negative inotropic and hypotensive effects.

Objective: To investigate the effect of the short-acting β-blocker esmolol in patients with severe septic shock.

Considerations for higher doses of daptomycin in critically ill patients with methicillin-resistant Staphylococcus aureus bacteremia.

Background: Higher daptomycin doses are advocated for select methicillin-resistant Staphylococcus aureus (MRSA)-related infections, but the probabilities of target attainment (PTA) and toxicity of these doses have not been characterized in critically ill patients.

Methods: We evaluated the plasma pharmacokinetics (PK) and clinical outcomes of a cohort of critically ill patients treated with daptomycin 6-8 mg/kg/day for primarily Staphylococcus species-related infections. Daptomycin concentrations were measured intensively over the initial 96-hour dosing period.

Risk factors for acute kidney injury in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics: a retrospective cohort study.

Introduction: Use of colistin methanesulfonate (CMS) was abandoned in the 1970s because of excessive nephrotoxicity, but it has been reintroduced as a last-resort treatment for extensively drug-resistant infections caused by gram-negative bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumonia). We conducted a retrospective cohort study to evaluate risk factors for new-onset acute kidney injury (AKI) in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics.

Methods: The cohort consisted of 279 adults admitted to two general ICUs in teaching hospitals between 1 April 2009 and 30 June 2011 with 1) no evidence on admission of acute or chronic kidney disease; and 2) treatment for more than seven days with CMS and/or other nephrotoxic antimicrobials (NAs, that is, aminoglycosides, glycopeptides).

Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study.

Objective: β-blocker therapy may control heart rate and attenuate the deleterious effects of β-stimulating catecholamines in septic shock. However, their negative chronotropy and inotropy may potentially lead to an inappropriately low cardiac output, with a subsequent compromise of microvascular blood flow. The purpose of the present pilot study was to investigate the effects of reducing heart rate to less than 95 beats per minute in patients with septic shock using the β-1 adrenoceptor blocker, esmolol, with specific focus on systemic hemodynamics and the microcirculation.

Increased risk of cognitive impairment in cirrhotic patients with bacterial infections.

Background & Aims: A causal relationship between infection, systemic inflammation, and hepatic encephalopathy (HE) has been suggested in cirrhosis. No study, however, has specifically examined, in cirrhotic patients with infection, the complete pattern of clinical and subclinical cognitive alterations and its reversibility after resolution. Our investigation was aimed at describing the characteristics of cognitive impairment in hospitalized cirrhotic patients, in comparison with patients without liver disease, with and without infection.

Daptomycin plus trimethoprim/sulfamethoxazole combination therapy in post-neurosurgical meningitis caused by linezolid-resistant Staphylococcus epidermidis.

Post-neurosurgical infection is a serious complication that occurs in approx. 4% of all patients undergoing neurosurgical procedures and is associated with high morbidity and mortality rates and prolonged length of intensive care unit (ICU) stay. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are the most frequent pathogens involved in CNS post-neurosurgical meningitis.

Candidemia in Neurosurgical Intensive Care Unit: preliminary analysis of the effect of topical Nystatin prophylaxis and adequate source control on patients with early tracheostomy intubation.

Introduction: The present study represents a preliminary evaluation of the impact of topical nystatin prophylaxis administration and adequate CVC management on reducing the chance of developing candidemia in neurosurgical intensive care unit (NICU) patients.

Materials And Methods: We conducted a case-control study at the nine bed NICU of the Policlinico "Umberto I" teaching hospital in Rome, Italy, during the period from January 2011 to July 2012. We compared eight patients with culture proven Candida bloodstream infection (CBSI) with a control group of 19 patients who did not have evidence of CBSI.

Variability of pharmacokinetic parameters in patients receiving different dosages of daptomycin: is therapeutic drug monitoring necessary?

Pharmacokinetic studies of daptomycin in septic patients indicate that pharmacokinetic parameters may be altered. The purpose of this clinical investigation is to determine the pharmacokinetics of daptomycin in a population of hospitalized patients with clinically significant gram-positive infections and receiving daptomycin. Daptomycin was measured using an isocratic HPLC technique.

Worrisome trend of new multiple mechanisms of linezolid resistance in staphylococcal clones diffused in Italy.

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).

Daptomycin serum levels in critical patients undergoing continuous renal replacement.

Background: Daptomycin pharmacokinetics has not been extensively studied in patients undergoing continuous renal replacement therapy (CRRT).

Methods: The aim of the study was to collect pharmacokinetics and clinical data of patients undergoing CRRT and receiving daptomycin therapy. Daptomycin was measured using an isocratic high-performance liquid chromatography technique.

High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality.

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is becoming a common cause of healthcare-associated infection in Italy, with high morbidity and mortality. Prevalent CR-KP clones and resistance mechanisms vary between regions and over time. Therapeutic approaches and their impact on mortality have to be investigated.

Patient risk factors for outer membrane permeability and KPC-producing carbapenem-resistant Klebsiella pneumoniae isolation: results of a double case-control study.

Background: In the 1,200-bed university hospital "Umberto I" in Rome, Italy, we observed a dramatic substitution of a precedingly well-documented Klebsiella pneumoniae clone (ST37) with ertapenem resistance by outer membrane permeability modification (Porin-ER-Kp) with a new K. pneumoniae strain expressing carbapenem resistance due to K. pneumoniae carbapenemase production (KPC-CR-Kp).