Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring.

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration−time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

Congenital Chagas disease in a non-endemic area: Results from a control programme in Bergamo province, Northern Italy.

INTRODUCTION: In non-endemic countries, one of the most important routes of transmission of Trypanosoma cruzi is vertical transmission. The objective of this work is to report the results of the screening activities for the control of congenital Chagas Disease (CD) implemented in Bergamo province between January 2014 and December 2016. METHODS: The programme addressed Bolivian pregnant women settled in Bergamo province. All the eight hospitals offering antenatal and delivery care in that area were involved. We retrospectively calculated the coverage rate of the screening programme, the prevalence of CD in this population, as well as transmission rate to their offspring. RESULTS: During the study period, 376 Bolivian women accounted for 387 deliveries. The coverage rate of serologic screening was 85.6%. Confirmed seropositive women were 28, accounting for a prevalence of CD of 8.7% (95% IC 5.9-11.5). Among 29 children born to positive mothers, one infected child was detected (transmission rate of 4.3%, 95% IC 0-12.6) and treated accordingly. Other 13 children previously born from the same mothers were retrieved and tested for CD: no additional congenital cases were diagnosed. DISCUSSION: Our screening programme presented a high coverage, although widely variable in the different birthing facilities. National guidelines recommending CD testing in pregnant women would help to increase case detection countrywide.

Post-neurosurgical meningitis: Management of cerebrospinal fluid drainage catheters influences the evolution of infection.

BACKGROUND: In order to better define the pathogenic role of cerebrospinal fluid (CSF) drainage catheters in postoperative patients, we comparatively analyze the clinical course of device and non-device-related meningitis. METHODS: This is an observational, partially prospective, study on consecutive adult patients who developed meningitis after undergoing neurosurgical procedures at the Neurosurgery and Neurointensive care Departments, Spedali Civili, Brescia, Italy, between January 1999 and August 2007. RESULTS: All 77 consecutive post-neurosurgical meningitis events in 65 patients were included in the analysis. Most were classified as external ventricular drainage (EVD)-related meningitis (23 cases, group A), external spinal drainage (ESD)-related meningitis (12 cases, group B), and non-device-related post-neurosurgical meningitis (30 cases, group C). Proven meningitis was identified in 78.3%, 91.7% and 56.7% of the events, respectively. ESD-related meningitis had a shorter onset time vs EVD and non-device-associated meningitis (3 days versus 6 and 7 days, respectively). Median antibiotic treatment duration was 20, 17, and 22.5 days in groups A, B, and C, respectively. Overall, 8 patients (34.8%) in group A, 3 (25.0%) in group B, and 3 (10.0%) in group C died. Median time to become afebrile was shorter in group C than in group A (10 days versus 12 days, P = 0.04). Removal of the device later than 48 hours after meningitis onset, as well as implantation of a second device were associated with a slower time of meningitis resolution. CONCLUSIONS: Early device removal and avoiding implantation of a second device were associated with short illness duration. Larger studies are warranted to confirm the conclusions of this study.

Ultrasensitive assessment of residual low-level HIV viremia in HAART-treated patients and risk of virological failure.

BACKGROUND: Low-level viremia (LLV) is measurable, with enhanced assays, in many subjects with HIV RNA levels <50 copies per milliliter. The clinical consequences of LLV are unknown. METHODS: In a prospective study in HIV-1-infected adults, HIV RNA levels were determined with an ultrasensitive test (3 copies/mL) based on a real time polymerase chain reaction. The primary end point was to evaluate LLV prediction of virological failure, defined as a confirmed plasma HIV RNA level >50 copies per milliliter. RESULTS: One thousand two hundred fourteen patients were followed for (mean) 378 days. At baseline, 71.5% were <3 copies per milliliter below the limit of detection (BLD). The risk of failing highly active antiretroviral therapy in the following 4 months for patients BLD was 0.4% compared with a 3.2% risk for those with LLV (P < 0.0001; odds ratio: 7.52). There was a significant (P < 0.0001) linear relationship between the HIV RNA and the risk of virologic failure. LLV receiver operating curve analysis showed an area under the curve of 0.76 (95% confidence interval: 0.68 to 0.84) that significantly (P < 0.0001) predicted the risk of failure. The risk of an unconfirmed viral blip was higher in patients with LLV (3.9%) than in those BLD (1.1%) (P < 0.0001; odds ratio: 3.56). Longer exposure to antiretrovirals, current use of nonnucleoside reverse transcriptase inhibitors, longer time BLD, and current HIV RNA <3 copies per milliliter were independent predictors of a positive outcome. INTERPRETATION: Viral replication may be the cause of LLV, at least in some patients. A LLV >3 copies per milliliter is linked to a significant increment of risk of virological failure leading to drug resistance. Patients with measurable LLV should be managed to better evaluate, over time, the risk of failure and to limit its consequences.

Bactericidal activity of oxacillin and glycopeptides against Staphylococcus aureus in patients with endocarditis: looking for a relationship between tolerance and outcome.

BACKGROUND: There is no clear relationship between in vitro bactericidal activity tests and clinical outcome. We studied bactericidal activity of oxacillin, vancomycin and teicoplanin against Staphylococcus aureus isolates in patients with endocarditis and then we sought to determine if there was a relationship between in vitro bactericidal activity and clinical outcome. METHODS: Minimal bacteriostatic and minimal bactericidal concentrations were determined for Staphylococcus aureus strains isolated from patients with endocarditis following standardized methods. Medical records were reviewed retrospectively to collect data on antimicrobial susceptibility at admission, antimicrobial therapy, need for surgery, embolic events and outcome. RESULTS AND DISCUSSION: Sixty-two Staphylococcus aureus strains were studied in 62 patients with endocarditis. Overall, 91.9% definite, 21% methicillin resistant and 72.6% cured. Surgery was performed in 32.3% and embolic events were documented in 64.5%. Tolerance to oxacillin and teicoplanin was more common than vancomycin tolerance among methicillin susceptible Staphylococcus aureus. Among methicillin resistant Staphylococcus aureus teicoplanin was shown to have a higher rate of tolerance than vancomycin. No statistically significant differences on clinical outcome between oxacillin tolerant and oxacillin non tolerant Staphylococcus aureus infections were observed. Tolerance to oxacillin did not adversely affect clinical outcomes of patients with methicillin susceptible Staphylococcus aureus endocarditis treated with a combination of antimicrobials including oxacillin. The cure rate was significantly lower among patients with methicillin resistant Staphylococcus aureus endocarditis. CONCLUSIONS: In vitro bactericidal test results were not valid predictors of clinical outcome. Physicians need to use additional parameters when treating patients with staphylococcal endocarditis.

Linezolid and clindamycin improve the outcome of severe, necrotizing pneumonia due to community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).

The last decade has been characterized by the emergence of CA-MRSA strains associated with the production of Panton-Valentine leukocidin. We report a case of necrotizing pneumonia and septic shock caused by CA-MRSA, in which early recognition of the syndrome and appropriate treatment with two toxin-suppressing antibiotics improved the patient's outcome.

An unusual case of meningitis.

We report on a patient who presented at our hospital with fever, headache, neck pain, partial nuchal rigidity and decreased vision of the left eye. The clinical history, biochemical and instrumental exams performed suggested meningitis but the final hypothesis achieved was an unusual case of Neuro-Behcet-Disease (NBD) without orogenital ulcerations at presentation and with normal MRI findings, whose course was complicated by fatal cerebral venous sinus thrombosis and intracranial haemorrhage. The post-mortem results confirmed the diagnosis. This is a rare case confirmed by anatomo-pathological findings where NBD can present itself as an acute meningeal syndrome that mimics central nervous system infections, making diagnosis difficult and delaying treatment.

Hand hygiene and glove use behavior in an Italian hospital.

In an Italian hospital, we observed that hand hygiene was performed in 638 (19.6%) of 3,253 opportunities, whereas gloves were worn in 538 (44.2%) 1,218 of opportunities. We observed an inverse correlation between the intensity of care and the rate of hand hygiene compliance (R2=0.057; P<.001), but no such association was observed for the rate of glove use compliance (R2=0.014; P=.078). Rates of compliance with hand hygiene and glove use recommendations follow different behavioral patterns.

Mycobacterium szulgai identification by hsp65 gene sequencing in an HIV-positive patient with non-Hodgkin's lymphoma.

Mycobacterium szulgai, described for the first time in 1972, is a rare human pathogen that mainly causes pulmonary non-tubercular mycobacteriosis. We report its isolation and identification from a bronchoalveolar lavage specimen by hsp65 gene sequencing analysis in an HIV-positive patient with non-Hodgkin's lymphoma.

An outbreak of Serratia marcescens bloodstream infections associated with misuse of drug vials in a surgical ward.

We report an outbreak of Serratia marcescens bloodstream infection due to contamination of total parenteral nutrition solution by insulin or poligeline solution when single-use vials were used for multiple doses in a surgical ward. Four patients had severe sepsis, and no patient died. Multidose vials, used either correctly or incorrectly, may be associated with bloodstream infection.