Impact of therapeutic drug monitoring of antibiotics in the management of infective endocarditis.

Treatment of infective endocarditis (IE) is based on high doses of antibiotics with a prolonged duration. Therapeutic drug monitoring (TDM) allows antibiotic prescription optimization and leads to a personalized medicine, but no study evaluates its interest in the management of IE. We conducted a retrospective, bicentric, descriptive study, from January 2007 to December 2019. We included patients cared for IE, defined according to Duke's criteria, for whom a TDM was requested. Clinical and microbiological data were collected after patients' charts review. We considered a trough or steady-state concentration target of 20 to 50 mg/L. We included 322 IE episodes, corresponding to 306 patients, with 78.6% (253/326) were considered definite according to Duke's criteria. Native valves were involved in 60.5% (185/306) with aortic valve in 46.6% (150/322) and mitral in 36.3% (117/322). Echocardiography was positive in 76.7% (247/322) of cases. After TDM, a dosage modification was performed in 51.5% (166/322) (decrease in 84.3% (140/166)). After initial dosage, 46.3% (82/177) and 92.8% (52/56) were considered overdosed, when amoxicillin and cloxacillin were used, respectively. The length of hospital stay was higher for patient overdosed (25 days versus 20 days (p = 0.04)), and altered creatinine clearance was associated with overdosage (p = 0.01). Our study suggests that the use of current guidelines probably leads to unnecessarily high concentrations in most patients. TDM benefits predominate in patients with altered renal function, but probably limit adverse effects related to overdosing in most patients.

Suction drainage fluid culture during septic orthopaedic surgery, a retrospective study.

We evaluated the usefulness of suction drainage fluid culture after septic orthopaedic surgery to predict early surgical reintervention. We conducted a retrospective observational study, at the Groupe Hospitalier Paris Saint-Joseph between 2014 and 2019. All the patients undergoing septic orthopaedic surgery, with perioperative samples and a postoperative suction drainage device, were enrolled. We compared the group with positive or negative postoperative drainage fluid cultures, respectively, on surgical outcome. We included 246 patients. The drainage fluid culture was positive in 42.3% of the cases. Early surgical reintervention concerned 14.6% of the cases (n = 36), including 61.1% of patients with positive drainage fluid culture (n = 22/36). The risk factors associated with positive drainage fluid cultures were the debridement of the infected site (without orthopaedic device removal), an infection located at the spine, perioperative positive cultures to Staphylococcus aureus. The complete change of the orthopaedic device, and coagulase-negative staphylococci on the preoperative samples, was associated with negative drainage fluid cultures. Positive drainage fluid culture was predictive of early surgical reintervention, and coagulase-negative staphylococci in the preoperative samples and knee infection were predictive of surgical success. Postoperative drainage fluid cultures were predictive of early surgical reintervention. Randomized multicentric studies should be further conducted.

Population pharmacokinetics and dosing simulations of amoxicillin in obese adults receiving co-amoxiclav.

BACKGROUND: Pneumonia, skin and soft tissue infections are more frequent in obese patients and are most often treated by co-amoxiclav, using similar dosing regimens to those used for non-obese subjects. No data are available on amoxicillin pharmacokinetics among obese subjects receiving co-amoxiclav. MATERIALS AND METHODS: Prospective, single-centre, open-label, non-randomized, crossover pharmacokinetic trial having enrolled obese otherwise healthy adult subjects. A first dose of co-amoxiclav (amoxicillin/clavulanate 1000/200 mg) was infused IV over 30 min, followed by a second dose (1000/125 mg) administered orally, separated by a washout period of ≥24 h. We assayed concentrations of amoxicillin by a validated ultra HPLC-tandem MS technique. We estimated population pharmacokinetic parameters of amoxicillin by non-linear mixed-effect modelling using the SAEM algorithm developed by Monolix. RESULTS: Twenty-seven subjects were included in the IV study, with 24 included in the oral part of the study. Median body weight and BMI were 109.3 kg and 40.6 kg/m2, respectively. Amoxicillin pharmacokinetics were best described by a two-compartment model with first-order elimination. Mean values for clearance, central volume, intercompartmental clearance and peripheral volume were, respectively, 14.6 L/h, 9.0 L, 4.2 L/h and 6.4 L for amoxicillin. Oral bioavailability of amoxicillin was 79.7%. Amoxicillin Cmax after oral administration significantly reduced with weight (P = 0.013). Dosing simulations for amoxicillin predicted that most of the population will achieve the pharmacodynamic target of fT>MIC ≥40% with the regimen of co-amoxiclav 1000/200 mg (IV) or 1000/125 mg (oral) q8h for MICs titrated up to 0.5 mg/L (IV) and 1 mg/L (oral). CONCLUSIONS: Pharmacokinetic/pharmacodynamic goals for amoxicillin can be obtained in obese subjects.

Clinical evaluation of subcutaneous administration of cefepime.

OBJECTIVES: Cefepime is a fourth-generation cephalosporin active against Pseudomonas aeruginosa and most Enterobacteriaceae. Intravenous (IV) administration is the standard route of prescription. However, subcutaneous administration (SC) may represent an interesting alternative. We aimed to evaluate SC administration of cefepime versus the IV route in geriatric patients. PATIENTS AND METHODS: Multicenter retrospective analysis in patients treated with cefepime by SC route who underwent plasma concentration monitoring. RESULTS: Twelve patients were included in the SC group and matched to 12 patients in the IV group. The median and mean Cmin levels were 29.05mg/L [14.2-48.2]; 33.4mg/L (±21.8) in the SC group and 31.9mg/L [26.5-51.7]; 39.6mg/L (±27) (P=NS) in the IV group. No local SC administration-related complications were reported. No relapse was observed over six months of follow up. CONCLUSION: Subcutaneous use of cefepime seems to have the same clinical and microbiological effectiveness as parenteral administration.

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium.

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

Infective endocarditis: Clinical presentation, etiology, and early predictors of in-hospital case fatality.

OBJECTIVE: We aimed to assess the clinical presentation, microbial etiology and outcome of patients presenting with infective endocarditis (IE). PATIENTS AND METHODS: We conducted a four-year retrospective study including all patients presenting with IE. RESULTS: We included 121 patients in the study. The median age was 74.8years. Most patients had native valve IE (57%). Staphylococcus aureus accounted for 24.8% of all IE. Surgery was indicated for 70 patients (57.9%) but actually performed in only 55 (44.7%). Factors associated with surgery were younger age (P=0.002) and prosthetic valve IE (P=0.001). Risk factors associated with in-hospital mortality were diabetes mellitus (OR=3.17), chronic renal insufficiency (OR=6.62), and surgical indication (OR=3.49). Mortality of patients who underwent surgery was one sixth of that of patients with surgical indication who did not have the surgery (P<0.001).

Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference.

Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.

Nosocomial outbreak of staphylococcal scalded skin syndrome in neonates: epidemiological investigation and control.

Over a three-month period, 13 neonates developed staphylococcal scalded skin syndrome (SSSS) in a maternity unit, between four and 18 days after their birth. An epidemiological and descriptive study followed by a case-control study was performed. A case was defined as a neonate with blistering or peeling skin, and exfoliative toxin A Staphylococcus aureus positive cultures. Controls were selected at random from the asymptomatic, non-colonized neonates born on the same day as the cases. All staff members and all neonates born during the outbreak period were screened for carriage by nasal swabs and umbilical swabs, respectively. S. aureus isolates were polymerase chain reaction (PCR) screened for etA gene and genotyped by pulsed-field gel electrophoresis (PFGE). Two clusters of eight and five cases were identified. Receiving more than one early umbilical care procedure by the same ancillary nurse was the only risk factor identified in the case-control study (odds ratio=15, 95% confidence intervals 2-328). The ancillary nurse suffered from chronic dermatitis on her hands that favoured S. aureus carriage. Exfoliative-toxin-A-producing strains, as evidenced by PCR and indistinguishable by PFGE, were isolated from all but one of the SSSS cases, from four asymptomatic neonates, from two staff members and from the ancillary nurse's hands. Removal of the ancillary nurse from duty, infection control measures (isolation precautions, chlorhexidine handwashing and barrier protections), and treatment of the carriers (nasal mupirocin and chlorhexidine showers) led to control of the epidemic. In conclusion, this study emphasizes the need for tight surveillance of chronic dermatitis in healthcare workers.

A control programme for MRSA (methicillin-resistant Staphylococcus aureus) containment in a paediatric intensive care unit: evaluation and impact on infections caused by other micro-organisms.

Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly reported as a hospital-acquired pathogen in intensive care units (ICUs). The inconsistent application of hygiene measures by healthcare workers accounts largely for the epidemic dissemination of such resistant strains. The efficacy of a control programme to prevent spread of MRSA was assessed in our paediatric ICU (PICU) from April 1992 to December 1995. Patients initially had weekly MRSA cultures taken from samples of anterior nares and perineum, but from January 1994, cultures were also obtained upon admission. Immediately after notification, all MRSA carriers were isolated. Education of hospital staff was an essential component of our programme. Nosocomial infection rates were recorded retrospectively in 1992 and 1993, and prospectively in 1994 and 1995. Incidence rates between 'pre-programme' and 'programme' periods were compared. The rate of MRSA infection decreased from 5.9-0.8/1000 Patient-Days (PD), (P < 10(-7). MRSA carriage also decreased from 34-2% (P < 10(-9) and the ratio of MRSA to all S. aureus fell from 71-11% (P < 10(-4). The decrease in the global incidence of infection from 20.1-13.9/1000 PD (P = 0.002) was due only to the decrease in MRSA infection. However, between 1994 and 1995, there was a significant increase in the number of transplant patients despite a constant patient/nurse ratio. The nosocomial infection rates caused by other micro-organisms decreased among the transplant patients from 64.8-33.2/1000 transplanted PD (P = 0.009) between 1994 and 1995. At the same time, we observed a slight increase of infections in non-transplanted patients, which may have been due to the effect of increased overall workload on those patients who were supposed to have fewer nosocomial risk factors. We conclude that implementation of infection control measures directed towards limiting person-to-person spread was effective in controlling high MRSA infection rates in a PICU, but it is important to allow enough time for staff to carry out hygiene practices thoroughly.

[Acute pyelonephritis in women. Short-term hospitalization]. / Pyélonéphrite aiguë de la femme. Hospitalisation de courte durée.

One-hundred women suffering from acute pyelonephritis were hospitalized for less than 4 days on average, in order to make a diagnosis based on bacteriology and computerized tomography (CT) and to bring fever down with a 21-day antibiotic therapy. In cases of acute pyelonephritis due to a urinary tract obstacle, endoscopic uereteral drainage was added to the antibiotic treatment. In the absence of obstacle, medical treatment was sufficient to obtain apyrexia. Fluoroquinolone therapy made it possible to reduce the hospital stay to 2 or 3 days, depending on whether the lesions observed at CT were triangular or round.

Value of an immunofluorescence assay for the detection of Pneumocystis carinii in Bronchoalveolar lavage.

An indirect immunofluorescence monoclonal antibody assay was found to have higher sensitivity than usual stains for the detection of Pneumocystis carinii, particularly in bronchoalveolar lavage fluids in which there are only a few parasites, as in HIV-patients or in HIV+ patients with prophylaxis or treatment. For patients without any therapy, when different stains give conflicting results, decisions on therapeutic approaches to be used should consider the patient's clinical and biological status. Prospective studies are necessary to evaluate the predictive value of low parasitism in asymptomatic immunosuppressed patients.