Paediatric antibiotic prescriptions in primary care in the Alpes-Maritimes area of southeastern France between 2008 and 2013.

France has remained among the top five European countries for ambulatory antibiotic consumption since such monitoring began in 1998. Young children are major antibiotic consumers, in spite of the viral origin of most infections in this population. Recommendations were updated in 2011 to limit prescriptions. In order to assess their impact, diagnoses and prescriptions were compared in a population of children attending daycare centres in southeastern France in 2008 and 2012. Trends in the reimbursement of paediatric antibiotic prescriptions by the national health insurance (NHI) for the whole area were also studied. Distribution of diagnoses accounting for antibiotic treatment and type of antibiotic prescribed over the previous 3 months to children below 4 years of age attending daycare centres in the Alpes-Maritimes area in southeastern France were compared between 2008 and 2012 prior to and following the availability of these new recommendations. Trends in reimbursed ambulatory antibiotic prescriptions by general practitioners and paediatricians in the area were studied for this age group from 2008 to 2012 and in 2013. The majority of recorded diagnoses concerned upper respiratory tract infections (URTI). Inappropriate antibiotic prescription persisted for colds and bronchitis in similar proportions during both surveys. Improvement in the choice of antibiotic with fewer prescriptions for third-generation cephalosporins was observed both in daycare centres and according to NHI data; however, this was mainly recorded among paediatricians. The management of paediatric URTI still needs improvement, pointing to the need to investigate and adequately address the reasons for inappropriate antibiotic prescription.

A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication.

Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.

Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.

OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.

[Pulmonary rehabilitation after lung resection for tumor - a feasibility study]. / Intérêt de la réhabilitation respiratoire après résection pulmonaire pour tumeur.

INTRODUCTION: To investigate the safety, feasibility and effectiveness of an inpatient pulmonary rehabilitation program (i-PR) after lung resection (LR) for cancer. METHODS: Between January 2007 and December 2009, we conducted a prospective observational study on patients admitted in our institution. An i-PR was offered to all patients. They completed respiratory function tests and a quality of life (QoL) questionnaire at the start and after completing the i-PR. RESULTS: During the study, 154 out of 175 patients who underwent LR and who were admitted in our center followed an i-PR. The remaining 21 patients were excluded because of emergency re-hospitalisation (10 patients), anticipated departure (six patients) or refusal to participate (five patients). Most functional parameters in the 154 treated patients improved between the beginning and the end of their stay: FVC (69.9% versus 79.6%; P<0.0001); FEV(1) (61.2% versus 69.9%; P<0.0001); timed walk-6MWT (356 m versus 444 m; P<0.0001) and constant work cycle ergometry test (281 s versus 683 s; P<0.0001). Also, the EORTC QLQ-C30 and the EORTC QLQ-LC13 improved during the stay, especially global health status (50.5 versus 64.5; P<0.0001). CONCLUSION: Postoperative PR is safe and could positively impact on functional status and QoL among this population.

A decade-long surveillance of nasopharyngeal colonisation with Streptococcus pneumoniae among children attending day-care centres in south-eastern France: 1999-2008.

The antimicrobial resistance and serotype distribution of Streptococcus pneumoniae (SP) among children attending day-care centres in south-eastern France were monitored from 1999 to 2008, before and after interventions promoting prudent antibiotic use initiated in 2000 and the availability of pneumococcal conjugate vaccine in 2003. Antibiotic susceptibility and serotypes of SP isolates were determined on nasopharyngeal samples of children aged 3-40 months attending day-care centres, from January to March 1999, 2002, 2004, 2006 and 2008. SP carriage fell from 54% to 45%, and SP with diminished susceptibility to penicillin (PDSP) fell from 34% to 19%. Antibiotic prescriptions dropped from 63% to 38% of children, but third-generation cephalosporins were increasingly prescribed. The overall antibiotic susceptibility increased. Over 90% of the children had received at least one vaccine dose in 2008. Vaccine serotypes 6B, 9V, 19F and 23F (76%) in 1999 were replaced by non-vaccine types (95%) in 2008, among which were 15 (20%), 19A (15%), 23A/B (10%) and 6A (9%). Serotypes 6A, 19A and 15 accounted for over 50% of PDSP strains in 2008 versus 6% in 1999. Children now mostly harbour non-vaccine types; however, PDSP isolates are mainly recruited among these. Vaccine-related benefits may be threatened by combined vaccine- and antibiotic-driven selective pressure.

Evaluating counseling outcome on adherence to prophylaxis and follow-up after sexual HIV-risk exposure: a randomized controlled trial.

OBJECTIVE: Post-exposure prophylaxis (PEP) is recommended for the management of sexual HIV-risk exposure. However, a high percentage of exposed patients discontinue both their 28-day prophylaxis course before 15 days and HIV testing follow-up before M3. The objective of this study is to assess the efficacy of a counseling intervention in enhancing both adherence to PEP and HIV testing follow-up. METHODS: Between 1 June 2004 and 31 December 2005, 54 patients exposed to sexual HIV-risk exposure were included in a multicenter, prospective, controlled, randomized trial, comparing a group receiving a counseling intervention in addition to traditional medical management (intervention group (IG), n=28) vs. a control group (CG, n=26). Patients in the IG received interactive counseling interventions focused on adherence to PEP and to HIV testing follow-up, led by specially trained nurses. The main outcome measures were proportion of patients achieving 100% adherence to PEP as evaluated on D15 by a self-completed patient questionnaire and on HIV testing on D45 and M3. RESULTS: Groups were well balanced at baseline for age, sex, and circumstances of exposure. The proportion of 100% adherent patients to PEP was significantly higher in the IG compared to the CG (54% vs. 23%, p=0.036). Patients in the IG were more likely to complete the HIV testing follow-up at D45 (86% vs. 54%, p=0.023) and M3 (68% vs. 38%, p=0.056). CONCLUSIONS: This study suggests the effectiveness of a counseling program to enhance adherence to both PEP and HIV testing follow-up after sexual exposure.

Enhanced T-cell apoptosis in human septic shock is associated with alteration of the costimulatory pathway.

T-cell apoptosis during septic shock (SS) has been associated with deleterious outcome, but the mechanisms of apoptosis are not well understood. As T-cells are not infected in bacterial infection, our hypothesis was that deleterious interactions between lymphocytes and monocytes could be involved. This is a cross-sectional study of 27 patients presenting with community-acquired SS, 23 infected patients without SS and 18 controls. Cytofluorometric techniques were used to study apoptosis, the costimulatory pathway and cytokine synthesis. Apoptosis was increased in SS compared to infected patients without SS and controls: the median values were 18, 2 and 3%, respectively, for CD4(+) T-cells (P < 0.001), and 12, 5 and 2%, respectively, for CD8(+) T-cells (P < 0.001). Patients with SS exhibited significant CD152 over-expression on T-cells, while CD86 expression was decreased on monocytes (P = 0.004). The synthesis of interleukin-2 was decreased in patients with SS compared to the other groups, while secretions of interferon-gamma and TNF-alpha were not altered. Ten surviving patients with SS showed a trend towards the normalisation of these parameters on day 7. In SS, T-cell apoptosis is related, at least in part, to the alteration of the costimulatory pathway, which, in turn, leads to significant modification of the cytokine network.

[Influenza vaccination coverage rate in children with underlying chronic disorders in 7 French pediatric wards]. / Couverture vaccinale vis-à-vis de la grippe chez les enfants de la région parisienne atteints d'une affection de longue durée.

UNLABELLED: In France, annual influenza vaccination is recommended and free of charge for children with chronic disease (chronic lung, heart or kidney disease, diabetes, haemoglobinopathy, immune deficiency). The national goal is to reach 75% influenza vaccination coverage by 2008, but data on coverage in high risk children are limited. OBJECTIVES: To estimate the influenza vaccination coverage in children with an underlying chronic health condition in the Paris region, during in- or out-patient visit at hospital. METHODS: A multicentre cross-sectional descriptive study was carried out over 2 months before the 2004-2005 flu vaccination campaign in 7 French paediatric hospitals (Paris region). Inclusion criteria for this survey were: children aged 6 months to 18 years, with an underlying chronic disease requiring annual influenza vaccination, with a vaccination card available, so as to check their vaccination status. Reasons for non vaccination were recorded. RESULTS: Data from 239 children were analysed. 56% of patients were males (mean age: 8.1 years). Two patients had 2 separate underlying chronic disorders; 69% had a haemoglobinopathy, 16.3% had a chronic respiratory disease, and 7.5% had diabetes. The influenza vaccination rate for 2003-2004 was 43.7% (haemoglobinopathy: 55.5%; chronic respiratory diseases: 12.8%). This rate increased from 20.4% to 43.7% between 1999 and 2003. Less than 16% of parents remembered having received a voucher for free vaccination from the National Health Insurance Agency. CONCLUSION: Efforts are still needed to achieve the 2008 objectives of 75% coverage.

In vitro selection of mutants of Streptococcus pneumoniae resistant to macrolides and linezolid: relationship with susceptibility to penicillin G or macrolides.

OBJECTIVES: To evaluate the rate of acquisition of resistance to linezolid and macrolides in Streptococcus pneumoniae isolates with different levels of susceptibility to penicillin and erythromycin. MATERIALS AND METHODS: Thirty strains of S. pneumoniae were tested by serial passages in subinhibitory concentrations of each antibiotic by the spiral method. The four copies of the 23S rRNA rrl gene of parent strains and linezolid-resistant mutants were amplified and sequenced. RESULTS: The rate of acquisition of macrolide resistance did not differ when C-14 and C-16 macrolides were tested. Resistance to linezolid in strains susceptible to penicillin and erythromycin was difficult to produce. For mutants with low-level resistance to linezolid the cut-off value of the MIC was between 6 and 8 mg/L depending on the strain. All linezolid-resistant mutants displayed a mutation in 2-4 copies of the 23S rRNA rrl gene, mainly the G2576U mutation (27/30) with an additional C2610U mutation observed in certain mutants. Two new mutations were also noted, namely C2612A and C2571G. In three linezolid-resistant mutants no mutation was identified within the studied domain, suggesting another mechanism of resistance. CONCLUSIONS: Linezolid resistance in pneumococcal strains susceptible to penicillin and macrolides was more difficult to obtain than with macrolides. Increased resistance to these agents may therefore influence the clinical use of linezolid.

In the era of highly active antiretroviral therapy, why are HIV-infected patients still admitted to hospital for an inaugural opportunistic infection?

OBJECTIVES: To identify factors related to delayed testing, and delayed or interrupted care-seeking or treatment uptake, among HIV-infected patients. DESIGN: HIV-infected patients hospitalized for an opportunistic infection (OI) cases were included in a prospective study and compared with controls matched by age and sex who had regular follow-up and treatment. Patients were asked to complete a questionnaire about their therapeutic itinerary and their socioeconomic, psychological and medical characteristics. RESULTS: Seventy patients were matched with 140 controls. According to their therapeutic itinerary prior to admission, cases were subdivided into four groups among which three will be more particularly studied: nontested patients (NT) (24%; n=17), known HIV-infected patients with no medical follow-up (NF) (30%; n=21); and noncompliant patients (NC) (36%, n=25). Characteristics of NT and NF patients included a predominantly sexual mode of contamination (P=0.01), continuing occupational activity (P=0.01) despite a low mean Karnofsky index (P=0.001) and unfavourable virological and immunological parameters. NT patients displayed a low degree of anxiety, and lacked awareness concerning risk of contamination and HIV-related symptoms. HIV-status announcement (P=0.04) and the benefits of medical follow-up (P=0.05) were less favourably perceived by NF patients than by controls, and were associated with a high degree of anxiety in NF patients. NC patients had a weaker commitment to follow-up and treatment, and more frequent treatment discontinuation associated with a higher rate of interruption of follow-up in a context of social difficulties. CONCLUSIONS: Patients ignorant of their HIV status, patients NF and NC have very specific characteristics. More appropriate approaches are needed regarding screening and access to care in order to reduce the incidence of delayed care-seeking.

[Type of child care and nasopharyngeal S. pneumoniae and H. influenzae carriage in children in the Alpes-Maritimes]. / Mode de garde et portage naso-pharyngé de S. pneumoniae et H. influenzae d'enfants dans les Alpes-Maritimes.

OBJECTIVE: To compare the prevalence rates of nasopharyngeal carriage of Streptococcus pneumoniae (SP) and of SP with diminished susceptibility to penicillin (PDSP) according to two types of day care, i.e. children in group day-care (GDC) and those attended by a child minder (CM) before and after the implementation of a local public health campaign promoting prudent antibiotic use in pediatric care. METHODS: Two cross sectional studies were conducted in each care setting in 1999, 2000 and 2002, on a random sample of children. RESULTS: Initial prevalence rates for SP before the campaign were 54% in the GDC group in 1999 and 34% in the CM group in 2000, with 63% and 52% PDSP, respectively. In 2002 theses rates were 58 and 33% for SP (p<10(-5)) and 64 and 53% for PDSP, respectively. The proportion of children who received antibiotics decreased in both care settings between the two surveys, from 47 to 37% in the CM group (p=0.03) and from 60 to 51% in the GDC group (p=0.03). CONCLUSION: These results are in favor of the child minder setting and also illustrate the positive impact of a public health campaign on the frequency of antibiotic prescriptions.

[Diagnosis of a metastatic valvular tumor in a living patient]. / Tumeur métastatique valvulaire diagnostiquée du vivant du malade.

INTRODUCTION: The discovery of an endocardial mass always raises the question of its nature. Infectious endocarditis is the most frequent cause, but others diagnoses must be considered. EXEGESIS: We report a case of endocardial metastasis originating from an upper respiratory tract epidermoid carcinoma in a 48-years-old man. The diagnosis was established while the patient was alive, and survival at the time of writing is 8 months. This case report provides an opportunity for discussion of the differential diagnosis when confronted with an endocardial tumor, i.e. bacterial endocarditis, non-bacterial thrombotic endocarditis, primary cardiac tumors, metastatic osteogenic sarcoma and Libman-Sachs endocarditis. CONCLUSION: Non bacterial thrombotic endocarditis and valvular metastasis should be considered upon discovery of a valvular tumor, in the context of neoplastic disease. The prognosis of endocardial metastasis is poor, but early diagnosis and appropriate management should eventually prolong survival.

Relevance and complications of intravenous infusion at the emergency unit at Nice university hospital.

OBJECTIVE: Insertion of peripheral venous catheters (PVCs) is current practice within the hospital environment and particularly in the emergency department (ED). This simple yet invasive technique may result in venous thrombosis, infection or mechanical complications. We conducted a prospective study at the Nice University Hospital ED in order to determine the frequency, relevance and complications of peripheral venous cannulation. PATIENTS AND METHODS: Fourteen 24 h periods were surveyed over the months of May and June 2000, during which 2515 patients over 16 years of age attended the unit. Demographic and medical data were recorded for every patient who received a PVC. These patients were followed at 12 h intervals until the catheter was removed. Reasons for PVC, time left in place, and eventual complications were recorded. Justification for PVC was evaluated upon arrival at the ED, upon exiting the ED and in some cases within the hospital ward. RESULTS: Six hundred and thirty of 2515 patients (25%) received a PVC (290 women (46%) and 340 men (54%); meanage 58 years). Indication for the PVC was considered unjustified in 24.8% of cases upon arrival at the ED, and 33.8% upon leaving the ED. Upon admission in a hospital ward after passing through the ED, out of 318 patients, the PVC was left in place for no reason in 63 (20%). Overall, 390 PVCs were followed until the time of their removal. Mean duration of IV infusion was 28 h. Among these 390 patients, 62 (15.9%) developed complications, of which 54 (13.6%) had thrombophlebitis and 9 (2.3%) developed local infection. Mean duration of PVC left in place for patients with complications was 50 h vs 25 h for patients with no complications (P<0.001). CONCLUSION: Insertion of a PVC is common practice especially in EDs. The excessive use of this procedure leads to extra cost and iatrogenic complications. A renewed definition of its indication and raised awareness among hospital staff concerning the risks involved with this standard procedure should result in less use of PVC and fewer complications.

Intracellular concentration of protease inhibitors in HIV-1-infected patients: correlation with MDR-1 gene expression and low dose of ritonavir.

BACKGROUND: Protease inhibitors (PIs) are substrates for the P-glycoprotein (P-gp/170) encoded by the multi-drug resistance gene (MDR-1). HIV infection is associated with increased expression of P-gp. The role of MDR gene overexpression in clinical pharmacokinetics is not known. METHOD: We determined by HPLC, at trough and peak levels, the current PI concentrations in plasma (P) and in peripheral blood mononuclear cells (PBMCs) (intracellular concentration [IC]) from 49 HIV-infected patients receiving different treatment combinations: nelfinavir ([NFV] n = 12); indinavir ([IDV] n = 10); amprenavir ([APV] n = 5); ritonavir (RTV) 100 bid/IDV 800 mg bid (n = 6); RTV 400 bid/IDV 400 mg bid (n = 3); RTV 100 bid/saquinavir (SQV) 600 mg tid (n = 9); APV 600 bid/RTV 100 mg bid (n = 4). We determined the mean ratio of intracellular/plasma PI concentration for each treatment group. The MDR-1 gene expression was determined by a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). HIV viral load was simultaneously measured. RESULTS: 49 patients (mean age 41 +/- 8.7 years; mean CD4 cell count 418 [57-972]; mean HIV RNA 2.1 +/- 0.8 log(10)) were included in the study. Patients who overexpressed the MDR-1 gene had significantly lower trough intracellular PI levels (p =.02) or lower intracellular accumulation of PI (p =.042). Patients treated with low-dose RTV in combined regimens with detectable RTV intracellular concentration showed lack of MDR-1 gene expression (p =.01). Patients with HIV RNA < 40 copies/mL had significantly higher RTV intracellular accumulation (p =.029). CONCLUSION: In HIV-infected patients, IC of PI is inversely correlated with MDR-1 gene overexpression. Undetectable viral load was associated with the use of low-dose RTV, probably linked to better intracellular accumulation of the drug. Nevertheless, further investigation is needed to confirm these results.

Consensual treatment of plasmodium falciparum malaria does not lead to adequate quinine blood concentrations.

Since 1996, we have a common protocol in the Infectious Diseases Department and the Intensive Care Unit for the administration of quinine in case of Plasmodium falciparum malaria. Patients were classified as uncomplicated form of malaria (UFM) or severe form of malaria (SFM) according to WHO criteria, adding parasitemia >5% as a criteria of SFM. Treatment of SFM should consist of a 4 h infusion of 16 mg/kg quinine-base loading dose, followed by 8 mg/kg every 8 h. Patients with UFM receive quinine-base, 8 mg/kg every 8 h. A therapeutic index of 10-15 mg/l was considered adequate. Hypoglycemia and cardiotoxicity were the two main adverse effects of quinine to be investigated. In order to verify that these modalities for quinine administration are associated with adequate quinine blood concentrations, we have reviewed the pharmacological data and the occurrence of adverse effects. Between April 1996 and December 2000, 95 patients were hospitalised: 25 with SFM and 70 with UFM: 78/95 patients (82%) received adequate treatment and 26/95 (28%) of the patients presented an overdosage of quinine. Six severe adverse effects were observed, even in case of adequate quinine administration. Consensual treatment of malaria does not confer adequate quinine blood concentrations, and toxic effects are still common.

Changing trends in pregnancy outcome among HIV-infected women between 1985 and 1997 in two southern French university hospitals.

OBJECTIVES: To analyze risk factors for pregnancy outcome among HIV-infected women before and after introduction of AZT prophylaxis in 1994. STUDY DESIGN: A prospective, two-center observational study conducted from 1 January 1985 to 31 December 1997. PATIENTS: Pregnant HIV-infected women followed in one of the obstetrics units during the study period. MAIN OUTCOME MEASURES: pregnancy outcome (normal delivery, ectopic pregnancy, spontaneous abortion, voluntary termination of pregnancy (TOP) according to year of pregnancy, age at pregnancy professional status, marital status, ethnic origin, mode of contamination, stage of disease, partner's human immunodeficiency virus (HIV) status and prior pregnancy. RESULTS: One thousand one hundred and three pregnancies among 937 HIV-infected women were studied. Mean age of patients was 28.1 +/- 4.9 years. Pregnancy outcomes were distributed as follows: 473 normal deliveries, 589 TOP, 9 ectopic pregnancies and 32 spontaneous abortions. The proportion of TOP decreased from 59.4% before 1994 to 37.5% from 1994 (P < 0.001). In univariate analysis, mode of transmission, marital status, ethnic origin, partner's HIV status and prior pregnancy were also significantly correlated with pregnancy outcome. However, after adjustment by logistic regression for each period (before and after 1994), mode of transmission no longer appeared to influence pregnancy outcome. CONCLUSION: Effective prevention of mother-to-child transmission of HIV infection appears to have influenced HIV-infected women's decisions on continuing their pregnancy to term. Incidence of voluntary TOP has decreased significantly after introduction of AZT.

Ventricular patch endocarditis caused by Propionibacterium acnes: advantages of gallium scanning.

Propionibacterium acnes is a weakly pathogenic commensal of the skin. When isolated from blood cultures it is often considered a contaminant. However, P. acnes may be responsible for severe infections and its role in certain cases of infectious endocarditis has now been definitely established.(1) We report a case of endocarditis due to P. acnes stemming from a ventricular patch and revealed by a gallium 67 scan.

Gradient plate method to induce Streptococcus pyogenes resistance.

In recent years, increasing numbers of Streptococcus pyogenes (GAS) strains displaying resistance to macrolides have been reported in Finland, Japan, Asia and Spain. Antibiotic use has been shown to be a risk factor for infection with and carriage of drug-resistant streptococci. The aim of this study was to compare in-vitro development of resistance of streptococci to beta-lactams (penicillin, amoxycillin, cefotiam and cefuroxime) and erythromycin by serial passages in subinhibitory concentrations of antibiotics (subMICs) by gradient plate method. Three clinical strains of GAS were tested. Two were susceptible to erythromycin (MIC = 0.015 mg/L and 0.013 mg/L) and one resistant. Serial passages were performed daily by gradient plate method until a four-fold increase of the MIC was achieved. GAS variants obtained after serial passages in beta-lactams had MICs increased at least four-fold. They remained susceptible to these antibiotics. With erythromycin, final MICs reached intermediate and resistant level. Results obtained in this study with erythromycin are in good correlation with clinical studies showing that prior exposure to macrolides may help to facilitate the emergence of drug-resistant strains of streptococci.

Epidemiology of bacterial infection during management of open leg fractures.

In a randomised double-blind trial conducted between 1990 and 1994, 616 patients from 43 centres, pefloxacin (group P, 316 patients) and a cefazolin-oxacillin combination (group C, 300 patients) were compared in the prophylaxis of bone infection after grade 1 and 2 open leg fractures. Samples were obtained at emergency, before and during surgery, and from drain aspirates. Antimicrobial susceptibility, slime production and adherence properties of the bacteria were tested. Cultures at emergency and before surgery showed similar distributions of gram-positive and gram-negative bacteria in both groups, while wound closure and infecting isolates showed prevailing gram-positive bacteria in group P and gram-negative bacteria in group C. Positive cultures at each stage were correlated with the occurrence of infection but were not predictive of the infecting species, which were nosocomial bacteria in most cases. Positive cultures at wound closure warn of a higher infection risk. Twenty-one of 316 (6.6%) patients in group P and 24 of 300 (8%) in group C were considered infected within 3 months. The difference is not significant (chi-square test = 0.42; P = 0.51). Infecting strains were isolated from 38 patients (group P, 18; group C, 20). Infecting species, although not predictable, appear to be those escaping the spectrum of the prescribed antimicrobial prophylaxis.