Stable HIV-1 reservoirs on dolutegravir maintenance monotherapy: the MONODO study.

OBJECTIVES: Dolutegravir (DTG) is a highly effective integrase inhibitor with a strong genetic resistance barrier and a potential role in simplified HIV maintenance treatment. We assessed the feasibility of DTG maintenance monotherapy and measured HIV reservoirs on DTG monotherapy. METHODS: An interventional, open-label, single-arm study including eight virologically suppressed HIV-1-infected patients switched to DTG 50 mg once daily for 24 weeks was performed. HIV-1 RNA levels in plasma and cerebrospinal and seminal fluids were measured at baseline and week 24, as well as HIV-1 DNA in peripheral cells and DTG concentrations in these compartments. RESULTS: HIV-1 RNA remained undetectable in all samples of blood, cerebrospinal fluid and sperm throughout the 24 weeks, except for one cerebrospinal fluid sample with a value of 28 HIV-1 RNA copies/mL at week 24. One patient discontinued the study because of a neurological side effect. There was no change in the mean HIV-1 DNA level between baseline and week 24. Plasma and cerebrospinal fluid DTG concentrations reached therapeutic levels in all patients in these two compartments. CONCLUSIONS: In this small sample of carefully selected patients, HIV-1 reservoirs were well controlled on DTG monotherapy over a period of 24 weeks. Viral suppression was also maintained throughout follow-up.

Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study.

BACKGROUND: There is lack of recent multicenter epidemiological data on invasive aspergillosis (IA) among solid organ transplant recipient (SOTr) in the mold-acting antifungal era. We describe the epidemiology and outcomes of IA in a contemporary cohort of SOTr using the Swiss Transplant Cohort Study. METHODS: All consecutive SOTr with proven or probable IA between 01.05.2008 and 31.12.2014 were included. A case-control study to identify IA predictors was performed: 1-case was matched with 3-controls based on SOT type, transplant center, and time post-SOT. RESULTS: Among 2868 SOTr, 70 (2.4%) patients were diagnosed with proven (N: 30/70, 42.9%) or probable (N: 40/70, 57.1%) IA. The incidence of IA was 8.3%, 7.1%, 2.6%, 1.3%, and 1.2% in lung, heart, combined, kidney, and liver transplant recipients, respectively, Galactomannan immunoassay was positive in 1/3 of patients tested. Only 33/63 (52.4%) of patients presented with typical pulmonary radiographic findings. Predictors of IA included: renal insufficiency, re-operation, and bacterial and viral infections. 12-week mortality was higher in liver (85.7%, 6/7) compared to other (15.9%, 10/63; P < .001) SOTr. CONCLUSIONS: Invasive aspergillosis remains a rare complication post-SOT, with atypical radiographic presentations and low positivity rates of biomarkers posing significant diagnostic challenges. Although overall mortality has decreased in SOTr, it remains high in liver SOTr.

Relevance of fluoroquinolone use in a French teaching hospital.

OBJECTIVE: The objective of our study was to assess the good use of fluoroquinolone (FQ) in a French teaching hospital by a two round relevance review before and after proposal for better use of FQ prescriptions. PATIENTS AND METHODS: The relevance of FQ prescription according to regional guidelines was assessed using a standard card filled out retrospectively by physicians in the 3 previous months, in volunteer hospital wards. Then, two experts checked the relevance of prescriptions according to the regional antibiotherapy guidelines, a book called "Antibioguide", and determined a therapeutic index of adequacy for each card. The first survey (R1) took place in January 2008. The second survey (R2) took place in June 2009 to evaluate the impact of corrective measures, adopted at a meeting of the regional antibiotics commission in January 2009. RESULTS: Physicians in 18 wards completed 475 cards in R1 and physicians in 16 wards completed 263 in R2. The inappropriateness of FQ indication was significantly improved by 57% (P<0.001) between the two rounds and the rate of adequate cards was 33% in R1 and 55% in R2, giving an improvement of 66% (P<0.001). CONCLUSIONS: The improvement of FQ prescriptions and observance of guidelines demonstrate the importance of assessing the state of things before introducing corrective actions. "Antibioguide" was updated at the end of this study.

Antibiolor, the Lorraine antibiology network: update on 7 years of activity.

OBJECTIVE: The objective of the study was to assess the activity of the Antibiolor network, created in 2003, to promote antibiotic stewardship in Lorraine, and comply with the French Ministry guidelines issued in May 2002. METHODS: The authors described the objectives and structure of the network, actions implemented with physicians, pharmacists, community or hospital biologists, and evaluation. RESULTS: The network is made up of five committees supervised by a pilot committee. Over the previous 7 years, various actions were undertaken such as the drafting of guidelines for the hospitals and general practitioners, the creation of a hotline for advice on antibiotic treatment, the creation of a website, and giving information on infectious diseases via a quarterly letter sent to healthcare professionals. The network participated in continuous medical education for practitioners and organized the evaluation of professional practice in Lorraine hospitals. It also helped set up a network of community private laboratories for the study of resistance in the most frequently isolated bacteria, and implemented the monitoring of antibiotic consumption in hospitals. CONCLUSION: After 7 years, the Lorraine antibiology network has proved its beneficial role in terms of communication and scientific information for antibiotic stewardship. The Antibiolor network would like to follow other indicators in the future, such as the evolution of community antibiotic consumption in partnership with the public healthcare insurance.

[Impact of corrective measures on fluoroquinolones prescriptions for urinary tract infections during a 2-round relevance study]. / Amélioration de la prescription des fluoroquinolones dans les infections urinaires. Revue de pertinence à deux tours.

OBJECTIVES: Evaluating the impact of corrective measures on fluoroquinolones (FQ) prescriptions for urinary tract infections (UTI) during a 2-round relevance study on a regional scale. METHODS: FQ prescriptions of voluntary hospitals were checked by an infectious diseases physician and a pharmacist according to regional guidelines. A first round (R1) took place in January 2008, with feedback and proposal for personalized corrective measures in January 2009. A second round (R2) was organized in June 2009. UTI data were extracted and the results of the two rounds were compared. RESULTS: Four hundred and thirty-five and 302 FQ prescriptions for UTI, coming from 28 and 24 different hospitals, were analyzed at R1 and R2, respectively. Thirty-six percent and 55% of these prescriptions were entirely in accordance with regional guidelines, at respectively R1 and R2 (P<0.001). All the analyzed criteria (choice of the molecule, dosage, duration of the treatment) significantly improved between R1 and R2. The route of administration non-significantly deteriorated. The rate of FQ prescriptions for non conform indications decreased from 24% to 12% between R1 and R2 (P<0.05). CONCLUSION: Most hospitals of Lorraine took part in this study, confirming its feasibility on a regional scale. The regional guidelines were reviewed at the end of R2, taking into account the last national guidelines. There was a significant improvement of FQ prescriptions for UTI through better adhesion to the regional guidelines between the two rounds. This is probably due to first turn results feedback, and corrective measures suggestion.

15 years of antibiotic stewardship policy in the Nancy Teaching Hospital.

OBJECTIVES: The authors report the results of a 15-year antibiotic stewardship policy in the Nancy Teaching Hospital and assess the impact of reinforcing this policy on antibiotic consumption. METHODS: Antibiotic stewardship policy was initiated in the mid 90s and then reinforced from 2006 onwards. It was completed by prescription guidelines, nominative prescription of antibiotics, and an operational infectious diseases team (OIDT). The objectives were to promote antibiotic stewardship and decrease the use of extended broad spectrum or costly molecules and intravenous administration. Antibiotics consumption, as defined daily dose per 1000 patient days (DDD/1000PD) and in euros, was monitored from 2005 onwards. RESULTS: Between 2005 and 2008, overall yearly cost of antibiotics dropped by 34% (-€1,308,902) and consumption in DDD/1000PD by 10%. This drop in consumption concerned all antibiotic classes. Teicoplanin prescription dropped by more than 50% and use of fluoroquinolone IV decreased by 15% in 3years. The operational team's interventions were effective since nearly 80% of suggested prescription amendments were accepted by prescribers. CONCLUSIONS: This experiment shows that it is possible to implement antibiotic stewardship policy. Our results prove a significant decrease in overall consumption of antibiotic, a change in prescribing patterns, with a shift towards the use of cheaper antibiotics.

[Relevance of fluoroquinolone use in Nancy's hospital. Results of the first turn]. / Revue de pertinence de la prescription des fluoroquinolones au CHU de Nancy : résultats du premier tour.

OBJECTIVES: The objective was to evaluate the good use of fluoroquinolones in a hospital with a relevance review in the context of an approach to evaluation of professional practices at the regional level initiated by the Antibiolor network. METHOD: In February 2008, in each volunteer service, practitioners filled out a standardized form indicating indication, the name of the fluoroquinolone, route of administration and duration of treatment, retrospectively from 20 medical records on the last 3 months. Each one was analyzed by a binomial (doctors and pharmacists) according to the local Antibioguide. The degree of compliance requirements has been appreciated by a global index of adequacy of therapeutic consisting of six criteria. RESULTS: Eighteen units of Nancy's hospital filled 475 cards. The most frequent indications were pulmonary infections (38 %; 181/475) and urinary (23 %; 111/475). The fluoroquinolone indication was non-conform for 28 % of the cards (133/475). When the fluoroquinolone indication was justified, the association with another antibiotic was considered non-compliant in 20 % of cases (70/342), the choice of the molecule in 18 % (62/342), duration of treatment in 17 % (57/342), the dose in 13 % (45/342) and route of administration in 9 % (30/342). The requirements were entirely conform in 34 % of cases (160/475). CONCLUSION: The results were communicated to each participating service with corrective actions and then this experience has been repeated in May 2009.

[Relevance of fluoroquinolone use in Lorraine: results of the first survey]. / Revue de pertinence des fluoroquinolones en Lorraine: résultats de la première évaluation.

OBJECTIVES: The Antibiolor network assessed the good use of fluoroquinolones (FQ) in the French Lorraine region by a relevance review. METHODS: At the beginning of 2008, the experts in voluntary hospitals filled out a standard card mentioning the indication, FQ name, route, and duration according to prescriptions in the last 3 months. Two experts checked the relevance of prescriptions according to the local Antibioguide, and determined a score of therapeutic adequacy index for each card. Each establishment was given its results. Corrective measures were adopted at a meeting of the regional antibiotics commission in January 2009. RESULTS: One hundred and twenty-four units (61 medical, 33 surgical, 17 ICU, 2 ER, 11 long-stay hospital) in 28 hospitals filled 1538 cards. The most frequent indications were: pulmonary (632), urinary (445), digestive (130). The FQ indication was non-conform for 36% of the cards (n=554). When the FQ indication was justified (984 cards), the chosen molecule was non-conform in 222 cases (23%), dose in 115 cases (12%), duration in 250 cases (25%), and route of administration in 83 cases (8%). The prescriptions were entirely conform for 425 cards (28%). CONCLUSION: The Lorraine hospitals massively took part in this study. The second survey will use the same methodology. The objective will be to reduce the number of unjustified FQ prescriptions and to increase the number of conform cards.

[Staphylococcus aureus bacteremia and endocarditis]. / Bactériémies et endocardites àStaphylococcus aureus.

The prevalence of Stapylococcus bacteriaemia is increasing worldwide, because of the increasing use of invasive procedures leading to nosocomial infections, but also of a changing way of life (increasing fashion for tattoos or piercing, use of intravenous drugs). Infective endocarditis develops in 10-30% of the cases of staphylococcus bacteriaemia. Staphylococcus aureus endocarditis must be suspected when it develops in the year following heart surgery or implantation of permanent devices. In drug users, it usually involves the tricuspid valve. According to the resistance of the germ to meticillin, antibiotic therapy uses a combination of intravenous penicillin or glycopeptide and an aminoside. Other antibiotics such as fosfomycin, rifampicin, fusidic acid, or clindamycin can be used when aminosides are contra-indicated. The role of newer antibiotic agents, such as daptomycin or linezolide, remains to be established.

[Non-valvular cardiac devices endocarditis]. / L'endocardite sur matériel de stimulation intracardiaque.

The risk of infective endocarditis on pacemaker or ICD is not negligible and has increased in recent years. Several host-related, procedure-related, or device-related risk factors have been recognized. Owing to its potential severity, the possibility of infective endocarditis should be envisaged in patients with repeated pulmonary infections or documented bacteremia and transesophageal echocardiography should then be used. The most common germs causing pacemaker endocarditis are staphylococci. Treatment requires prolonged antibiotic therapy and retrieval of the pacemaker and leads.

Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database.

Infective endocarditis due to coagulase-negative staphylococci is increasingly recognized as a difficult-to-treat disease associated with poor outcome. The aim of this report is to describe the characteristics and outcome of patients with prosthetic valve endocarditis (PVE) due to coagulase-negative staphylococci versus those of patients with PVE due to Staphylococcus aureus and viridans streptococci. Patients were identified through the International Collaboration on Endocarditis Merged Database. A total of 54 cases of coagulase-negative staphylococci PVE, 58 cases of S. aureus PVE, and 63 cases of viridans-streptococci-related PVE were available for analysis. There was no difference between the three groups with respect to the type of valve involved or the rate of embolization. However, heart failure was encountered more frequently with coagulase-negative staphylococci (54%) than with either S. aureus (33%; p=0.03) or viridans streptococci (32%; p=0.02). In addition, valvular abscesses complicated 39% of infections due to coagulase-negative staphylococci compared with 22% of those due to S. aureus (p=0.06) and 6% of those due to viridans streptococci (p<0.001). Mortality was highest in patients with S. aureus and coagulase-negative staphylococcal endocarditis (47 and 36%, respectively; p=0.22) and was considerably lower in patients with viridans streptococcal endocarditis (p=0.002 compared to patients with coagulase-negative staphylococcal endocarditis). The results of this analysis demonstrate the aggressive nature of coagulase-negative staphylococcal PVE and the substantially greater morbidity and mortality associated with this infection compared to PVE caused by other pathogens.

Enterococcal prosthetic valve infective endocarditis: report of 45 episodes from the International Collaboration on Endocarditis-merged database.

Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20% vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics, mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers in this study.

[New French recommendations for the prophylaxis of infectious endocarditis]. / Nouvelles recommandations françaises de prophylaxie de l'endocardite infectieuse.

New French recommendations on infective endocarditis (IE) prevention were recently published and mark a turning point in the history of antibiotic prophylaxis. Endocarditis is an evolving disease, and its clinical and microbiological profile dramatically changes over time. The French surveys that were conducted in 1991 and 1999 showed variations in underlying heart disease with a decrease in native valvular disease and an increase of IE in patients without previously known heart disease. Moreover, the distribution of responsible microorganisms dramatically changed over time, with a marked decrease of oral streptococci. In addition, some dogmas are now challenged. First of all, the part of responsibility of dental procedures is debated, as dental bacteraemia possibly responsible of endocarditis are more likely due to daily manoeuvres such as tooth brushing or chewing gum than to occasional dental procedures. Moreover, as suggested by case-control studies, efficacy--or lack of efficacy--of antibiotic prophylaxis is far from being clinically proved. For all these reasons, the proportion of theoretically avoidable endocarditis seems very low, and the benefit of largely and systematically applied antibiotic prophylaxis may be discussed, not only in terms of financial cost but also in terms of microbiological threat of emergence of antibiotic resistant bacteria. So, the general idea of those new recommendations was to maintain the principle and the modalities of antibiotic prophylaxis, but to limit its indications to situations at high benefit to risk ratio, i.e. procedures at high risk in patients at high risk. Depending on the situation, antibiotic prophylaxis may be either recommended or become optional and decision-making factors are defined. Furthermore, the importance of general prophylaxis was emphasised, concerning more specifically oral and cutaneous hygiene, and patients and practitioners' education, such as, for example, recommendations on blood cultures to be performed before any antibiotic treatment in case on fever occurring in a patient at risk during the 3 months following a procedure at risk.

A standardized procedure for quantitation of CD11b on polymorphonuclear neutrophil by flow cytometry: potential application in infectious diseases.

An up-regulation of the surface marker CD11b has been demonstrated during polymorphonuclear (PMN) cell activation. CD11b over-expression is often associated with inflammation and is considered as an early marker of infection. However, the absence of standardized assay and the variability of preanalytical settings leading to PMN artifactual activation have compromised the interest of this marker. In the present study a standardized quantitative flow cytometry assay directly performed in whole blood has been used to determine CD11b expression on PMN cells. The results indicate that quantitative flow cytometry can provide consistent CD11b density values between laboratories provided that a calibration system is used including specific calibrators, reagents and protocols. This method allowed us to evidence an up-regulation of CD11b expression for infected patients. This quantitation is a standardized and potentially useful method in clinical situations implying quantitative CD11b expression variations.

[Infectious endocarditis in France today]. / Aspects actuels de l'endocardite infectieuse en France.

Infectious endocarditis (IE) is an uncommon condition carrying a relatively high mortality and morbidity. Two epidemiological studies, undertaken eight years apart, provide data allowing an appreciation of changes in the epidemiological and clinical profiles of IE. They show a progressive increase in the age of patients affected by IE and a decrease in percentage of IE on native pathological valves and valvular prostheses, compensated by the increase in incidence of IE occurring in patients with no known underlying cardiac disease. Moreover, there has been a change in microbiological profile, with the emergence of Streptococcus bovis and increase in staphylococcal IE, a decrease in IE due to oral streptococci and an improvement in microbiological diagnosis with negative blood cultures. Finally, from the therapeutic point of view, surgery is used more frequently and at an earlier stage of the disease. The global mortality of IE at the end of the initial hospital period remains 16%.

Comparison of combination therapy regimens for treatment of human immunodeficiency virus-infected patients with disseminated bacteremia due to Mycobacterium avium. ANRS Trial 033 Curavium Group. Agence Nationale de Recherche sur le Sida.

We conducted a randomized, open-label trial in 42 French hospitals to compare the clinical and bacteriologic efficacy of combination therapy with clarithromycin/clofazimine (Clm/Clof) with that of combination therapy with clarithromycin/rifabutin/ethambutol (Clm/Rib/Eth) as treatment for Mycobacterium avium bacteremia. One hundred forty-four human immunodeficiency virus-seropositive patients older than 18 years of age who had CD4 lymphocyte counts of <100/mm3 and a blood culture positive for M. avium were enrolled in the study. The main measures of outcome were blood cultures, abatement of clinical symptoms (fever), and survival. Treatment success (defined as patient living, either no fever or a reduction of > or = 1 degrees C in initial body temperature, and a blood culture negative for M. avium) was similar in both treatment groups at months 2 and 6. However, following initial resolution of infection, relapse of M. avium bacteremia occurred in more patients in the Clm/Clof group than in the Clm/Rib/Eth group (22 vs. six, respectively; P < .001); these relapses were accompanied by emergence of strains resistant to clarithromycin in 21 and two patients, respectively. In conclusion, combination therapy with Clm/Rib/Eth prevented relapse of mycobacterial disease and, compared with combination therapy with Clm/Clof, was associated with a significant decrease in the emergence of resistant M. avium strains in HIV-infected patients treated for at least 28 weeks.