Emergence of resistance after therapy with antibiotics used alone or combined in a marine model

A murine model of peritonitis allowing detection and quantification of in-vivo acquired resistance during short term therapy has been used in order to evaluate the capacity of antimicrobial combinations to limit emergence of resistance, as compared to individual components of the regimens. Mice were challenged intraperitoneally with 108 cfu of bacteria. Two hours later, a single antibiotic dose was injected subcutaneously: amikacin (15 mg/kg), ceftriaxone (50 mg/kg), pefloxacin (25 mg/kg), amikacin + ceftriaxone, amikacin + pefloxacin or ceftriaxone + pefloxacin. Escherichia coli and Staphylococcus aureus never became resistant. Single drug therapy yielded resistant mutants in Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae and Pseudomonas aeruginosa as follows: 74% of ceftriaxone-treated animals, 57% of pefloxacin treated animals and 27% of amikacin treated animals. All the tested combinations reduced the frequency of in-vivo acquired resistance produced by single drugs, and no combination selected resistance when the separate agents of the combination did not. Combining antimicrobial agents limits the risk of emergence of resistance during antibiotic therap

Awareness of vaccination status and its predictors among working people in Switzerland

BACKGROUND: Adult vaccination status may be difficult to obtain, often requiring providers to rely on individual patient recall. To determine vaccination status awareness and the sociodemographic predictors of awareness for tetanus, hepatitis A and B, tick born encephalitis (TBE) and influenza vaccination. METHODS: Multivariate analyses were used to evaluate a questionnaire survey of 10 321 employees (4070 women and 6251 men aged 15–72 years) of two companies in Switzerland. RESULTS: Among 10 321 respondents, 75.5% reported knowing their tetanus vaccination status, 64.1% hepatitis A, 61.1% hepatitis B, 64.3% TBE and 71.9% influenza. Between 1 in 4 and 1 in 3 employees were not aware of their vaccination status. Differences in awareness for the five vaccinations considered correlated with gender and language. These differences persisted in multivariate analyses. CONCLUSION: Women employees, German-speaking employees and employees who paid more attention to their diet were more often aware of their vaccination status. A more reliable and readily accessible data source for vaccination status is needed in order to capitalize on opportunities to update vaccinations among Swiss employees

e-Pilly TROP Maladies infectieuses tropicales

L’e-Pilly TROP est un ouvrage d’infectiologie tropicale destiné aux médecins et aux étudiants en médecine des pays francophones du Sud. La prise en compte des différents niveaux de la pyramide sanitaire dans ces pays le rend aussi accessible aux infirmiers des centres de santé communautaires urbains et des structures de santé intermédiaires des zones rurales. Par définition, les Pays En Développement accroissant progressivement leurs capacités de diagnostic biologique et de traitement, les outils de prise en charge correspondent aux moyens des niveaux périphériques comme à ceux des niveaux hospitaliers de référence

The Impact of Combination Antiretroviral Therapy and its Interruption on Anxiety, Stress, Depression and Quality of Life in Thai Patients

OBJECTIVE: Investigation on anxiety, stress, depression, and quality of life (QoL) within STACCATO, a randomised trial of two treatment strategies: CD4 guided scheduled treatment interruption (STI) compared to continuous treatment (CT). PARTICIPANTS: Thai patients with HIV-infection enrolled in the STACCATO trial. METHODS: Anxiety, depression assessed by the questionnaires Hospital Anxiety and Depression Scale (HADS) and DASS, stress assessed by the Depression Anxiety Stress Scale (DASS), and QoL evaluated by the HIV Medical Outcome Study (MOS-HIV) questionnaires. Answers to questionnaires were evaluated at 4 time-points: baseline, 24 weeks, 48 weeks and at the end of STACCATO. RESULTS: A total of 251 patients answered the HADS/DASS and 241 answered the MOS-HIV of the 379 Thai patients enrolled into STACCATO (66.2 and 63.6% respectively). At baseline 16.3% and 7.2% of patients reported anxiety and depression using HADS scale. Using the DASS scale, 35.1% reported mild to moderate and 9.6% reported severe anxiety; 8.8% reported mild to moderate and 2.0% reported severe depression; 42.6% reported mild to moderate and 4.8% reported severe stress. We showed a significant improvement of the MHS across time (p=0.001), but no difference between arms (p=0.17). The summarized physical health status score (PHS) did not change during the trial (p=0.15) nor between arm (p=0.45). There was no change of MHS or PHS in the STI arm, taking into account the number of STI cycle (p=0.30 and 0.57) but MHS significant increased across time-points (p=0.007). CONCLUSION: Antiretroviral therapy improved mental health and QOL, irrespective of the treatment strategy

HIV-1 Residual Viremia Correlates with Persistent T-Cell Activation in Poor Immunological Responders to Combination Antiretroviral Therapy

BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Salmonella enterica serovar Typhi de sensibilité diminuée à la ciprofloxacine

International audienceThe use of fluoroquinolone (FQ) as first line therapy for typhoid fever should be reconsidered because of the emergence of Salmonella Typhi and Paratyphi A strains with decreased susceptibility to FQ, mainly from Asia. Relapse can occur when ciprofloxacin MIC is over 0.12 mg/l, as illustrated by our case report. Azithromycin can be used successfully for patients infected with reduced ciprofloxacin susceptibility isolates. Literature review led us to suggest a new therapeutic strategy for uncomplicated typhoid fever, the antibiotic was chosen according to nalidixic acid susceptibility and ciprofloxacin MIC of the strain. High-dose intravenous ceftriaxone (4 g per day) is always efficient in first line therapy. Depending on FQ susceptibility testing results, it is relayed by oral therapy with a FQ (ciprofloxacin 500 mg bid for 7 days) if the isolate has maintained susceptibility, or azithromycin (1 g first day and 500 mg per day, 7 days) if the isolate is resistant to nalidixic acid or has a ciprofloxacin MIC superior to 0.12 mg/l.La place des fluoroquinolones (FQ) dans le traitement de première intention des fièvres typhoïdes (FT) doit être remise en question du fait de l’émergence de souches de Salmonella enterica serovar Typhi et Paratyphi A de sensibilité diminuée aux FQ en provenance d’Asie du sud-est. Des rechutes peuvent survenir quand la CMI de la ciprofloxacine est supérieure ou égale à 0,125 mg/l, comme l’illustre le cas clinique que nous rapportons. L’azithromycine a une efficacité démontrée sur les souches de sensibilité diminuée à la ciprofloxacine. À partir d’une revue de la littérature, nous proposons un nouveau schéma thérapeutique des FT non compliquées, où l’antibiothérapie est guidée par la sensibilité à l’acide nalidixique et la CMI de la ciprofloxacine de la souche. La ceftriaxone intraveineuse à forte dose (4 g/24 h) est toujours efficace en première intention ; elle est initiée dans l’attente des données de sensibilité de la souche. Un relais par voie orale est pris avec une FQ (ciprofloxacine 500 mg deux fois par jour, sept jours) en cas de sensibilité conservée, ou l’azithromycine (1 g le premier jour, puis 500 mg par jour, sept jours) en cas de résistance à l’acide nalidixique ou de CMI de la ciprofloxacine supérieure ou égale à 0,125 mg/l