Factors associated with emergence of pristinamycin-resistant Staphylococcus aureus in a dermatology department: a case-control study.

BACKGROUND: Pristinamycin is used for the treatment of Staphylococcus aureus skin infection. Staphylococcus aureus pristinamycin resistance is usually low. The frequency of pristinamycin-resistant S. aureus (PRSA) increased in the Caen University Hospital dermatology department from 1% in 1998 to >11% in 1999-2002. OBJECTIVES: This study aimed to identify the factors associated with PRSA acquisition. METHODS: Incidences of PRSA and pristinamycin consumption were calculated for the dermatology department and for the rest of the hospital from 1997 to 2007. Individual factors of PRSA acquisition in the dermatology department from 2000 to 2001 were analysed in a retrospective case-control study including 23 cases of PRSA skin colonization or infection and 46 controls with pristinamycin-susceptible S. aureus. Clonal relatedness of isolates was analysed by pulsed-field gel electrophoresis and pristinamycin resistance genes were detected by polymerase chain reaction. Conditional logistic regression was performed to analyse the relationship between pristinamycin resistance and epidemiological and microbiological data. RESULTS: PRSA frequency and pristinamycin consumption were significantly higher in the dermatology department than in other hospital departments. Two epidemic clones of two and six isolates were found for periods of 1 and 2 months, respectively. Thirteen of the 23 PRSA isolates (57%), including all isolates of the two epidemic clones, were found 48 h after the hospitalization or later. PRSA was associated with pristinamycin use during the previous year [odds ratio (OR) 5.60, 95% confidence interval (CI) 1.41-22.22], cumulative use of antibiotics exceeding 1 week during the previous year (OR 4.63, 95% CI 1.47-14.54) and methicillin resistance (OR 6.35, 95% CI 1.38-29.15). CONCLUSIONS: Results suggest that antimicrobial selective pressure and microbial cross-transmission are involved in PRSA acquisition.

[Use of a program-specific website to disseminate data on antimicrobial susceptibility of clinical isolates from the Tigecycline Evaluation and Surveillance Trial (TEST)]. / Le site internet TEST d'évaluation de l'activité de la tigécycline sur des isolats cliniques : un outil pratique pour obtenir des données de sensibilité actualisées.

Tigecycline Evaluation and Surveillance Trial (TEST) is an international surveillance study designed to assess the in vitro activity of tigecycline and 11 comparators against a range of important clinical pathogens from both the community and the hospital. The updated data obtained from the TEST program are integrated in a database server and available with a web application. The website has been designed to disseminate data collected from the international TEST program to the medical community and has been developed to be user-friendly. The use of this program-specific website can be made in a timely manner to extract antimicrobial resistance data of major microorganisms based on chosen selection criteria. This article describes how to use this web-based program for different analyse-types and the multiple options to display search results. Data can be presented in a table or as a graph or diagram, according to the source of the isolate, type of unit, resistance pattern of the pathogen. The website also allows the user to compare the data of antimicrobial testing at a national or regional level. It provides within a few minutes details on the activity of tigecycline and 11 comparators against clinical isolates collected all around the world. Main results of the TEST program on the in vitro activities of tigecyline against more 65,000 clinical isolates throughout the world are presented. The internet gives infectious diseases specialists and microbiologists the opportunity to have immediate access to continuously updated surveillance data. The TEST website should be helpful to clinicians to better select agents in severe infections, particularly for empirical treatment, that is at a time when the choice of the most appropriate antibiotic is essential for the outcome of the patient.

Activities of the combination of quinupristin-dalfopristin with rifampin in vitro and in experimental endocarditis due to Staphylococcus aureus strains with various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics.

We evaluated the activities of quinupristin-dalfopristin (Q-D), alone or in combination with rifampin, against three strains of Staphylococcus aureus susceptible to rifampin (MIC, 0.06 microg/ml) and to Q-D (MICs, 0.5 to 1 microg/ml) but displaying various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics: S. aureus HM1054 was susceptible to quinupristin and dalfopristin (MICs of 8 and 4 microg/ml, respectively); for S. aureus RP13, the MIC of dalfopristin was high (MICs of quinupristin and dalfopristin for strain RP13, 8 and 32 microg/ml, respectively); and S. aureus HM1054R was obtained after conjugative transfer of macrolide-lincosamide-streptogramin B constitutive resistance to HM1054, and the MIC of quinupristin for this strain was high (MICs of quinupristin and dalfopristin, 64 and 4 microg/ml, respectively). In vitro time-kill curve studies showed an additive effect [corrected] between Q-D and rifampin, at a concentration of four times the MIC, against the three strains. Rabbits with aortic endocarditis were treated 4 days with Q-D, rifampin, or their combination. In vivo, the combination was highly bactericidal and synergistic against strains susceptible to quinupristin (HM1054 and RP13) and sterilized 94% of the animals. In contrast, the combination was neither synergistic nor bactericidal against the quinupristin-resistant strain (HM1054R) and did not prevent the emergence of mutants resistant to rifampin. We conclude that the in vivo synergistic and bactericidal activity of the combination of Q-D and rifampin against S. aureus is predicted by the absence of resistance to quinupristin but not by in vitro combination studies.

Influence of resistance to streptogramin A type antibiotics on the activity of quinupristin-dalfopristin in vitro and in experimental endocarditis due to Staphylococcus aureus.

We evaluated the activity of quinupristin-dalfopristin (Q-D) against three clinical strains of Staphylococcus aureus susceptible to Q (MIC, 8 microg/ml) and Q-D (MICs, 0.5 to 1 microg/ml) but displaying various levels of susceptibility to D. D was active against S. aureus HM 1054 (MIC, 4 microg/ml) and had reduced activity against S. aureus RP 13 and S. aureus N 95 (MICs, 32 and 64 microg/ml, respectively). In vitro, Q-D at a concentration two times the MIC (2xMIC) produced reductions of 4.3, 3.9, and 5.8 log(10) CFU/ml after 24 h of incubation for HM 1054, RP 13, and N 95, respectively. Comparable killing was obtained at 8xMIC. Q-D-resistant mutants were selected in vitro at a frequency of 2 x 10(-8) to 2 x 10(-7) for the three strains on agar containing 2xMIC of Q-D; no resistant bacteria were detected at 4xMIC. Rabbits with aortic endocarditis were treated for 4 days with Q-D at 30 mg/kg of body weight intramuscularly (i.m.) three times a day (t.i.d.) or vancomycin at 50 mg/kg i.m. t.i.d. In vivo, Q-D and vancomycin were similarly active and bactericidal against the three tested strains compared to the results for control animals (P < 0.01). Among animals infected with RP 13 and treated with Q-D, one rabbit retained Q-D-resistant mutants that were resistant to Q and to high levels of D (MICs, 64, >256, and 8 microg/ml for Q, D, and Q-D, respectively). We conclude that the bactericidal activity of Q-D against strains with reduced susceptibility to D and susceptible to Q-D is retained and is comparable to that of vancomycin. Acquisition of resistance to both Q and D is necessary to select resistance to Q-D.

Influence of inducible cross-resistance to macrolides, lincosamides, and streptogramin B-type antibiotics in Enterococcus faecium on activity of quinupristin-dalfopristin in vitro and in rabbits with experimental endocarditis.

The influence of inducible cross-resistance to macrolides, lincosamides, and streptogramin B (MLS(B)) type antibiotics (inducible MLS(B) phenotype) on the activity of quinupristin-dalfopristin was investigated against Enterococcus faecium in vitro and in rabbits with experimental endocarditis. In vitro, quinupristin-dalfopristin displayed bacteriostatic and bactericidal activities against a MLS(B)-susceptible strain similar to those against two strains with the inducible MLS(B) phenotype. In addition, induction of the two MLS(B)-resistant strains with quinupristin (0.016 to 1 microg/ml) or quinupristin-dalfopristin (0.08 to 0.25 microg/ml) increased the MICs of quinupristin from 8 microg/ml to 32 to > 128 microg/ml, but did not modify the MIC of dalfopristin (2 microg/ml) or quinupristin-dalfopristin (0.5 microg/ml). In a rabbit endocarditis model, quinupristin-dalfopristin was as active as amoxicillin against the MLS(B)-susceptible E. faecium strain. In contrast, the activity of quinupristin-dalfopristin was significantly decreased in animals infected with either of the two inducible MLS(B)-resistant strains (P < 0.05), although no mutants resistant to quinupristin-dalfopristin were detected. Against the clinical strain with the inducible MLS(B) phenotype, quinupristin-dalfopristin was not effective and was less active than amoxicillin (P < 0.001); however, the activity of the combination of amoxicillin and dalfopristin-quinupristin was superior to that of amoxicillin (P < 0.01). The different impact of the inducible MLS(B) phenotype in E. faecium on the activity of quinupristin-dalfopristin in vitro and in experimental endocarditis may be related to the reduced diffusion of dalfopristin compared with that of quinupristin into cardiac vegetations that we previously reported. This result emphasizes the importance of the constant presence of dalfopristin at the site of infection to ensure synergism with quinupristin.

Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation.

Strenuous exercise may be associated with immune suppression. However, the underlying mechanism is not known. A decrease in the plasma level of glutamine, which is utilised at a high rate by cells of the immune system, and an increase in the plasma level of some cytokines may impair immune functions such as lymphocyte proliferation after prolonged, exhaustive exercise. In two separate studies of the Brussels marathon, using similar protocols, the time course of the changes in the plasma concentrations of some amino acids (glutamine, glutamate, alanine, tryptophan and branched chain amino acids), acute phase proteins and cytokines (interleukins IL-1 alpha, IL-2, IL-6, tumour necrosis factor type a) was measured in male athletes. The numbers of circulating leucocytes and lymphocytes were also measured. Amino acid and cytokine concentrations have not previously been measured concomitantly in marathon runners; the measurement of some of these parameters the morning after the marathon (16 h) is novel. Another novel feature is the provision of glutamine versus placebo to marathon runners participating in the second study. In both studies the plasma concentrations of glutamine, alanine and branched chain amino acids were decreased immediately after and 1 h after the marathon. Plasma concentrations of all amino acids returned to pre-exercise levels by 16 h after exercise. The plasma concentration of the complement anaphylotoxin C5a increased to abnormal levels after the marathon, presumably due to tissue damage activating the complement system. There was also an increase in plasma C-reactive protein 16 h after the marathon. The plasma levels of IL-1 alpha were unaffected by the exercise, while that of IL-2 was increased 16 h after exercise. Plasma IL-6 was increased markedly (approximately 45-fold) immediately after and at 1 h after exercise. Neopterine, a macrophage activation marker, was significantly increased post-exercise. There was a marked leucocytosis immediately after the marathon, which returned to normal 16 h later. At the same time there was a decrease in the number of T-lymphocytes, which was further reduced within 1 h to below pre-exercise levels. Glutamine supplementation, as administered in the second study, did not appear to have an effect upon lymphocyte distribution.

Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.

The endocrinometabolic effects of beclomethasone dipropionate in asthmatic patients.

The endocrinometabolic effects of the aerosol administration of beclomethasone dipropionate (100 microng four times daily) were evaluated in 20 asthmatic patients (11 corticodependent and nine noncorticodependent) during one month. In the noncorticodependent group, aerosol administration of beclomethasone had no statistically significant effect on the results of the glucose tolerance test and the plasma levels of insulin; there was a slight decrease in basal levels of cortisol, but the response of the cortisol level to administration of ACTH remained quite normal. In corticodependent patients, after substitution of aerosol therapy with beclomethasone for the oral therapy with steroids, the depression of adrenal function disappeared, usually quickly (in less than one month), whereas the abnormalities in the results of the glucose tolerance test persisted. Thus, at the dosage used, beclomethasone dipropionate might have minor systemic endocrinometabolic effects.