E. Bernard

Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol

SummaryPharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol were studied. Niflumic acid (250 mg) or analgesic and antipyretic drugs such as paracetamol (500 mg) are often combined with antibiotics to avoid inflammation and pain in acute ear, nose and throat diseases. Pharmacokinetic interactions between these two classes of drugs have been described in experimental models, and exceptionally in humans. The aim of the present investigation was to study the interactions of these two drugs with three antibiotics (amoxicillin 500 mg×2, cefadroxil 500 mg×2, cefixime 200 mg and one placebo capsule) on pharmacodynamic parameters and on rate of killing in the serum of six healthy volunteers receiving the antibiotic associated or not with the product in a randomized cross-over double-blind trial. The bacteria most often involved in sinusitis, bronchitis and otitis media (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) three target diseases for oral cephalosporins and amoxicillin, were chosen for bacteriological study. Blood samples were obtained at 0.25, 0.50, 1, 1.5, 2, 4, 6 and 12 after oral administration of antibiotics alone or associated with the drugs. There was a wash-out period of at least 1 week between the eleven sequences. Antibiotics were measured by two methods: bioassay and high performance liquid chromatography (HPLC). All serum samples obtained at peak level, 4 and 6 h were tested for killing rate. Area under the time kill curve was calculated by the trapezoidal rule method and relative bioactivity in percent was defined as follows: (AUC control — AUC test)/AUC control × 100. No pharmacokinetic interaction was found in the AUC and T1/2 of the plasma concentrations of the antibiotics or associated with the drugs, regardless of dose, as determined by HPLC or microbiological assay. For these β-lactam antibiotics killing rate was found to be time-dependent. Bactericidal activity was improved onH. influenzae when cefixime was associated with niflumic acid and became concentration-dependent. A significant concentration relation was also found with niflumic acid or paracetamol associated with cefixime onStrep. pneumoniae.

Possible prevention of in vitro selection of resistantStreptococcus pneumoniae by beta-lactamase inhibitors

The development of resistance in vitro in five strains ofStreptococcus pneumoniae (3 with full susceptibility and 2 with intermediate susceptibility to penicillin) was investigated by serial passages in the presence of subinhibitory concentrations of amoxicillin and ampicillin. At the end of passaging, MICs of antibiotics for all the strains increased by a factor of four or more, reaching at least intermediate levels. MICs of cephalosporins, ampicillin and amoxicillin increased for almost all variants obtained. Similar results were obtained with amoxicillin plus clavulanic acid at a ratio of 2:1 and at a constant concentration of 2 µg/ml, and with ampicillin plus sulbactam at a ratio 2:1. In contrast, no significant modification of MIC was seen with ampicillin plus sulbactam at a constant concentration of 4 µg/ml sulbactam. These results suggest interaction of sulbactam with penicillin binding proteins as described previously for other bacterial species, and merit further investigation.

Cutaneous infections, good use of antibiotics and diagnostic accuracy.

UNLABELLEDnThe medical dashboard (DB) recording our clinical practices indicated on one hand the use of two different diagnosis terms, acute dermohypodermitis (ADH) or cellulitis, and on the other hand, an important antibiotic prescription heterogeneity. Our aim was to define these two diagnosis groups and to document compliance to our antibiotic therapy protocol.nnnMETHODnADH and cellulitis were selected in our medical DB that records all patient data. Our local antibiotic therapy protocol was designed in April 2009; the prescription of recommended antibiotic agents defined the compliance to recommendations. The patient files indicating non-consensual therapy were analyzed to determine the reasons for inappropriate prescription.nnnRESULTSnThree hundred and four cases of ADH and 82 of cellulitis were diagnosed over 6.5years. ADH was associated with older age (P=0.007), a higher frequency of venous insufficiency (P=0.015), a lower frequency of cancer (P=0.007), and was more often located on lower limbs (P<0.001), compared to cellulitis. The diagnosis of ADH was associated with higher compliance to our antibiotic therapy protocol, compared to cellulitis: 68% versus (vs.) 24%, P<0.001, and after April 2009:xa053% vs. 64%, P=0.033. Among the 162 inappropriate antibiotic prescriptions (42%), 75 were deemed justified after analyzing the patient file, but less frequently for ADH compared to cellulitis: 49% vs. 11,5%, P<0.001.nnnCONCLUSIONnADH presents different clinical characteristics compared to cellulitis. The antibiotic therapy protocol for ADH cannot be applied to cellulitis.

Implication of antibiotic referents in complex bone and joint infections

UNLABELLEDnOne of the main objectives of antibiotic referents in French hospitals is to promote the nationwide antibiotic stewardship program. National guidelines for complex bone and joint infection management (CBJI) issued in 2009, and expert and associated hospital centres were chosen. Our aim was to determine the role of antibiotic referents in CBJI treatment modalities, in 2012.nnnMETHODnA questionnaire was proposed to participants at the seventh national meeting of antibiotic referent in June 2012.nnnRESULTSnNinety-seven questionnaires were completed. Antibiotic referents were mainly infectious diseases doctors working in public hospitals with more than 300 hundreds beds. Twenty-eight units dedicated to CBJI were reported, as well as 35 multidisciplinary team meetings, 57% of which including physicians from both private and public hospitals. The 2009 national recommendations were the reference for 81% of responders, while referring to expert and associated centres was reported by 80%. Patient transfer to a reference center was rare, for both geographic reason and divergent medical and surgical habits. Most antibiotic referents suggested a 6-week course of antibiotic therapy and 12 months of follow-up. Twenty-two percent of the responders participated in morbidity and mortality audits.nnnCONCLUSIONnThe 2009 national guidelines were rapidly taken into account. Their implementation led to more homogeneous clinical practices as reported by antibiotic referents. Reference centres are used for advice but patient transfer to these centres is still rare.

B-01 Évaluation des Pratiques Professionnelles (EPP) et Tableau de Bord (TB) : exemple du Traitement des Pneumonies Aigues Communautaires (PAC)

n n Introduction et objectifsn L’EPP vise à améliorer nos pratiques médicales. Elle comporte 3 phases : la mise en évidence de dysfonctionnements, la proposition de mesures correctives puis l’évaluation des ajustements induits. L’EPP est difficile sans outil pertinent. Notre objectif est d’illustrer l’intérêt d’un TB pour réaliser une EPP.n n n Matériels et méthodesn Notre TB existe depuis Juillet 2005, incluant 24 paramètres dont le diagnostic, l’antibiothérapie et la date d’hospitalisation. Lors de la 1re phase d’EPP, le TB a été utilisé pour étudier les modalités thérapeutiques des PAC, révélant une hétérogénéité d’antibiothérapie non justifiée (Med Mal Inf 2008;9:457-64). La 2e phase a consisté en l’écriture de notre protocole thérapeutique, visant à réduire les prescriptions de fluoroquinolones (FQ) et de céphalosporines de 3e génération (C3G). Nous rapportons ici la 3e phase d’EPP, utilisant le TB pour comparer l’application du protocole sur 2 périodes : avant (d’octobre à janvier 2005 et 2006) et après (d’octobre 2008 au 20 février 2009) sa mise en place. L’utilisation de plusieurs lignes thérapeutiques, suggérant l’inadéquation de l’antibiothérapie initiale, a été répertoriée.n n n Résultatsn Les PAC représentaient 178 hospitalisations avant l’application du protocole, et 81 après. Le taux de conformité avec le protocole était respectivement de 101/178 (57 %), et de 52/81 (64 %). Le nombre d’antibiothérapies contenant des FQ et/ou des C3G de manière inadéquate était de 45/178 (25 %) durant la première période, et de 19/81 (23 %) durant la seconde période. Plusieurs lignes thérapeutiques étaient utilisées 28/178 fois (16 %) et 12/81 fois (15 %). La durée d’hospitalisation était respectivement de 9±5 et 8±5 jours, une évolution défavorable étant observée dans 8/178 (5 %) et 1/81 cas (1,2 %).n n n Conclusionn Un TB permet l’exécution rapide de 2 des 3 phases de l’EPP. Nos résultats suggèrent une appropriation partielle de notre protocole, la réduction des FQ et des C3G apparaissant sans impact sur la morbi-mortalité.n n