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Abstract: Aims of the study: This study examines the activity of doripenem, a new carbapenem compound compared with amoxicillin-clavulanic acid, piperacillin+tazobactam, imipenem, clindamycin and metronidazole against 316 anaerobes. Methods: Inoculum preparation and agar dilution method were performed according to the CLSI method for anaerobes (M11A7). Results: At a concentration of 4μg/ml doripenem and imipenem (IMP) inhibited 122 (96 %) and 126 (99 %) strains of the Bacteroides fragilis group, respectively. In contrast, doripenem appeared more potent than IMP against Gram-positive anaerobes inhibiting at the same concentration of 4μg/ml 145/145 strains (100 %) versus 115/145 for IMP (79.3 %). Against 316 anaerobic strains, the carbapenem doripenem had an MIC50 of 0.25μg/ml and an MIC90 of 2μg/ml. Results were similar to those for imipenem (MIC50 of 0.125μg/ml and MIC90 of 4μg/ml). If we consider the resistant breakpoints of the two carbapenems as defined by EUCAST, the resistance rate for doripenem (MIC>4μg/ml) 1.6 % is similar to that of imipenem (MIC>8μg/ml) 1.3 %. Conclusion: Thus independently of the PK/PD parameters the two carbapenems demonstrated very close activity; doripenem was more potent on Gram-positive anaerobes and slightly less potent against Gram-negative anaerobes mainly the B. fragilis group. Further clinical studies are needed to assess its usefulness in patients. [Copyright &y& Elsevier]

Abstract: Ertapenem activity in vitro was compared with that of nine reference antibiotics against 337 anaerobes by determining minimal inhibition concentrations (MICs). Amongst 246 Gram-negative anaerobes, 4, 8, 3, 4, 7, 2 and 52 strains showed resistance to ertapenem, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoxitin, imipenem and clindamycin, respectively, and all strains were inhibited by metronidazole. Ertapenem MIC50 values were 0.5, 0.25, 0.06 and ≤0.03mg/L for the Bacteroides fragilis group, Prevotella spp., fusobacteria and Gram-positive cocci, respectively. Overall resistance rates were 2.1%, 51.3%, 2.4%, 1.2%, 1.5%, 7.1%, 0.6%, 22% and 1.5% for ertapenem, amoxicillin, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoxitin, imipenem, clindamycin and metronidazole, respectively. Ertapenem showed a broad spectrum and good activity against anaerobes. [Copyright &y& Elsevier]

The activity of gatifloxacin, a new fluoroquinolone derivative, was compared with the activities of ciprofloxacin, levofloxacin, amoxicillin, amoxicillin–clavulanate, imipenem, clindamycin and metronidazole against 204 anaerobes isolated from clinical specimens, by MIC determination, using the reference agar dilution method. When determining the overall activity against anaerobes, the MIC50/90 (mg/L) values were amoxicillin 16/>64, amoxicillin–clavulanate 0.125/1, imipenem 0.25/0.5, clindamycin 0.5/>256, metronidazole 1/8, ciprofloxacin 2/32, levofloxacin 1/8 and gatifloxacin 0.5/4. The broad in vitro spectrum of gatifloxacin is promising for the treatment of mixed anaerobic infections, especially those of the respiratory tract, ear, sinus, skin and soft tissues, and bite wounds. These data suggest that gatifloxacin may have a clinical role in the treatment of infections in which anaerobic pathogens are involved. [ABSTRACT FROM AUTHOR]

This study looked for β-lactamase production in 100 Provotella isolates. MICs were determined for amoxycillin, ticarcillin, amoxycillin+clavulanate, cephalothin, cefuroxime, cefixime, cefpodoxime and cefotaxime using the reference agar dilution method (standard M11 A4, NCCLS). Beta-lactamase activity was detected in 58 of the 100 isolates, 24 of 46 black-pigmented Provotella and 34 of 54 non-pigmented Provotella. All β-lactamase-negative strains were susceptible to all β-lactam antibiotics with the exception of cefuroxime and cefixime. Overall, resistance rates of Provotella strains were lower for ticarcillin (8%) and celefotaxime (12%) than for the other cephalosporins. All Provotella isolates were susceptible to amoxyillin and were all inhibited by 2 mg/l or less amoxcillin. [Copyright &y& Elsevier]

The in vitro activity of moxifloxacin was compared to that of ofloxacin, ciprofloxacin, clindamycin, metronidazole and 6 β-lactams (amoxicillin, amoxicillin + clavulanic acid, ticarcillin, ticarcillin + clavulanic acid, cefotetan and imipenem) for a selected group of anaerobes isolated from human clinical samples. MICs were determined by the reference M 11 A4 agar dilution method of the NCCLS. Moxifloxacin demonstrated good activity against the 76 strains of the Bacteroides fragilis group ; MIC50 was 0.5 mg/l. MIC50s of imipenem and metronidazole were 0.125 mg/l, and 0.5 mg/l, respectively. All strains of Porphyromonas, Prevotella, Fusobacterium and Peptostreptococcus were inhibited by moxifloxacin concentrations of ≤ 1mg/l.Out of 159 anaerobes, moxifloxacin inhibited 93.7, 94.9 and 98% of the strains investigated at concentrations of 1, 2 and 4 mg/l respectively. Moxifloxacin, unlike other fluoroquinolones, demonstrated high activity against strains of the B. fragilis group and Clostridum sp. It was more potent than ofloxacin and ciprofloxacin against Gram positive rods and anaerobic cocci.Given the broad spectrum of moxifloxacin against anaerobes, future clinical studies will be required to determine the role of this agent for the treatment of anaerobic infections. [Copyright &y& Elsevier]

Clin Microbiol Infect 2010; 16: 470–472 Bacterial vaginosis is a polymicrobial syndrome. The most important marker for bacterial vaginosis is the presence of Gardnerella vaginalis and Atopobium vaginae. In this study, the in vitro susceptibilities to metronidazole and secnidazole of 16 strains of A. vaginae were tested with the agar dilution method. We observed an MIC range for metronidazole of 4–64 mg/L (MIC50, 8 mg/L; MIC90, 32 mg/L) and an MIC range for secnidazole of 4–128 mg/L (MIC50, 16 mg/L; MIC90, 64 mg/L). According to these findings, we can conclude that the activity of secnidazole is similar to that of metronidazole. [ABSTRACT FROM AUTHOR]

Abstract: Gram-positive anaerobic cocci (GPAC) are a heterogeneous group of microorganisms frequently isolated from local and systemic infections. In this study, the antimicrobial susceptibilities of clinical strains isolated in 10 European countries were investigated. After identification of 299 GPAC to species level, the minimum inhibitory concentrations of penicillin, imipenem, clindamycin, metronidazole, vancomycin and linezolid were determined by the agar dilution method according to the Clinical and Laboratory Standards Institute. The majority of isolates were identified as Finegoldia magna and Parvimonas micra (formerly Peptostreptococcus micros), isolated from skin and soft tissue infections. All isolates were susceptible to imipenem, metronidazole, vancomycin and linezolid. Twenty-one isolates (7%) were resistant to penicillin (n =13) and/or to clindamycin (n =12). Four isolates were resistant to both agents. The majority of resistant isolates were identified as F. magna and originated from blood, abscesses and soft tissue infections. [Copyright &y& Elsevier]

The aim of this study was to investigate porin absence or deficiency in two Bacteroides thetaiotaomicron strains resistant to amoxicillin combined with clavulanic acid. Their outer membrane protein (OMP) extracts and those of two susceptible strains were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and compared to detect differences between the strains. A protein band of interest at around 70 kDa electro-eluted for each strain, was tested in a liposome swelling assay. A decrease in initial absorbency was noted for the two susceptible strains but not for the two resistant strains. The liposome swelling of the two susceptible strains was directly visualized by photon microscopy and then photographed. This suggested a B. thetaiotaomicron porin of around 70 kDa could take part in resistance to β-lactams. [Copyright &y& Elsevier]

Clin Microbiol Infect 2012; 18: 1117-1125 Abstract All organisms usually isolated in our laboratory are now routinely identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using the Andromas software. The aim of this study was to describe the use of this strategy in a routine clinical microbiology laboratory. The microorganisms identified included bacteria, mycobacteria, yeasts and Aspergillus spp. isolated on solid media or extracted directly from blood cultures. MALDI-TOF MS was performed on 2665 bacteria isolated on solid media, corresponding to all bacteria isolated during this period except Escherichia coli grown on chromogenic media. All acquisitions were performed without extraction. After a single acquisition, 93.1% of bacteria grown on solid media were correctly identified. When the first acquisition was not contributory, a second acquisition was performed either the same day or the next day. After two acquisitions, the rate of bacteria identified increased to 99.2%. The failures reported on 21 strains were due to an unknown profile attributed to new species (9) or an insufficient quality of the spectrum (12). MALDI-TOF MS has been applied to 162 positive blood cultures. The identification rate was 91.4%. All mycobacteria isolated during this period (22) were correctly identified by MALDI-TOF MS without any extraction. For 96.3% and 92.2% of yeasts and Aspergillus spp., respectively, the identification was obtained with a single acquisition. After a second acquisition, the overall identification rate was 98.8% for yeasts (160/162) and 98.4% (63/64) for Aspergillus spp. In conclusion, the MALDI-TOF MS strategy used in this work allows a rapid and efficient identification of all microorganisms isolated routinely. [ABSTRACT FROM AUTHOR]

Both linezolid and cotrimoxazole are antibiotics that are well suited for oral therapy of bone and joint infections (BJI) caused by otherwise resistant Gram-positive cocci (GPC) (resistance to fluoroquinolones, maccolides, betalactamines). However, in this context, no data are currently available regarding the safety and tolerance of these antibiotics in combination with rifampicin. The objective of this study was to compare the efficacy and safety of a combination of rifampicin and linezolid (RLC) with those of a combination of rifampicin and cotrimoxazole (RCC) in the treatment of BJI. Between February 2002 and December 2006, 56 adult patients (RLC, n = 28; RCC, n = 28), including 36 with infected orthopaedic devices (RLC, n = 18; RCC, n = 18) and 20 with chronic osteomyelitis (RLC, n = 10; RCC, n = 10), were found to be eligible for inclusion in this study. Patients who discontinued antibiotic therapy within 4 weeks of commencing treatment were considered to represent cases of treatment failure and were excluded. Rates of occurrence of adverse effects were similar in the two groups, at 42.9% in the RLC group and 46.4% in the RCC group (p = 1.00), and led to treatment discontinuation in four (14.3%) RLC and six (21.4%) RCC patients. Cure rates were found to be similar in the two groups (RLC, 89.3%, RCC, 78.6%; p = 0.47). Prolonged oral RLC and RCC therapy were found to be equally effective in treating patients with BJI caused by resistant GPC, including patients with infected orthopaedic devices. However, the lower cost of cotrimoxazole compared with linezolid renders RCC an attractive treatment alternative to RLC. Further larger clinical studies are warranted to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Abstract: A case of Salmonella paratyphi A infection was diagnosed late in a patient treated for febrile pneumonia after his returning from India. This case was remarkable in two aspects: first, it illustrated the reemergence of S.paratyphi A infections in people having traveled to India, with increasing fluoroquinolone resistance, and second the difficulty of diagnosing this disease, since the patient was initially treated for pneumonia and flu-like syndrome. Salmonella typhi or paratyphi infections should be evoked in case of persistent fever in patients having traveled to endemic areas, even if digestive signs are absent. Furthermore, choosing an empiric antibiotic treatment with fluoroquinolones could lead to treatment failure if the patient traveled in a country where fluoroquinolone resistance is high, as in Asia and especially in India. [Copyright &y& Elsevier]

Abstract: Material and method: Using an agar reference method (Norma M11-A5, National Committee for Clinical and Laboratory Standards) the minimal inhibitory concentrations of nine antibiotics were determined for 376 anaerobic strains. The following strains were investigated: 254 Bacteroides fragilis group (including 143 B. fragilis), 122 other gram-negative anaerobes (Bacteroides spp., Prevotella, Fusobacterium, Porphyromonas, Suterella, Desulfomonas, Veillonella). Results: In the B. fragilis group resistance rates were: coamoxyclav 2.8%, ticarcillin 27.5%, ticarcillin–clavulanic acid 1.9%, piperacillin–tazobactam 1.9%, cefoxitin 6.2%, imipenem 0.8%, clindamycin 28.3%, respectively. Based on previous studies, resistance to imipenem remained low in 2003 and was only observed for B. fragilis. Resistance to clindamycin was maintained around 25%. No metronidazole resistance was observed, but decreased susceptibility was found for B. fragilis, B. merdae and Prevotella, as in 4.3% of gram-negative anaerobes. Discussion: This study confirms the high resistance rate of gram-negative anaerobes to clindamycin, the efficient activity of imipenem, β-lactam/β-lactamase inhibitor combinations and metronidazole. However, reduced metronidazole susceptibility seems to be increasing. [Copyright &y& Elsevier]

Abstract: Study aims: The aim was to evaluate the in vitro effects of amoxicillin and its combination with clavulanic acid, two β-lactams intravenously injected, on the oxidative metabolism of polymorphonuclear neutrophils. These cells play the major role in the “respiratory burst” as they produce superoxide anion to kill the infectious agent. An activation of this process by the injected antibiotics could enhance the bactericidal action or explain some of adverse effects. Materials and methods: Two models were used to estimate the O2 – amounts produced in the presence of the antimicrobial agents. In the cellular model, O2 – was generated by neutrophils artificially stimulated or not (separated by a gradient centrifugation through Histopaque 1077). In the acellular model, O2 – was produced by the xanthine–xanthine oxidase system. O2 – was measured by spectrophotometry using the ferricytochrome C reduction. Results: The O2 – production by polymorphonuclear neutrophils was increased when both antibiotics were added to the reaction mixture. A significant activation of the cell oxidative metabolism was observed with amoxicillin using various stimulating agents, that was higher without stimulation and lower when amoxicillin and clavulanic acid were associated. Conclusion: Amoxicillin could either activate polymorphonuclear neutrophils NADPH-oxidase or cause its activation by a membrane effect, or interfere with the zymosan activation way. It could then be supposed that this antimicrobial agent intensified the bactericidal effects. [Copyright &y& Elsevier]

Introduction: Le traitement des IOA à cocci Gram positif (CGP) résistants peut nécessiter le recours à certaines molécules alternatives comme le linézolide ou le cotrimoxazole. Objectif: Comparer l’efficacité et la tolérance des associations RL et RC dans le traitement des IOA. Méthodes: Les dossiers de 56 patients adultes traités par voie orale par les associations RL (n = 29) et RC (n = 27) pendant plus de 4 semaines pour une IOA ont été analysés en termes de succès clinique et de tolérance. Résultats: 34 patients avaient une infection sur matériel orthopédique (RL = 18, RC = 16), et 22 une ostéomyélite chronique (RL = 11, RC = 11). Les souches de Staphylococcus spp résistants à la méticilline étaient prédominantes (RL = 53,3 %, RC = 42,9 %). Les durées moyennes de traitement étaient de 17,8 ± 7,5 et 16,2 ± 10,8 semaines pour les groupes RL et RC respectivement. Les patients bénéficiaient d’une antibiothérapie parentérale pendant 6-8 jours en hospitalisation, puis d’un relais oral par RL ou RC. La fréquence des effets indésirables (EI) était similaire entre les 2 groupes (RL = 44,8 %, RC = 40,7 %), nécessitant des arrêts de traitement pour 5 patients (17,2 %) avec RL (anémie = 4, neuropathie périphérique = 1) et 5 patients (18,5 %) avec RC (rash cutané = 2, EI digestifs = 3). Les taux de guérison étaient similaires entre les 2 groupes [RL : 89,6 % (26/29), RC : 88,9 % (24/27)]. Conclusion: RL et RC sont des combinaisons efficaces dans le traitement prolongé des IOA à CGP, y compris sur matériel orthopédique. Cependant, le faible coût du cotrimoxazole (1 €/j) comparé à celui du linézolide (124 €/j) en fait une alternative plus attractive. Ces résultats nécessitent d’être confirmés par des études de plus grande ampleur. [Copyright &y& Elsevier]

Objectif de l’étude: Analyse de la morbi-mortalité précoce en cas d’IPV dans 2 centres. Méthodes: L’IPV était définie par une collection péri-prothétique au TDM et une bactériologie positive. Résultats: 60 pts (56 H, 6 F) d’âge moyen 67 ± 11ans présentant 62 IPV ont été inclus. Les co-morbidités étaient l’HTA (79 %), une cardiopathie ischémique (57 %), l’obésité (56 %), l’insuffisance rénale chronique (37 %), le diabète (34 %), l’immunodépression (8 %), la dénutrition (6,3 %). L’IPV était aortique (n = 27), infra-inguinale (n = 35). Un quart des IPV avaient eu un geste de désobstruction. Les prélèvements (intra-opératoires-hémocultures) ont isolé MSSA (n = 13), SARM (n = 6), SCN (n = 10), Streptococcus sp. (n = 3), Enterococcus sp. (n = 3), enterobactéries (n = 24), Pseudomonas sp. (n = 5), anaérobies (n = 4), Candida sp. (n = 2). Un quart avait une infection polymicrobienne et 2/3 une IPV précoce. Les cocci à gram positif prédominaient dans les IPV infra-inguinales. Le traitement a consisté en une autogreffe (n = 10), allogreffe (n = 7), remplacement prothétique (n = 10), un drainage (n = 23), une ablation définitive (n = 2). Dix pts ont été traités médicalement. Le taux de complications était plus élevé en cas d’IPV aortique avec un taux de choc septique significativement plus élevé de même que le recours à la ventilation et à la dialyse. La mortalité globale était de 11,3 % à 3 mois (pas de différence significative). Conclusion: Les IPV nécessitent une prise en charge multidisciplinaire entraînée du fait de la morbi-mortalité précoce importante. Le type de pontage ne permet pas de cibler l’antibiothérapie. [Copyright &y& Elsevier]

Introduction: La bonne biodisponibilité orale et bonne pénétration osseuse du LZD semblent attractif pour le traitement des IOA. Son utilisation est cependant limitée par sa toxicité hématologique dose-dépendante et sa toxicité neurologique. Objectif: comparer rétrospectivement les données hématologiques des patients (pts) traités pour une IOA pendant > 4 s par LZD-RIF ou par LZD seul ou en association avec une autre molécule que RIF. Méthodes: L’anémie était définie par un taux d’hémoglobine < 9 g/dl, la thrombopénie par un taux de plaquettes < 100 000/mm3 (surveillance hebdomadaire). Résultats: 94 patients d’âge moyen 53,5 ans (± 17,18-94) traités pour une IOA dont 67 % avec matériel étaient inclus. Les co-morbidités étaient le diabète (27 %), l’alcoolisme (9,6 %) et l’insuffisance rénale chronique (6,4 %). 43 patients (44,8 %) ont reçu LZD-RIF, 25 (26,6 %) le LZD seul et 28 patients (29,7 %) une autre association avec le LZD. 21 patients (22,3 %) avaient une infection polymicrobienne. SCN était le plus souvent isolée (38 %) dans les prélèvements intra-opératoires, suivi de S. aureus (31 %), des BG+ (17 %), BGN (10 %) et des anaérobies (4 %). Les caractéristiques des patients traités par LZD-RIF ou par un autre traitement comprenant LZD étaient identiques. 5 patients traités par LZD-RIF ont présenté une anémie (13,4 ± 8,7 s) vs 22 patients (9,5 ± 4,3 s) ayant reçu tout autre traitement comprenant LZD (p = 0,001). LZD a été stoppé chez 21 patients. Quinze ont été transfusés. Conclusion: L’association de la RIF au LZD en traitement prolongé pour une IOA est associée à une réduction de l’incidence de l’anémie. Ces résultats sont à rapprocher de l’augmentation de la clearance digestive du LZD secondaire à la production d’une glycoprotéine P transmembranaire sous l’action de RIF. [Copyright &y& Elsevier]