In vitro activity and in vivo efficacy of tigecycline alone and in combination with daptomycin and rifampin against Gram-positive cocci isolated from surgical wound infection

The aim of this work was to determine the in vitro activity of tigecycline and its bactericidal effect for a large number of Gram-positive cocci, as well as to investigate its in vitro interaction with six clinically used antibiotics. In vivo, a wound model was established through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 10(7) colony-forming units (CFU) of Staphylococcus aureus or Enterococcus faecalis. For each bacterial strain, the study included an infected or non-infected group that did not receive any treatment, three groups singly treated with tigecycline, rifampin, and daptomycin, and two groups that received tigecycline treatment plus rifampin or daptomycin. In the in vitro studies, tigecycline, daptomycin, and teicoplanin were active against all of the 48 Gram-positive isolates. The combination of tigecycline with rifampicin and daptomycin was synergistic against S. aureus and Enterococcus spp. In the in vivo studies, all groups treated with single drugs showed statistically significant results compared to the control group. The two groups treated with a combination of drugs showed the highest antimicrobial efficacy. In conclusion, our results suggested a strong activity of tigecycline alone and in combination with other antimicrobial agents against multi-resistant Gram-positive organisms isolated from wound infections.     

In vitro activities of quinupristin/dalfopristin and eight other antimicrobial agents against 360 clinical isolates from Korea

The emergence of multi-drug resistant gram-positive cocci such as methicillin-resistant (MR) staphylococci, vancomycin-resistant (VR) enterococci, and vancomycin-intermediate resistant S. aureus (VISA) has given new urgency to the development of new antimicrobial agents. One of these is quinupristin/dalfopristin (Q/D). We decided to determine the susceptibility of gram-positive cocci isolated at two university hospitals in Seoul to Q/D and compare the results with eight other antimicrobial agents. We investigated 120 isolates of S. aureus including 49 MRSAs and one VISA, 120 isolates of coagulase negative staphylococci (CNS), 64 E. faecalis and 56 E. faecium, including seven strains of VR E. faecium. Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) for several antimicrobials, including vancomycin and Q/D, were determined by broth microdilution. All S. aureus including VISA were susceptible to Q/D. Q/D MIC90 for both methicillin-susceptible S. aureus (MSSA) and MRSA was 0.25 g/mL. 49 (87.5%) of 56 E. faecium including six of seven VR E. faecium were susceptible to Q/D. E. faecalis were not susceptible to Q/D (only 1.5% susceptible), but were inhibited by ampicillin (94% susceptible) or vancomycin (95%). CNS was susceptible to Q/D (96% susceptible) and vancomycin (100% susceptible). One of 38 staphylococci and two of 17 E. faecium were tolerant to Q/D. In conclusion, Q/D showed excellent activity against all species of gram-positive cocci including MRSA, VISA, and VR E. faecium except E. faecalis, and may provide a valuable option for the treatment of infections caused by these emerging nosocomial pathogens of gram-positive cocci.     

In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium

We assessed the in vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin (QD) against a contemporary challenge panel of 88 staphylococcal and 90 enterococcal isolates. The staphylococci selected included vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant S. aureus, and coagulasenegative staphylococci. Enterococcal isolates included vancomycin-resistant Enterococcus faecium (VREF) containing either vanA, vanB1, or vanD. The MICs of daptomycin, linezolid, and QD were determined using commercial broth microdilution panels. All three VISA isolates were susceptible to daptomycin, linezolid, and QD. QD was the most active agent against staphylococcal isolates (MIC50 < or = 0.5 microg/ml and MIC90 = 1 microg/ml), including those with decreased susceptibility to vancomycin. QD was also the most active agent against VREF (MIC90 < or = 0.5 microg/ml). No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD. Daptomycin was the most effective against E. faecalis. On the basis of manufacturer-suggested interpretive criteria, 92% of isolates were susceptible (MIC90 = 4 microg/ml). All isolates tested were susceptible to at least one antimicrobial agent for which interpretive criteria have been defined. Population analysis of three S. aureus isolates for which the daptomycin MICs were 8 microg/ml showed a pattern of homogeneous resistance.     

Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci

BAL9141 has been reported to have inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), many enterococci, and streptococci with various resistant patterns. BAL9141 potency was assessed by time–kill curves alone or with subinhibitory concentrations of gentamicin (MIC/4). BAL9141 exhibited bactericidal activity alone against all the streptococci and staphylococci. Among ampicillin-susceptible enterococci, BAL9141 was bactericidal against some strains, but no BAL9141 inhibition was observed of ampicillin-resistant Enterococcus faecium . The activity of BAL9141 with gentamicin was slightly enhanced (not synergy) or indifferent against staphylococci. BAL9141 demonstrated bactericidal action alone against Enterococcus faecalis and some E. faecium strains (− 4.8 to −6.0 log₁₀ CFU/mL), but static effects were also noted. Drug interactions with gentamicin showed early synergy (4–8 h) for all enterococci, and indifference or synergy at 24 h (no antagonism). BAL9141 (≤8 mg/L) showed promising bactericidal activity alone and synergy with gentamicin against some of the vancomycin-resistant enterococci tested.     

Antimicrobial susceptibility of Gram-positive bacteria isolated from European medical centres: results of the Daptomycin Surveillance Programme (2002–2004)

The antimicrobial susceptibility patterns of 9322 contemporary (2002-2004) gram-positive bacterial isolates collected from 31 medical centres in 14 countries in Europe were evaluated by broth microdilution methods according to CLSI guidelines. The isolates collected comprised Staphylococcus aureus (4842 isolates), coagulase-negative staphylococci (CoNS; 1942 isolates), Enterococcus faecalis (1147 isolates), Enterococcus faecium (391 isolates), beta-haemolytic streptococci (660 isolates) and viridans group streptococci (340 isolates). The organisms were tested against daptomycin and more than 20 comparator agents in Mueller-Hinton broth, supplemented with calcium to 50 mg/L when testing daptomycin. Overall, methicillin (oxacillin) resistance rates were 26.7% and 77.0% for S. aureus (MRSA) and CoNS, respectively, and the vancomycin resistance rate among enterococci was 6.1%. MRSA rates varied from 0.6% in Sweden to 40.2-43.0% in Belgium, Greece, Ireland, the UK and Israel, and VRE rates varied from 0% in Switzerland to 21.2% in Ireland. More than 99.9% of isolates tested were considered susceptible to daptomycin according to breakpoints established by the United States Food and Drug Administration and the CLSI. Daptomycin was active against all gram-positive species, with the highest MIC being 2, 8, 0.5 and 2 mg/L for staphylococci, enterococci, beta-haemolytic streptococci and viridans group streptococci, respectively. Daptomycin activity was not influenced adversely by resistance to other agents among staphylococci or enterococci. This novel lipopeptide (daptomycin) appears to be an excellent alternative therapeutic option for serious infections caused by multidrug-resistant gram-positive organisms isolated in Europe.     

1999-2006年北京朝阳医院革兰阳性球菌耐药性分析

目的 探讨北京朝阳医院1999-2006年临床分离的革兰阳性球菌的耐药变迁,以指导临床合理使用抗菌药物.方法 采用MIC法进行抗菌药物敏感性试验,以WHONET5.3软件分析数据.结果 6192株临床分离的革兰阳性球菌中,前4位病原菌依次为凝同酶阴性葡萄球菌、金黄葡萄球菌、粪肠球菌、屎肠球菌.耐甲氧西林金黄葡萄球菌(MRSA)、耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)平均检出率分别为88.4%、86.9%,金黄葡萄球菌对青霉素、氨苄西林耐药率最高,8年间始终保持在90.0%以上.未发现对万古霉素耐药或中介的金黄葡萄球菌或凝固酶阴性葡萄球菌.2003年首次分离耐万古霉素肠球菌(VRE),至2006年共发现30株VRE,其中13株为耐万古霉索粪肠球菌,均为VanB基因型;17株为耐万古霉素屎肠球菌,均为VanA基因型,耐万古霉素屎肠球菌分离率呈上升趋势.对于粪肠球菌活性最高的是万古霉素、氨苄西林、青霉素,敏感率分别为98.7%、95.7%、85.6%.但是青霉素敏感性略有下降,从94.3%降至84.6%.克林霉素的耐药率8年中始终维持在99.0%以上.屎肠球菌对红霉素、克林霉素的耐药率均达95.0%以上,对青霉素、氨苄西林、环丙沙星的耐药率均大于90.0%.屎肠球菌最为敏感的药物是万古霉素,对四环素敏感性出现上升的趋势,从27.8%升到82.6%.结论 万古霉素对临床常见的革兰阳性菌保持很高的活性,发现30株耐万古霉素的肠球菌.     

Assessment of two commercial susceptibility test methods for determination of daptomycin MICs

Daptomycin is a lipopeptide antibiotic with activity against several important gram-positive bacterial pathogens, including drug-resistant staphylococci and enterococci. Because the mechanism of action of daptomycin is calcium-dependent depolarization of the cell membrane, susceptibility testing requires medium supplemented with a physiological level of calcium. This study assessed two Food and Drug Administration-cleared commercial test devices for determination of daptomycin MICs, Etest and JustOne. A collection of 220 selected isolates, including Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, E. faecium, E. avium, E. durans, E. casseliflavus, and E. gallinarum, were tested by both methods. Included in the collection were 22 S. aureus and 14 Enterococcus sp. isolates that were recovered from patients and were nonsusceptible on the basis of the daptomycin MICs. As the reference method for comparison, all isolates were tested by the Clinical and Laboratory Standards Institute broth microdilution method incorporating cation-adjusted Mueller-Hinton broth with 50 microg/ml calcium. Daptomycin MICs agreed, within 1 twofold dilution, for 97% of the isolates by Etest and for 100% by JustOne. However, daptomycin MICs determined by Etest were 1 dilution lower than the reference MICs for 65% of the Enterococcus sp. isolates tested. This resulted in 28.5% very major (VM) errors (4/14) with enterococci (all E. faecium) but none (0/22) with staphylococci. Use of JustOne yielded MICs that were 1 dilution lower than the reference MICs for 69% of the staphylococci and 25% of the enterococci. This resulted in 13.6% VM errors (3/22) with staphylococci and 14.3% VM errors (2/14) with enterococci. The manufacturer-recommended JustOne inoculum preparation resulted in mean colony counts of only 5 x 10(4) to 1 x 10(5) CFU/ml in the wells of the strip. Increasing the inoculum to 3 x 10(5) to 4 x 10(5) CFU/ml eliminated two of five VM errors upon retesting. No major interpretive errors occurred with either device. In summary, daptomycin MICs generated by the Etest or JustOne method generally agreed within 1 dilution of the reference daptomycin MICs. However, both devices produced slightly lower MICs that resulted in some VM errors.     

临床分离屎肠球菌和粪肠球菌敏感性对比分析

目的 了解医院临床分离的145株屎肠球菌和86株粪肠球菌的耐药性.方法 采用法国梅里埃公司的VITEK2COMPACT全自动微生物分析仪对菌株进行鉴定和抗菌药物敏感性检测.结果 屎肠球菌和粪肠球菌主要来源于尿液（48.92％）,其次为血液（12.99％）.屎肠球菌和粪肠球菌对万古霉素、利奈唑烷和替加环素的敏感率均为100％;屎肠球菌除对喹奴普汀/达福普汀和四环素的敏感率显著高于粪肠球菌外,对呋喃妥因、氨苄西林、青霉素G、莫西沙星、环丙沙星、左氧氟沙星的敏感率均显著低于粪肠球菌.结论 屎肠球菌和粪肠球菌对抗菌药物的敏感性存在差异,临床应根据抗菌药物敏感性特征结合种间耐药性差异制定治疗方案.目前万古霉素、利奈唑烷,替加环素为治疗屎肠球菌和粪肠球菌感染的最有效抗菌药物.     

Isolation and chemical characterization of a capsular polysaccharide antigen shared by clinical isolates of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium

Enterococci are a common cause of serious infections, especially in newborns, severely immunocompromised patients, and patients requiring intensive care. To characterize enterococcal surface antigens that are targets of opsonic antibodies, rabbits were immunized with various gentamicin-killed Enterococcus faecalis strains, and immune sera were tested in an opsonophagocytic assay against a selection of clinical isolates. Serum raised against one strain killed the homologous strain (12030) at a dilution of 1:5,120 and mediated opsonic killing of 33% of all strains tested. In addition, this serum killed two (28%) of seven vancomycin-resistant Enterococcus faecium strains. Adsorption of sera with the homologous strain eliminated killing activity. The adsorbing antigens were resistant to treatment with proteinase K and to boiling for 1 h, but were susceptible to treatment with sodium periodate, indicating that the antigen inducing opsonic activity is a polysaccharide. Antibodies in immune rabbit sera reacted with a capsule-like structure visualized by electron microscopy both on the homologous E. faecalis strain and on a vancomycin-resistant E. faecium strain. The capsular polysaccharides from E. faecalis 12030 and E. faecium 838970 were purified, and chemical and structural analyses indicated they were identical glycerol teichoic acid-like molecules with a carbohydrate backbone structure of 6-alpha-D-glucose-1-2 glycerol-3-PO4 with substitution on carbon 2 of the glucose with an alpha-2-1-D-glucose residue. The purified antigen adsorbed opsonic killing activity from immune rabbit sera and elicited high titers of antibodies (when used to immunize rabbits) that both mediated opsonic killing of bacteria and bound to a capsule-like structure visualized by electron microscopy. These results indicate that approximately one-third of a sample of 15 E. faecalis strains and 7 vancomycin-resistant E. faecium strains possess shared capsular polysaccharides that are targets of opsonophagocytic antibodies and therefore are potential vaccine candidates.     

New antimicrobial agents as therapy for resistant gram-positive cocci

Vancomycin- and methicillin-resistant gram-positive cocci have emerged as an increasingly problematic cause of hospital-acquired infections. We conducted a literature review of newer antibiotics with activity against vancomycin-resistant and methicillin-resistant gram-positive cocci. Quinupristin/dalfopristin, linezolid, daptomycin, and tigecycline have in vitro activity for methicillin-resistant staphylococci and are superior to vancomycin for vancomycin-resistant isolates. Dalbavancin, telavancin, and oritavancin are new glycopeptides that have superior pharmacodynamic properties compared to vancomycin. We review the antibacterial spectrum, clinical indications and contraindications, pharmacologic properties, and adverse events associated with each of these agents. Daptomycin has rapid bactericidal activity for Staphylococcus aureus and is approved for use in bacteremia and right-sided endocarditis. Linezolid is comparable to vancomycin in patients with methicillin-resistant S. aureus (MRSA) pneumonia and has pharmacoeconomic advantages given its oral formulation. Quinupristin/dalfopristin is the drug of choice for vancomycin-resistant Enterococcus faecium infections but has no activity against Enterococcus faecalis. Tigecycline has activity against both enterococcus species and MRSA; it is also active against Enterobacteriaceae and anaerobes which allows for use in intra-abdominal and diabetic foot infections. A review of numerous in vitro and animal model studies shows that interaction between these newer agents and other antistaphylococcal agents for S. aureus are usually indifferent (additive).     

In vitro activity of teicoplanin against gram-positive cocci

The glycopeptide susceptibility of 443 clinical isolates of gram-positive cocci collected from nine general hospitals in 1996 was determined according to the recommendations of the CA-SFM (the Antibiogram Committee of the French Society for Microbiology). In total, 234 isolates of Staphylococcus aureus, 84 isolates of coagulase-negative staphylococci (CNS), 98 enterococci and 27 streptococci were collected. The mecA gene confirming resistance to methicillin was found in 42.7% of S. aureus isolates and 51.2% of CNS isolates. No resistance to teicoplanin and vancomycin was found in S. aureus but four isolates of CNS had an MIC of teicoplanin > or = 8 mg/L. All isolates of Enterococcus faecalis tested were susceptible to both glycopeptides. This study confirms that teicoplanin has a very good in vitro activity against gram-positive cocci, isolated in France from nosocomial infections.     

Antibacterial activity of Australian plant extracts against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE)

Ethanolic extracts of five traditional Australian medicinal plants, previously shown to display antibacterial activity against laboratory strains of the Gram positive bacteria Staphylococcus aureus and Enterococcus faecalis, were investigated for their abilities to inhibit clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Using plate-hole diffusion assays, the following results were obtained: (a) extract from the leaves of Eremophila alternifolia (Myoporaceae) showed activity against MRSA; (b) extract from the leaves of Acacia kempeana (Mimosaceae) showed incomplete inhibition of VRE; (c) extracts from the leaves of Amyema quandong (Loranthaceae) and Eremophila duttonii (Myoporaceae) were active against both types of bacteria; (d) extract from the stem base of Lepidosperma viscidum (Cyperaceae) was active against MRSA and exhibited incomplete inhibition of VRE. All active extracts were evaluated using time-kill assays. Most of the extracts showed bactericidal effects and reduced the number of viable cells by 4-6 logs within four hours, while the extracts from Acacia kempeana leaves and Lepidosperma viscidum stem base exhibited bacteriostatic activity against VRE. The extract from the leaves of Eremophila duttonii was the most active and reduced the number of viable cells of MRSA and VRE to undetectable levels within 1 hour.     

Bactericidal activity of daptomycin against vancomycin-resistantEnterococcus faecium in an in vitro pharmacokinetic model

A dynamic in vitro model was used to determine the killing kinetics of daptomycin against 15 vancomycin-resistant clinical isolates ofEnterococcus faecium. Concentration profiles simulating those observed in serum following administration of both low-dose (2 mg/kg) and high-dose (6 mg/kg) daptomycin were bactericidal within 5.5 and 2.8 h, respectively. In contrast, when albumin was added to the growth medium, the corresponding bacterial killing times were slowed to>24 h and 7 h; these results suggest that in the clinical setting, daptomycin dosages of approximately 6 mg/kg are required to achieve bactericidal activity against vancomycin-resistantEnterococcus faecium.     

Comparative analysis of antimicrobial susceptibility among organisms from France, Germany, Italy, Spain and the UK as part of the tigecycline evaluation and surveillance trial.

As part of the tigecycline evaluation and surveillance trial (TEST), bacterial isolates were collected from 39 centres in France, Germany, Italy, Spain and the UK between January 2004 and August 2006. Antimicrobial susceptibilities were determined according to CLSI guidelines. Italy had the highest rate of methicillin-resistant Staphylococcus aureus (36.4%), and was the only country to report vancomycin-resistant Enterococcus faecalis (8.6%). Tigecycline was the only agent to which all Gram-positive isolates were susceptible. For many of the Gram-negative organisms collected, antimicrobial susceptibilities were lowest among isolates from Italy and highest among isolates from Spain. The notable exception was Acinetobacter baumannii, where the poorest susceptibility profile was among isolates from Spain. For A. baumannii, MIC(90)s of imipenem varied from 1 mg/L for isolates in France and Germany to > or =32 mg/L for isolates from Italy and Spain. Tigecycline was the only agent to maintain an MIC(90) of < or =1 mg/L against isolates from all five countries. The in-vitro activity of tigecycline against both Gram-positive and Gram-negative isolates may make it valuable in the treatment of hospital infections, including those caused by otherwise antimicrobial-resistant organisms.     

Investigation of the reformulated Remel Synergy Quad plate for detection of high-level aminoglycoside and vancomycin resistance among enterococci.

We investigated the accuracy of the recently released Remel Synergy Quad plate, a commercially available agar screening method for detecting high-level aminoglycoside and vancomycin resistance among enterococci that is based on the National Committee for Clinical Laboratory Standards recommended guidelines (National Committee for Clinical Laboratory Standards, M7-A3, 1993). The Synergy Quad correctly determined the gentamicin and streptomycin resistance status for > or = 97% of 147 Enterococcus faecalis and Enterococcus faecium isolates tested. Detection of vancomycin resistance also was reliable, as no false susceptibility occurred with 36 vancomycin-resistant E. faecalis and E. faecium strains and false resistance occurred only once with the 47 susceptible strains tested. One strain each of Enterococcus gallinarum and Enterococcus casseliflavus failed to grow on the screen, but because the true nature and significance of resistance in such isolates is unknown the implication of their screen negativity is uncertain. In summary, the Remel Synergy Quad provides a highly accurate and convenient method for susceptibility testing of enterococci against gentamicin, streptomycin, and vancomycin.     

Application of DNA probes for rRNA and vanA genes to investigation of a nosocomial cluster of vancomycin-resistant enterococci.

DNA probes specific for genes encoding rRNA and the glycopeptide resistance gene vanA were used to investigate a cluster of vancomycin-resistant (MICs, > 512 mg/liter) Enterococcus faecalis and Enterococcus faecium isolated from separate patients in a renal unit in a London hospital. When digested with BamHI, 12 of 13 vancomycin-resistant E. faecalis isolates exhibited a common restriction fragment length polymorphism pattern of rRNA genes (ribotype). A vanA probe hybridized with chromosomal DNA in these 12 isolates. The other isolate of vancomycin-resistant E. faecalis had a different ribotype and the vanA gene was located on plasmid DNA. These data suggest that cross-infection with a single strain of vancomycin-resistant E. faecalis occurred in most instances. In contrast, 23 vancomycin-resistant E. faecium isolates showed greater heterogeneity, comprising 8 ribotypes, suggesting that multiple strains were present in the unit. Twenty-one of these 23 isolates harbored a 24-MDa plasmid which hybridized with the vanA probe, implying that interstrain dissemination of a vancomycin resistance plasmid may have occurred among E. faecium isolates in the renal unit.     

Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents,including ceftobiprole,nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006–2010

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n?=?517) exhibited MICs of 2 μg/ml and 0.3 % (n?=?6) demonstrated intermediate susceptibility (MICs of 4 μg/ml). Nearly all isolates (≥99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC₉₀ values were 2 μg/ml for ceftobiprole and 1 μg/ml for nemonoxacin. The MIC₉₀ values of mupirocin and tyrothricin were 0.12 and 4 μg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 μg/ml, the MIC₉₀ values were 2 μg/ml for teicoplanin, 0.5 μg/ml for daptomycin, and 0.5 μg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 μg/ml (2, 0.06, and 0.12 μg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n?=?6), teicoplanin (n?=?1), daptomycin (n?=?2), or tigecycline (n?=?1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 μg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.     

Screening for Staphylococcus aureus with a reduced susceptibility to vancomycin in: a Belgian hospital

The aim of the present study was to investigate the prevalence of vancomycin resistance in clinical methicillin resistant Staphylococcus aureus (MRSA) isolates in our hospital by screening on Mueller-Hinton agar with 5 mg/l teicoplanin (MH-Teico), as recommended by the Comite de l'Antibiogramme of the Societe Francaise de Microbiologie (CA-SFM). Seventeen of 1002 clinical MRSA isolated from 404 patients showed in 2003 growth of at least four colonies on this medium, but only one was confirmed as homogeneous vancomycin-resistant S. aureus (VISA) and five as heterogeneous VISA (hVISA) by population analysis. None of the patients presented with severe infection but awareness is needed and screening on MH-Teico as recommended by CA-SFM is a convenient method. Surveillance should be focused on patients with risk factors for selection of such strains: patients with a prolonged course of glycopeptide therapy and persistence of MRSA infection or colonization.     

Recovery of vancomycin-resistant gram-positive cocci from pediatric liver transplant recipients.

Between November 1988 and October 1989, 49 first-time pediatric liver transplant recipients at the Children's Hospital of Pittsburgh were prospectively monitored for the presence of stool colonization and the development of disease caused by vancomycin-resistant gram-positive cocci (VRGPC). Quantitative stool culturing was done on a weekly basis, and cultures were planted onto a selective medium for VRGPC. Isolates for which the MIC was greater than or equal to 8 were considered resistant to vancomycin. Patients were monitored clinically for the development of infection, and their charts were systematically reviewed for the use of antibiotics. Eighty-six isolates were recovered from 36 of the 49 patients. Enterococcal species were isolated from 31 patients and included Enterococcus gallinarum (n = 28), E. casseliflavus (n = 14), E. faecium (n = 9), E. faecalis (n = 2), E. mundtii (n = 2), and E. durans (n = 1). Stool colonization with vancomycin-resistant enterococci was noted to increase steadily during the first month after transplantation. Only 9 of 31 patients demonstrated clearance of these organisms in serial repeat cultures. Additional isolates of VRGPC included Lactobacillus confusus (n = 13), Lactobacillus spp. (n = 12), and Pediococcus pentosaceus (n = 4). Infection due to VRGPC developed in three patients: a urinary tract infection in two and peritonitis in one. E. faecium was the pathogen in each of these cases. The ranges of MICs of vancomycin were 8 to 32 micrograms/ml for all enterococcal isolates and greater than 128 micrograms/ml for Lactobacillus and Pediococcus isolates. All Lactobacillus and Pediococcus isolates were resistant to teicoplanin, although they were susceptible to daptomycin. All other isolates were susceptible to both teicoplanin and daptomycin. This study demonstrates that stool colonization with VRGPC may be a common and early finding among pediatric liver transplant recipients. However, infection appears to be uncommon.     

High percentage of methicillin-resistant Staphylococcus aureus isolates with reduced susceptibility to glycopeptides in The Netherlands

While testing the in vitro activities of 14 antimicrobial agents against 107 methicillin-susceptible Staphylococcus aureus (MSSA) and 250 methicillin-resistant S. aureus (MRSA) isolates collected in The Netherlands, we found to our surprise that 19 (7.6%) MRSA isolates were suspected of having reduced susceptibilities to the glycopeptides when the Etest system (AB Biodisk, Solna, Sweden) was used with a large inoculum (no. 2 McFarland standard) and an extended incubation time (48 h) on brain heart infusion agar for MIC testing. Eventually, 15 of these isolates were classified as heterogeneously resistant to glycopeptides (heterogeneously glycopeptide-intermediate S. aureus [hGISA] isolates) according to the population analysis profile-area under the curve analysis. The MICs at which 50 and 90% of isolates are inhibited obtained with the Etest system with the large inoculum were as follows: for MSSA isolates, 3.0 and 4.0 micro g/ml, respectively, for both teicoplanin and vancomycin; for MRSA isolates, 3.0 and 8.0 micro g/ml, respectively, for teicoplanin, and 3.0 and 4.0 micro g/ml, respectively, for vancomycin. This is the first report of hGISA isolates in The Netherlands.