Enhancement of Vancomycin Activity by Phenothiazines against Vancomycin‐Resistant Enterococcus Faecium in vitro

Abstract: The antimicrobial and resistance‐reversal activities of seven phenothiazine derivatives were evaluated against vancomycin‐sensitive Enterococcus faecalis ATCC 29212, vancomycin resistant E. faecalis ATCC 51299 and ten vancomycin‐resistant E. faecium strains originating from human infections. Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and vancomycin was investigated using Checkerboard (microbroth dilution) technique. We found that all enterococci strains, regardless of their susceptibility to vancomycin, were inhibited by phenothiazines at concentrations varying from 8 to 256 μg/ml, with thiethylperazine being the most potent inhibitory agent. Besides, all the phenothiazines showed partial synergy with vancomycin and could lessen MIC of vancomycin from 512 to 8 μg/ml at their sub‐inhibitory concentrations. The highest reduction in MIC was observed with chlorpromazine (32 times); however, thiethylperazine and promethazine stood next (24 times). Although resistance modification was observed at concentrations higher than those that phenothiazines reach in vivo, the potential offered by non‐antibiotics justify further animal experiments as well as clinical trials to establish their clinical relevance.     

Screening of Antibacterial Activity of South Brazilian Baccharis. Species

Abstract

South Brazilian Baccharis. species were studied for antibacterial activities against Gram-positive and Gram-negative bacteria using disk diffusion and broth dilution assays. The results showed that the n.-BuOH fraction (100 µg) from Baccharis usterii. Heering exhibited inhibitory activity against Staphylococcus aureus., Enterococcus faecalis., and Enterococcus faecium.. The n.-BuOH fraction of Baccharis spicata. (Lam.) Bailon (1000 µg) was effective against S. aureus., Escherichia coli., Enterococcus faecalis., and Enterococcus faecium.. The crude extract of Baccharis trimera. (Less) A. P. de Candolle (in doses of 1000 µ/disc) showed activity against S. aureus.. The minimum bactericidal concentration (MBC) obtained from n.-BuOH fraction of B. spicata. were 50 mg/ml against S. aureus., E. coli., E. faecalis., and E. faecium.. From the crude extract of B. trimera., a MBC of 25 mg/ml was obtained against S. aureus.. The n.-BuOH fraction of B. usterii. showed a MBC of 25 mg/ml against S. aureus. and 50 mg/ml against E. faecalis. and E. faecium., while the crude extract of this plant showed a MBC of 12.5 mg/ml against S. aureus..     

Alterations in regulatory regions of erm(B) genes from clinical isolates of enterococci resistant to telithromycin

We determined rates of resistance to the ketolide telithromycin in 56 Enterococcus faecalis isolates and 44 Enterococcus faecium isolates collected from hospitals in Korea between 2005 and 2006. Twenty nine (51.8%) isolates of E. faecalis and 35 (79.5%) isolates of E. faecium were resistant to telithromycin (minimum inhibitory concentrations, ≥ 4 μg/mL). All of the telithromycin-resistant E. faecalis carried the erm(B) gene only. Of the telithromycin-resistant E. faecium, 29 resistant strains carried erm(B) only, the other six carried erm(A) and erm(B) together. The nucleotide sequence of the erm(B) regulatory regions from 29 E. faecalis and 29 E. faecium isolates with erm(B) only was analyzed. Five types of alterations were detected. The first and second types had point mutations that destabilize the secondary structure of erm(B) mRNA sequestering the translation initiation region of the structural gene. The third type was identical to erm(Bv1), a previously reported variant of erm(B) with different induction specificity. The fourth and fifth types had point mutations within the critical sequence for induction and a point mutation destabilizing the stem-loop of erm(B) mRNA sequestering the translation initiation region of the structural gene.     

Comparison of Bactericidal Activities of Intermittent and Continuous Infusion Dosing of Vancomycin against Methicillin-Resistant Staphylococcus aureus and Enterococcus faecalis

Study Objective . To describe the pharmacokinetic profiles of vancomycin administered by continuous infusion and intermittent dosing and compare the duration of activity of the regimens. Design . Randomized, open-label, cross-over study. Setting . Clinical research center at an academic medical center. Subjects . Twelve healthy, nonpregnant volunteers age 27.6 ± 2.3 years. Intervention . Subjects received the following intravenous vancomycin regimens: 1 g every 12 hours; 2 g continuous infusion over 24 hours; and 1 g continuous infusion over 24 hours. Dosages were administered with and without gentamicin 2 mg/kg. Measurements and Main Results . Serum samples were collected, drug concentrations determined, and bactericidal activity measured against two isolates each of methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. Subjects had poor tolerability for continuous infusions. Trough concentration for the intermittent regimen was 5.5 ± 1.9 mg/ml, and steady-state concentrations were 8.8 ± 1.6 and 16.9 ± 1.9 mg/ml for 1 and 2 g continuous infusions, respectively. In general, all regimens provided bactericidal activity throughout the study interval. Against one isolate of E. faecalis, 2 g continuous infusion plus gentamicin provided cidal activity for a significantly greater percentage of the dosing interval (p<0.001). Conclusion . Continuous infusion does not greatly improve the activity of vancomycin and should not be routinely administered. However, it may prove useful against isolates with reduced susceptibility to the agent.     

High rates of colonisation by ampicillin-resistant enterococci in residents of long-term care facilities in Porto,Portugal

This study evaluated the occurrence of enterococci resistant to clinically relevant antibiotics in long-term care facility (LTCF) residents in Porto, Portugal, a region with high rates of multidrug-resistant enterococci in infected patients and healthy carriers. Faecal samples from 48 residents in two LTCFs (2015–2016) were enriched (with/without antibiotics) and plated on Slanetz–Bartley with/without the same antibiotics (ampicillin/vancomycin/linezolid). Two colonies per morphology/sample were selected for susceptibility testing and species identification. Clonality was established by PFGE and MLST. Genes coding for vancomycin resistance (vanA/vanB), virulence and plasmids (replicases) were searched by PCR. A total of 285 isolates were obtained, comprising Enterococcus faecalis, Enterococcus faecium, Enterococcus raffinosus and Enterococcus avium colonising 83%, 77%, 27% and 10% of residents, respectively. Residents from both LTCFs were colonised with vancomycin-resistant E. faecium (VanA-VREfm) (4 residents; 8%) and/or ampicillin-resistant (AmpR) (24 residents; 50%) E. raffinosus, E. faecium and E. avium. Enterococcus faecium previously associated with major human clonal lineages (ST18/ST78) or animal clones (ST393) were identified. Some PFGE types of E. faecium, E. raffinosus and E. avium were shared by residents of both LTCFs. Recent antibiotic exposure was significantly associated with colonisation by AmpR enterococci. Residents from Portuguese LTCFs were colonised with high rates of AmpR enterococci and similar rates of VREfm compared with other EU countries. A high colonisation rate with widespread enterococcal lineages that could be selected by antibiotic consumption in LTCFs was uncovered. These findings suggest that antimicrobial stewardship is warranted in LTCFs, which constitutes a significant challenge in a home-based setting.     

Teicoplanin for treating enterococcal infective endocarditis: A retrospective observational study from a referral centre in Spain

This study aimed to evaluate the effectiveness and safety of teicoplanin for treating enterococcal infective endocarditis (EIE). A retrospective analysis of a prospective cohort of definite EIE patients treated with teicoplanin in a Spanish referral centre (2000–2017) was performed. The primary outcome was mortality during treatment. Secondary outcomes were mortality during 3-month follow-up, adverse effects and relapse. A total of 22 patients received teicoplanin, 9 (40.9%) as first-line (8 Enterococcus faecium and 1 Enterococcus faecalis) and 13 (59.1%) as salvage therapy (13 E. faecalis). Median (IQR) age was 71.5 (58.3–78) years and Charlson comorbidity index was 4.5 (3–7). Five (22.7%) affected prosthetic valves. Median duration of treatment in survivors was 53 (42.5–61) days for antibiotics and 27 (17–41.5) days for teicoplanin [median dose 10 (10–10.8) mg/kg/day]. Reasons for teicoplanin use were resistance to β-lactams (40.9%), adverse events with previous regimens (31.8%) and outpatient parenteral antimicrobial therapy (OPAT) (27.3%). Teicoplanin was withdrawn due to adverse events in 2 patients (9.1%). Five patients (22.7%) died during treatment: four in the first-line (three with surgery indicated but not performed) and one in the salvage therapy group (surgery indicated but not performed). Two deaths (11.8%) occurred over the 3-month follow-up. There were no relapses during a median of 43.2 (22.1–69.1) months. Teicoplanin can be used as an alternative treatment for susceptible E. faecium IE and as a salvage therapy in selected patients with E. faecalis IE when adverse events develop with standard regimens or to allow OPAT.     

Design, synthesis, and biological evaluation of β-lactam antibiotic-based imidazolium- and pyridinium-type ionic liquids

We herein report the preparation and investigation of antibacterial activity of biocidal ionic liquids (ILs) consisting of cationic imidazolium or pyridinium and an anionic β‐lactam antibiotic. The antibacterial properties were quantified by measuring the minimum inhibitory concentration and minimum bactericidal concentration against Escherichia coli O157:H7, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecium. In general, the ILs had improved antibacterial activity than their parent materials, whether individually or in combination. In 83% of the experiments, the ampicillin ILs (Amp‐ILs) had better antibacterial activities than their quaternary halide parent materials, whereas in 92% of the experiments, Amp‐ILs outperformed the commercially available sodium ampicillin salt. Amp‐ILs had up to 43 times improved antibacterial activity than sodium ampicillin. Overall, when normalized for ampicillin content, ILs had greater antimicrobial activity against E. coli O157:H7, K. pneumoniae, S. aureus, and E. faecium than sodium ampicillin alone.     

Synergistic activity of vancomycin and teicoplanin alone and in combination with streptomycin against Enterococcus faecalis strains with various vancomycin susceptibilities

The synergy between two glycopeptides, vancomycin (Vm) and teicoplanin (Tec) and streptomycin (Sm) was studied by time-kill method. Five clinical vanB resistant Enterococcus faecalis (ENC) isolates with variable Vm-susceptibility were used. Different concentrations of Vm, Tec and Sm representing therapeutic concentrations were combined. Antibacterial activity was related to the concentrations of Vm and Sm, and Vm susceptibility to ENC. For strains with Vm MIC up to 64 mg/l, synergy was achieved with higher concentrations of Vm and Sm, while all combinations of Tec and Sm were synergistic against all strains except ENC 29. For ENC 29 with Vm MIC of 512 mg/l and Tec MIC of <1 mg/l, none of the combinations was synergistic. The significance of these in vitro results needs further investigation in vivo.     

Daptomycin for the treatment of enterococcal bacteraemia: results from the Cubicin Outcomes Registry and Experience (CORE)

Enterococcal infections are a common cause of nosocomial bloodstream infections. Vancomycin resistance and the emergence of linezolid resistance necessitate alternative therapies. Studies in vitro as well as animal and case studies suggest that daptomycin may be effective in enterococcal infections. Patients with positive blood cultures for enterococci in the Cubicin^® Outcomes Registry and Experience (CORE) 2005–2006 were identified. Patients with endocarditis, intracardiac foreign body infections or non-speciated enterococci were excluded. Outcome was assessed using protocol-defined criteria. Of 159 patients included in the efficacy population, Enterococcus faecium and Enterococcus faecalis were isolated in 120 (75.5%) and 39 (24.5%) patients, respectively. Vancomycin resistance was detected in 91% and 23% of patients with E. faecium and E. faecalis infections, respectively. Prior to daptomycin, 94/159 (59.1%) and 35/159 (22.0%) patients had received vancomycin and linezolid, respectively. Daptomycin was first-line therapy in 27/159 cases (17%). Success was observed in 139/159 patients (87%) and in 104/120 (87%) and 35/39 (90%) patients with E. faecium and E. faecalis infections, respectively. Among the safety population (n = 211), 20 (9.5%) experienced 28 adverse events possibly related to daptomycin, 8 of which were considered serious. Daptomycin may be a useful agent for treating enterococcal bacteraemia caused by E. faecium or E. faecalis. Further studies are warranted.     

In vitro prevention of the emergence of daptomycin resistance in Staphylococcus aureus and enterococci following combination with amoxicillin/clavulanic acid or ampicillin

Daptomycin is bactericidal against meticillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate-resistant S. aureus (GISA) and vancomycin-susceptible and -resistant enterococci. However, selection for daptomycin-resistant derivatives has occasionally been reported during therapy in humans. Here we evaluate whether selection for daptomycin-resistant S. aureus or enterococci could be prevented in vitro by combining daptomycin with amoxicillin/clavulanic acid, ampicillin, gentamicin or rifampicin. Six strains of S. aureus (four MRSA and two GISA) and four strains of enterococci (two Enterococcus faecalis and two Enterococcus faecium) were serially exposed in broth to two-fold stepwise increasing concentrations of daptomycin alone or in combination with a fixed concentration [0.25× minimum inhibitory concentration (MIC)] of either of the second agents. The daptomycin MIC was examined after each cycle. Exposure to daptomycin alone gradually selected for S. aureus and enterococci with an increased MIC. Gentamicin did not prevent the emergence of daptomycin-resistant bacteria. Rifampicin was also unable to prevent daptomycin resistance, although resistance was slightly delayed. In contrast, amoxicillin/clavulanic acid or ampicillin prevented or greatly delayed the selection of daptomycin-resistant mutants in S. aureus and enterococci, respectively. Addition of amoxicillin/clavulanic acid or ampicillin to daptomycin prevents, or greatly delays, daptomycin resistance in vitro. Future studies in animal models are needed to predict the utility of these combinations in humans.     

2017年福州市第二医院病原菌的分布及耐药性分析

目的 了解2017年福州市第二医院临床分离病原菌的分布及对抗菌药物的敏感性,为临床用药提供指导。方法 共收集2 720株非重复分离菌,采用纸片扩散法或自动化仪器法进行药敏试验,按CLSI标准判读药敏结果。结果 2 720株细菌中,标本主要来源于伤口分泌物（989株）,占36.3%。革兰阴性菌1 786株,占65.7%,主要为大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、鲍曼不动杆菌、嗜麦芽窄食单胞菌和阴沟肠杆菌;革兰阳性菌934株,占34.3%,主要为金黄色葡萄球菌、粪肠球菌和凝固酶阴性葡萄球菌。耐甲氧西林耐药株金黄色葡萄球菌、凝固酶阴性葡萄球菌的检出率分别为42.7%、84.2%。未发现对万古霉素、替考拉宁和利奈唑胺耐药的葡萄球菌。粪肠球菌对大多数抗菌药物的耐药率明显低于屎肠球菌。肠球菌属中未发现万古霉素、利奈唑胺、替考拉宁耐药的肠球菌。除对黏菌素100%敏感外,铜绿假单胞菌对其他常见抗菌药物的耐药率均较低,鲍曼不动杆菌除对黏菌素敏感外,对其他药物的耐药性均较高,均达46.2%以上。结论 2017年福州市第二医院病原菌耐药形势依旧严峻,应加强合理用药,避免交叉感染。     

Synergistic and bactericidal activities of mecillinam,amoxicillin and clavulanic acid combinations against extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in 24-h time–kill experiments

This study aimed to evaluate the potential synergistic and bactericidal effects of mecillinam in combination with amoxicillin and clavulanic acid against extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Eight clinical E. coli isolates with varying susceptibility to mecillinam [minimum inhibitory concentrations (MICs) of 0.125 mg/L to >256 mg/L] and high-level resistance to amoxicillin (MICs > 256 mg/L) were used. Whole-genome sequencing was performed to determine the presence of β-lactamase genes and mutations in the cysB gene. The activities of single drugs and the combinations of two or three drugs were tested in 24-h time–kill experiments. Population analysis was performed for two strains before and after experiments. Only one strain had a mutation in the cysB gene resulting in an amino acid substitution. With the two-drug combinations, initial killing was observed both with mecillinam and amoxicillin when combined with clavulanic acid. Synergy was observed with mecillinam and clavulanic acid against one strain and with amoxicillin and clavulanic acid against three strains. However, following significant re-growth, a bactericidal effect was found only with amoxicillin and clavulanic acid against two strains. Pre-existing subpopulations with elevated mecillinam MICs were detected before experiments and were selected with mecillinam alone or in two-drug combinations. In contrast, the three-drug combination showed enhanced activity with synergy against six strains, a bactericidal effect against all eight strains, and suppression of resistance during 24-h antibiotic exposure. This combination may be of clinical interest in the treatment of urinary tract infections caused by ESBL-producing E. coli.     

Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G

Combination of antibiotics with natural products is a promising strategy for potentiating antibiotic activity and overcoming antibiotic resistance. The purpose of the present study was to investigate whether morusin and kuwanon G, prenylated phenolics in Morus species, have the ability to enhance antibiotic activity and reverse antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis. Commonly used antibiotics (oxacillin, erythromycin, gentamicin, ciprofloxacin, tetracycline, clindamycin) were selected for the combination studies. Checkerboard and time-kill assays were used to investigate potential bacteriostatic and bactericidal synergistic interactions, respectively between morusin or kuwanon G and antibiotics. According to both fractional inhibitory concentration index and response surface models, twenty combinations (14 morusin-antibiotic combinations, six kuwanon G-antibiotic combinations) displaying bacteriostatic synergy were identified, with 4–512-fold reduction in the minimum inhibitory concentration values of antibiotics in combination. Both morusin and kuwanon G reversed oxacillin resistance of methicillin-resistant Staphylococcus aureus. In addition, morusin reversed tetracycline resistance of Staphylococcus epidermidis. At half of the minimum inhibitory concentrations, combinations of morusin with oxacillin or gentamicin showed bactericidal synergy against methicillin-resistant Staphylococcus aureus. Fluorescence and differential interference contrast microscopy and scanning electron microscopy showed an increase in the membrane permeability and massive leakage of cellular content in methicillin-resistant Staphylococcus aureus exposed to morusin or kuwanon G. Overall, our findings strongly indicate that both prenylated compounds are good candidates for the development of novel antibacterial combination therapies.     

Characteristics of clinical and environmental vanM-carrying vancomycin-resistant enterococci isolates from an infected patient

vanM, an uncommon glycopeptide resistance gene, was first identified in an Enterococcus faecium isolate (Efm-HS0661) from Shanghai, China, in 2006 and has been predominant in this city since 2011. A vanM-carrying E. faecium was isolated from the bloodstream of a patient in an intensive care unit (ICU) in Hangzhou, China, in 2014. Further surveillance screening of a rectal swab and environmental surfaces of the patient yielded a large number of vanM-positive E. faecium. These isolates (including 1 from the bloodstream, 1 from the rectal swab and 43 representative isolates from environmental samples) were classified into four pulsed-field gel electrophoresis (PFGE) patterns and two sequence types (ST78 and ST564). PCR amplification and sequence analysis indicated that the genetic structure surrounding the vanM gene of these isolates was similar to that of the original vanM-carrying isolate Efm-HS0661. This study highlights the emergence of infections and environmental contamination caused by vanM-carrying E. faecium in an ICU of another Chinese city outside of Shanghai.     

High-level ciprofloxacin resistance among hospital-adapted Enterococcus faecium (CC17)

Hospital-adapted Enterococcus faecium differ from their colonising variants in humans and animals by additional genomic content. Molecular typing based on multilocus sequence typing (MLST) allows allocation of isolates to specific clonal complexes (CCs), such as CC17 for hospital-adapted strains. Acquired ampicillin resistance is a specific feature of these hospital isolates, especially in Europe. A few recent reports have described acquired high-level ciprofloxacin resistance as a supposed feature of hospital-adapted E. faecium strains. In the present retrospective analysis, ciprofloxacin minimum inhibitory concentrations (MICs) of 609 clinical isolates from German hospital patients (1997–2007) were determined and a breakpoint for high-level resistance was deduced (>16 mg/L). Acquired high-level ciprofloxacin resistance was distributed among isolates of 26 different MLST types (all CC17), indicating a wide prevalence of this acquired resistance trait among the hospital-adapted E. faecium population. High-level ciprofloxacin resistance was linked to gyrA and parC mutations in 98 investigated isolates. Eleven different allele types or combinations thereof were identified. Their allocation to specific MLST and pulsed-field gel electrophoresis (PFGE) types revealed differences in the emergence and spread of corresponding mutations and strains.     

Non-susceptibility to tigecycline in enterococci from hospitalised patients, food products and community sources

In this study, the in vitro activity of tigecycline against 1140 enterococci collected from humans, food products, animals and the environment in Portugal (1996-2008) was analysed. Ten isolates (seven Enterococcus faecalis and three Enterococcus spp.) non-susceptible to tigecycline (minimum inhibitory concentrations of 0.5-1.0 mg/L), which were also resistant to tetracycline and minocycline, were mostly observed in samples collected before the introduction of tigecycline in the therapeutic arsenal. The E. faecalis isolates were recovered from hospitalised patients (n = 2; ST319/CC2 and ST34), healthy humans (n = 2; ST21/CC21), chicken meat (n = 1; ST260) as well as from two swine samples. The remaining isolates were also recovered from chicken meat (n = 1; Enterococcus gallinarum) and swine (n = 2; Enterococcus hirae and Enterococcus spp.). Recovery of enterococcal isolates with reduced susceptibility to tigecycline amongst different reservoirs, including animals for food consumption, suggests that selection of tigecycline-resistant isolates by antibiotics other than tigecycline might occur in non-clinical settings.     

A novel structure of Tn4001-truncated element, type V, in clinical enterococcal isolates and multiplex PCR for detecting aminoglycoside resistance genes

A multiplex polymerase chain reaction (PCR) was established for detecting aacA-aphD, aph(2')-Ib, aph(2')-Ic and aph(2')-Id, encoding high-level gentamicin resistance (HLGR), and aadA and aadE, encoding high-level streptomycin resistance (HLSR), in enterococci. The assay was implemented for 419 enterococcal blood and urine isolates recovered from patients at a university hospital in Thailand. Among the isolates tested, 56.1% (235 isolates) and 58.9% (247 isolates) contained aacA-aphD and aadE, respectively. The aph(2')-Ib, aph(2')-Ic, aph(2')-Id and aadA genes were not found in any isolate. Among the isolates carrying the aacA-aphD gene, 99.1% exhibited a HLGR phenotype. All 235 enterococcal isolates containing aacA-aphD were further studied by PCR to characterise the structure of the resistance determinants carrying the aacA-aphD gene. The result revealed that only 22.6% carried Tn4001-related element, whereas the remaining isolates contained Tn4001-truncated element. No Tn4001-IS257 hybrid structure was detected. The majority of isolates carrying Tn4001-related element were Enterococcus faecalis (77.4%). Among Tn4001-truncated elements detected, all previously reported types (types I-IV) were found. Furthermore, a novel Tn4001-truncated type, designated type V, was also identified.     

Effect of Human Serum on Killing Activity of Vancomycin and Teicoplanin against Staphylococcus aureus

Study Objective . To investigate the effects of pooled human serum (PHS) on the killing activity of vancomycin and teicoplanin against two isolates of Staphylococcus aureus from patients treated for endocarditis. Design . An in vitro assessment of antibiotic susceptibility and killing rates. Setting . An urban university teaching hospital. Patients . Pooled human serum from patients treated for endocarditis. Interventions . Two clinical isolates of Staphylococcus aureus were obtained from patients treated for endocarditis. Media consisted of cation-supplemented Mueller-Hinton broth alone and in 1:1 dilutions with PHS, 2-hour heat-inactivated PHS (HI-PHS), ultrafiltrate (UF), and 2-hour heat-inactivated ultrafiltrate (HI-UF). Heat inactivation of PHS and UF was accomplished by treatment at 56°C for 2 hours. Measurements and Main Results . Killing curves with vancomycin and teicoplanin were performed using drug concentrations of 45 μg/ml and a starting inoculum of ∼1 × 10⁶ colony-forming units (cfu)/ml. Bactericidal rates (-log cfu/ml/hr) were calculated from the slope of the killing curves over 0–12 hours (mean 3–8 replicates). Conclusions . The killing activity of vancomycin in PHS and HI-PHS against both isolates was significantly greater than all other media tested (p<0.0001). Ultrafiltrate tended to reverse this enhancement effect. Addition of PHS or UF did not enhance teicoplanin's killing activity against either isolate. Further investigations in our laboratory will determine if the factor is antibiotic class or organism specific.     

2015—2019年天津医科大学肿瘤医院恶性肿瘤患者血流感染病原菌分布及耐药性分析

目的 探讨天津医科大学肿瘤医院恶性肿瘤患者血流感染病原菌分布及耐药情况,为临床合理用药提供理论依据。方法 对2015—2019年天津医科大学肿瘤医院血培养结果进行回顾性分析。结果 2015年1月—2019年12月天津医科大学肿瘤医院经血培养分离出菌株1 471株,在科室分布方面,肝胆胰腺肿瘤科、胃肠肿瘤科、血液肿瘤科占比均超过10%;在病原菌分布方面,革兰阴性菌占67.7%;革兰阳性菌占28.1%;真菌占4.1%。革兰阴性菌以大肠埃希菌、肺炎克雷伯菌、阴沟肠杆菌为主;革兰阳性菌中,以金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、屎肠球菌为主;在耐药性方面,碳青霉烯类、哌拉西林他唑巴坦、氟喹诺酮类、阿米卡星对主要肠杆菌科细菌保持良好的敏感性。葡萄球菌属中,表皮葡萄球菌中甲氧西林耐药菌株检出率高于金黄色葡萄球菌,表皮葡萄球菌整体耐药率高于金黄色葡萄球菌。肠球菌属中,屎肠球菌的整体耐药率高于粪肠球菌。结论 天津医科大学肿瘤医院肿瘤患者血流感染的病原菌以革兰阴性菌为主,与其他肿瘤医院报道一致。耐药率低于2019年CHINET三甲医院细菌耐药监测数据。