Antimicrobial activity of tigecycline (GAR-936) against Enterococcus faecium and Staphylococcus aureus used alone and in combination

STUDY OBJECTIVE: To evaluate the antimicrobial properties of tigecycline, both alone and in combination with other antibiotics, against multidrug-resistant strains of Enterococcus faecium and Staphylococcus aureus. DESIGN: In vitro study. SETTING: University laboratory. MEASUREMENTS AND MAIN RESULTS: Tigecycline, both alone and in combination with other antimicrobial agents, was evaluated against two strains of vancomycin-resistant E. faecium (VREF), three glycopeptide-intermediately resistant S. aureus strains, and one methicillin-resistant S. aureus strain. Tigecycline's activity was compared with that of vancomycin, gentamicin, rifampin, and doxycycline, using time-kill studies and analysis of minimum inhibitory concentrations and minimum bactericidal concentrations. Tigecycline also was evaluated in combination with vancomycin, gentamicin, rifampin, and doxycycline in time-kill studies. The number of log10 colony-forming units/ml at 24 hours was compared among treatment groups and growth control by analysis of variance. All isolates were susceptible to tigecycline, regardless of their susceptibilities to vancomycin or doxycycline. In time-kill studies, tigecycline significantly inhibited the bacterial inoculum of all isolates (p < 0.05). Although none of the tigecycline combinations studied had enhanced killing activity against VREF, when gentamicin was combined with tigecycline, improved effects were found against both strains. Against three of the S. aureus strains tested, the combination of gentamicin and tigecycline demonstrated enhanced or improved activity independently of each strain's susceptibility to gentamicin. CONCLUSION: The multidrug-resistant, gram-positive bacteria tested, including doxycycline-resistant isolates, were susceptible to tigecycline. The combination of tigecycline and gentamicin may have improved or enhanced activity against strains of vancomycin-resistant enterococci and S. aureus.     

In vitro synergism of two-drug combinations among cefamandole, flomoxef and imipenem against MRSA

First of all, vancomycin (VCM) showed good antimicrobial activity against Staphylococcus aureus including methicillin-sensitive and -resistant strains. MIC90 of VCM was 1.56 micrograms/ml. Effects of different 2-drug combinations among cefamandole (CMD), flomoxef (FMOX) and imipenem (IPM), and activity of VCM alone were examined in vitro against 5 clinical isolates of methicillin-sensitive S. aureus (MSSA) and 22 isolates of methicillin-resistant S. aureus (MRSA). In a checkerboard study, synergism was observed against 4 strains of the 5 MSSA and all 22 strains of the MRSA with IPM and CMD, FMOX and IPM, and FMOX and CMD combinations. Mean MICs of these combinations were as low as one-fourth to one-tenth as those of individual drugs.     

利奈唑胺、替考拉宁和万古霉素等抗菌药物对常见需氧革兰阳性球菌的体外抗菌活性

目的评价利奈唑胺、替考拉宁和万古霉素等抗菌药物的体外抗菌活性。方法采用琼脂稀释法对临床收集的132株革兰阳性球菌进行抗菌活性测定,记录其各自的MIC并进行比较。结果利奈唑胺、替考拉宁及万古霉素3药对革兰阳性球菌均有较大抗菌活性,敏感率均为100%,包括其中的耐甲氧西林葡萄球菌和青霉素中介肺炎链球菌均有良好抗菌作用。3药在部分革兰阳性球菌的抗菌作用中与利福平相仿,但比氨基糖苷类抗生素和氟喹诺酮类抗菌药强。在对甲氧西林敏感金葡萄的抗菌活性中,替考拉宁的MIC90均为利奈唑胺和万古霉素的4倍;在对甲氧西林敏感凝固酶阴性葡萄球菌的抗菌活性中,替考拉宁的MIC90分别均为利奈唑胺和万古霉素的8倍;而在青霉素敏感和中介肺炎链球菌的抗菌活性中,替考拉宁的MIC90为利奈唑胺的1/16,为万古霉素的1/8;在肠球菌属的抗菌活性中,万古霉素的MIC90分别为利奈唑胺的2倍,是替考拉宁的4倍和8倍。结论利奈唑胺、替考拉宁以及万古霉素等三药对革兰阳性球菌有较大的抗菌作用,对部分革兰阳性菌的抗菌作用与利福平相仿,但比其他如氨基糖苷类抗生素和氟诺酮类抗菌药更优,是临床革兰阳性球菌严重感染的有效药物。     

Antimicrobial susceptibility of Gram-positive bacterial isolates from the Asia-Pacific region and an in vitro evaluation of the bactericidal activity of daptomycin, vancomycin, and teicoplanin: a SENTRY Program Report (2003-2004)

Medical centres in eight countries in the Asia-Pacific region provided 2391 isolates for the SENTRY Antimicrobial Surveillance Program during 2003-2004 to determine their susceptibility to several antimicrobial classes, including daptomycin. Daptomycin, vancomycin and teicoplanin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined for 120 isolates of Staphylococcus aureus, which included wild-type (WT) methicillin-resistant S. aureus (MRSA) and strains with decreased susceptibility to vancomycin (hetero-vancomycin-intermediate S. aureus (hVISA)). Oxacillin-resistant staphylococcal isolates were much less susceptible to the other tested agents compared with oxacillin-susceptible strains. Vancomycin resistance was higher among Enterococcus faecium (10.3%) than Enterococcus faecalis (0.4%), and macrolide resistance was high both for beta-haemolytic (17.7%) and viridans group (48.7%) streptococci. Daptomycin (MIC for 90% of the organisms (MIC(90))=0.5-1mg/L) was two-fold more potent than vancomycin, with >99% susceptibility when tested against staphylococci. All tested isolates of E. faecalis (MIC(90)=2mg/L) and beta-haemolytic streptococci (MIC(90)=0.5mg/L) were susceptible to daptomycin. Daptomycin MIC and MBC values were slightly higher for the hVISA isolates compared with WT-MRSA, with MBC/MIC ratios of only 1-2 for both groups. The MBC/MIC ratio for vancomycin was often greater when tested against these strains, particularly hVISA. In contrast, teicoplanin MBC/MIC ratios were significantly higher, with many of the strains showing values consistent with tolerance (>or=32). Daptomycin was demonstrated to have excellent in vitro activity when tested against Gram-positive isolates collected from Asia-Pacific countries, including hVISA strains.     

The in vitro activity of ramoplanin (A-16686/MDL 62,198), vancomycin and teicoplanin against methicillin-susceptible and methicillin-resistant Staphylococcus spp

Ramoplanin (A-16686/MDL 62,198) is a novel lipoglycopeptide antimicrobial, comprised of three closely related polypeptides containing chlorinated phenyl moieties and D-mannose, isolated from the fermentation products of Actinoplanes sp. ATCC 33076. The antimicrobial activity of ramoplanin is limited to Gram-positive bacteria and its reportedly unacceptable administration side-effects suggest that any potential clinical role will be limited to the topical therapy of superficial skin infections and the eradication of bacteria, representing a possible nosocomial cross-infection source, from carriage sites. In this study the MICs of ramoplanin have been determined for methicillin-susceptible and methicillin-resistant isolates of Staphylococcus aureus, S. epidermidis and S. haemolyticus and compared with those of two glycopeptide antimicrobials, vancomycin and teicoplanin. MICs were determined using an agar incorporation technique in Mueller-Hinton medium with an inoculum of 10(5) cfu. Ramoplanin was 2-8 times more active than either vancomycin or teicoplanin against methicillin-susceptible and methicillin-resistant isolates of S. aureus and methicillin-susceptible isolates of S. epidermidis. Isolates of methicillin-resistant S. epidermidis and both methicillin-susceptible and -resistant isolates of S. haemolyticus were generally less susceptible to teicoplanin than to vancomycin. Ramoplanin was significantly more active than either vancomycin or teicoplanin against these isolates. These results suggest that the clinical evaluation of ramoplanin as a topical antibacterial agent for the control of superficial infections caused by Staphylococcus spp. and for the eradication of methicillin-resistant S. aureus from carriage sites, is justified.     

In vitro combined bactericidal activity of cefpirome and glycopeptides against glycopeptides and oxacillin-resistant staphylococci

Infections caused by coagulase-negative staphylococci are becoming increasingly important, particularly those of nosocomial origin, as the organisms are frequently multi-resistant. New antimicrobial strategies are needed. The bactericidal activity of a combination of cefpirome with either vancomycin or teicoplanin against 12 strains of methicillin-resistant staphylococci with a decreased susceptibility to teicoplanin was determined in vitro by a time killing method. Strains Mu3 and Mu50 of Staphylococcus aureus were also studied. Cefpirome (0.125-0.5 x MIC) combined with vancomycin (0.25-1 x MIC) or teicoplanin (0.125-1 x MIC) acted synergically against 12 isolates over 18 h in most cases. A synergistic killing effect was also observed with the Mu3 and Mu50 strains of glycopeptide-intermediate S. aureus but over a longer period.     

Detection of an integrated tetracycline-resistance plasmid in Staphylococcus aureus from a Nigerian hospital

The genetics of tetracycline-resistance determinants was studied in eight methicillin-resistant and two methicillin-sensitive Staphylococcus aureus isolated from a Nigerian hospital. Curing and transfer experiments demonstrated that one methicillin-sensitive S. aureus isolate WBG4762, had a 4.4 kb extrachromosomal plasmid- as well as a chromosomally-mediated tetracycline resistance. All others had chromosomal tetracycline resistance and were resistant to either tetracycline and minocycline or tetracycline only. The two methicillin-susceptible isolates were resistant to both tetracycline and minocycline. Chromosomal DNA from all the resistant isolates hybridized with a digoxigenin-11-dUTP labeled 4.4 kb tetracycline-resistance plasmid probe indicating that they contained tetracycline-resistance plasmids similar to the probe integrated into their chromosomes. The results demonstrated the presence of integrated tetracycline-resistance plasmid in both methicillin-resistant and methicillin-susceptible S. aureus resistant to tetracycline and minocycline as well as those resistant only to tetracycline. This is the first demonstration of an integrated tetracycline-resistance plasmid in methicillin-sensitive S. aureus and suggests that the integrated tetracycline-resistance plasmid may be widespread in S. aureus.     

Activities of antimicrobial agents against 8,474 clinical isolates obtained from 37 medical institutions during 2000 in Japan

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.     

In vitro antimicrobial activity of nanoconjugated vancomycin against drug resistant Staphylococcus aureus

The mounting problem of antibiotic resistance of Staphylococcus aureus has prompted renewed efforts toward the discovery of novel antimicrobial agents. The present study was aimed to evaluate the in vitro antimicrobial activity of nanoconjugated vancomycin against vancomycin sensitive and resistant S. aureus strains. Folic acid tagged chitosan nanoparticles are used as Trojan horse to deliver vancomycin into bacterial cells. In vitro antimicrobial activity of nanoconjugated vancomycin against VSSA and VRSA strains was determined by minimum inhibitory concentration, minimum bactericidal concentration, tolerance and disc agar diffusion test. Cell viability and biofilm formation was assessed as indicators of pathogenicity. To establish the possible antimicrobial mechanism of nanoconjugated vancomycin, the cell wall thickness was studied by TEM study. The result of the present study reveals that nano-sized vehicles enhance the transport of vancomycin across epithelial surfaces, and exhibits its efficient drug-action which has been understood from studies of MIC, MBC, DAD of chitosan derivative nanoparticle loaded with vancomycin. Tolerance values distinctly showed that vancomycin loaded into nano-conjugate is very effective and has strong bactericidal effect on VRSA. These findings strongly enhanced our understanding of the molecular mechanism of nanoconjugated vancomycin and provide additional rationale for application of antimicrobial therapeutic approaches for treatment of staphylococcal pathogenesis.     

Melaleuca alternifolia essential oil possesses potent anti-staphylococcal activity extended to strains resistant to antibiotics

Melaleuca alternifolia Cheel essential oil (TTO) and its major component terpinen-4-ol were examined against a large number of clinical isolates of Staphylococcus aureus to establish their anti-staphylococcal activities. Classic and established procedures were used to study M.I.C., time-kill curves, synergism and mutational frequency. The anti-staphylococcal activity of terpinen-4-ol and TTO were superior to those of antibiotics belonging to the major families (all the tested drugs are for topical use or included in ointments, eye drops or used during surgery); terpinen 4-ol and TTO were active against strains resistant to mupirocin, fusidic acid, vancomycin, methicillin and linezolid. TTO and terpinen-4-ol were bactericidal as revealed by time-kill curves; the frequency of mutational frequency to TTO was < 2.9 x 10 9. The study demonstrates good anti-staphylococcal activity of TTO and terpinen-4-ol against a large number of S.aureus isolates and suggests the possible application of these agents for topical treatment of staphylococcal infections. This is the first extensive study on the anti-staphylococcal activity of TTO. The results suggest that this compound may have application as a topical agent for the control of superficial staphylococcal infections, including activity against organisms resistant to antibiotics which can be used, or are specific, for topical use.     

Comparison of vancomycin pharmacodynamics (1 g every 12 or 24 h) against methicillin-resistant staphylococci

This study compared the duration of serum bactericidal activity for vancomycin, 1 g every 12 or 24 h at steady state, against methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CNS). All four test isolates were susceptible to vancomycin with minimal inhibitory concentration (MIC) values of either 2 or 4 mg/l. Serum bactericidal titres (SBTs) were run in duplicate and serum bactericidal activity (SBA) was defined as the time points at which all subject SBTs were greater than or equal to 1:2. For the every 12-h regimen, SBA was 10-12 h. With the every 24-h regimen, the duration of SBA was 10-16 h for MRSA and 8-10 h for MR-CNS. The pharmacodynamic data suggest that for those with good renal function a Q12h dosing interval is most appropriate for MR-CNS or staphylococcal isolates with MICs of 4.     

Response of complicated methicillin-resistant Staphylococcus aureus endocarditis to the addition of trovafloxacin

The newer fluoroquinolones have many properties such as safety, bioavailability, and tissue penetration that make them attractive in the therapy of complicated infections. Unfortunately, the rapid development of resistance by Staphylococcus aureus to ciprofloxacin has dampened interest in these agents for serious staphylococcal infections. A patient with right-sided methicillin-resistant Staphylococcus aureus (MRSA) endocarditis with a complicated clinical course received trovafloxacin in addition to vancomycin and rifampin. He was initially treated with vancomycin, gentamicin, and rifampin for serious MRSA infection, but because of complications, including septic central nervous system emboli, persistent fever, and leukocytosis, gentamicin was stopped and trovafloxacin begun. After this addition the patient improved and completely recovered. In vitro and animal model data show that many newer fluoroquinolones have excellent activity against S. aureus, including MRSA, and are also less likely to induce resistance. Animal models of endocarditis support their efficacy in serious staphylococcal infections.     

In vitro antibacterial activity of FK482, a new orally active cephalosporin

FK482 is a new orally active cephem antibiotic which offers some advantages over the commercially available oral beta-lactam antibiotics. It displayed a broad spectrum of activity in vitro against stock strains of Gram-positive and Gram-negative aerobes and anaerobes. FK482 was more active in vitro than cefixime (CFIX), cefaclor (CCL) or cephalexin (CEX) against clinical isolates of Gram-positive organisms such as methicillin-sensitive Staphylococcus aureus, coagulase-negative Staphylococci including Staphylococcus epidermidis and strains of the Streptococcus group. Moderate activity was found against methicillin-resistant S. aureus and Enterococcus faecalis. Against clinical isolates of many Gram-negative species, including opportunistic pathogens, FK482 had good in vitro activity similar or slightly inferior to that of CFIX but superior to that of CCL or CEX. However, it was clearly inferior to CFIX in activity against Serratia marcescens, and was inactive against Pseudomonas aeruginosa. Strains of S. aureus resistant to methicillin were moderately susceptible to FK482. All tested strains of Klebsiella pneumoniae resistant to CCL and CEX were susceptible to FK482, as were all the strains of Escherichia coli, Proteus mirabilis, Haemophilus influenzae and Branhamella catarrhalis resistant to amoxicillin (AMPC). FK482, like CFIX, was relatively stable to all type of beta-lactamases except Bacteroides fragilis and its stability was superior to that of CCL or CEX. The antibacterial activity of FK482 against CSH2 strains containing ampicillin-resistance plasmids was not affected by the presence of the ampicillin resistance determinants. FK482 showed higher affinity for the penicillin-binding proteins (PBPs) (3, 2 and 1) of S. aureus than did CFIX, CCL and CEX. FK482 also showed very high affinity for the PBPs (2 and 3) of E. faecalis and PBPs (3, 1a, 4, 2 and 1 bs) of E. coli. The bactericidal activity of FK482 against S. aureus was almost as strong as that of AMPC and superior to that of CCL or CEX. Against Gram-negative bacteria such as E. coli, K. pneumoniae and P. mirabilis, FK482 was similar to CFIX and superior to CCL and CEX in bactericidal activity.     

Comparative in vitro activity of CI934, a new fluoroquinolone, alone and in combination with coumermycin, against gram-positive bacteria

The in vitro activity of Cl934, a new quinolone antimicrobial agent, was studied against 314 strains of Gram-positive bacteria representing 6 genera: Staphylococcus aureus, Streptococcus faecalis, S. agalactiae, S. pyogenes, S. pneumoniae, S. milleri, viridans streptococci, Listeria monocytogenes, Corynebacterium JK, Mycobacterium fortuitum and Bacillus spp.; and compared with that of enoxacin, ciprofloxacin, penicillin G, ampicillin, coumermycin, oxacillin, vancomycin, teicoplanin, rifampin, rifapentine, LM 427, erythromycin, minocycline, tetracycline and clindamycin. The agar dilution method was used. Cl934 was very active in vitro, with MIC90 less than or equal to 0.5 mg/l against most species tested, except for S. faecalis and M. fortuitum. It was usually 2 to 8-fold more active than ciprofloxacin. Cl934 was also tested by the killing curve method, alone and in combination with coumermycin. It was rapidly bactericidal against most species tested, including S. faecalis. A synergistic interaction was observed with coumermycin against S. aureus, S. agalactiae, S. milleri and S. faecalis. The only antagonistic interaction occurred against L. monocytogenes exposed to 8 X MIC of Cl934 with 2 X MIC of coumermycin.     

Antimicrobial activity of fosfomycin against beta-lactamase-producing methicillin-sensitive Staphylococcus aureus and methicillin-sensitive coagulase-negative staphylococci

Antimicrobial activity of fosfomycin (FOM), cefazolin (CEZ), cefmetazole (CMZ), cefotiam (CTM) and piperacillin (PIPC) against clinical isolates of methicillin-sensitive Staphylococcus aureus (MSSA) (beta-lactamase-producing or non-producing) and methicillin-sensitive coagulase-negative Staphylococci (MSCNS) (beta-lactamase-producing or non-producing) were determined to make clear the differences in antimicrobial activity of FOM and beta-lactam antibiotics. The antimicrobial activity of PIPC against beta-lactamase-producing strains of MSSA was lower than that against non-producing ones, judging from the distribution patterns of susceptibility of the strains to PIPC. There were no differences in the antimicrobial activity of FOM, CEZ and CMZ for the producing and non-producing strains. The activity of FOM against MSCNS was comparable to that against MSSA, although those of CEZ, CMZ, CTM and PIPC were decreased. FOM, CEZ, CMZ and CTM showed bactericidal activity against TH4278 (MIC [microgram/ml]: FOM, 1; CEZ, 0.5; CMZ, 1; CTM, 0.5; PIPC, 1) of beta-lactamase-producing MSSA at 1 microgram/ml for 6 h, but PIPC did not at the same condition. FOM and CMZ at MIC suppressed regrowth of the strain, but CEZ, CTM and PIPC did not. In conclusion, FOM, which is not affected by beta-lactamase, demonstrated strong bactericidal activity at low concentration against the beta-lactam-resistant strains due to beta-lactamase production.     

Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli

Silver nanoparticles (Ag-NPs) have been known to have inhibitory and bactericidal effects. Resistance to antimicrobial agents by pathogenic bacteria has emerged in recent years and is a major health problem. The combination effects of Ag-NPs with the antibacterial activity of antibiotics have not been studied. Here, we report on the synthesis of metallic nanoparticles of silver using a reduction of aqueous Ag(+) ion with the culture supernatants of Klebsiella pneumoniae. Also in this article these nanoparticles are evaluated for their part in increasing the antimicrobial activities of various antibiotics against Staphylococcus aureus and Escherichia coli. The antibacterial activities of penicillin G, amoxicillin, erythromycin, clindamycin, and vancomycin were increased in the presence of Ag-NPs against both test strains. The highest enhancing effects were observed for vancomycin, amoxicillin, and penicillin G against S. aureus.     

In vitro activity of levofloxacin against coagulase-positive and -negative staphylococci.

The in vitro activity of levofloxacin compared with that of ciprofloxacin, ofloxacin and norfloxacin were examined by conventional in vitro tests against 150 clinical isolates of staphylococci, subdivided according to species and susceptibility to methicillin. Although the minimum inhibitory concentrations (MICs) of all quinolones were highest in methicillin-resistant Staphylococcus aureus strains, the activity of levofloxacin was almost complete in methicillin-resistant S. epidermidis and methicillin-resistant S. haemolyticus when compared with ciprofloxacin and ofloxacin, which showed more than 30% resistance. Methicillin-susceptible S. aureus and S. epidermidis strains were susceptible to all quinolones with few differences between the antibiotics tested. The minimal bactericidal activity of levofloxacin was within the double dilution range of MIC values for all strains tested, demonstrating its potent role against staphylococci. In time-kill studies, levofloxacin exerted bactericidal activity within 3 h against all staphylococci. These in vitro results suggest that levofloxacin is a potent fluoroquinolone against coagulase-negative staphylococci and that it is both methicillin-susceptible and resistant. Further studies are necessary to determine the role of this drug in the treatment of infections sustained by these microorganisms.     

In vitro activity of fosfomycin combined with rifampin, pefloxacin and imipenem against staphylococci: a study by the time-kill curve method

The in vitro activity of fosfomycin alone and in combination with rifampin, pefloxacin and imipenem was studied by the time-kill method against staphylococci. Fosfomycin, pefloxacin and imipenem used at concentrations within the therapeutic range, exerted a bactericidal effect, whereas rifampin acted as a bacteriostatic drug. The combination of fosfomycin and rifampin was found to be antagonistic against rifampin-susceptible strains and indifferent for rifampin-resistant isolates. Fosfomycin combined with pefloxacin usually produced an indifferent effect. The interaction between fosfomycin and imipenem was mainly indifferent but synergism occurred with methicillin-resistant strains and antagonism was observed for one methicillin-susceptible isolate of Staphylococcus aureus.     

Improved efficacy with nonsimultaneous administration of netilmicin and minocycline against methicillin-resistant Staphylococcus aureus in in vitro and in vivo models

The effect of combined administration of netilmicin and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) was investigated by using in vitro and in vivo models. Thirty one isolates of MRSA were tested for sensitivity to netilmicin, minocycline, and combination of both by the chequer board method. We used then a dynamic in vitro system, which simulates in vivo serum kinetics, to assess the effect of various combination regimens of these antibiotics against an MRSA isolate with a fractional inhibitory concentration index of 0.25. The following dose regimens were compared: netilmicin given alone; minocycline given alone; both antibiotics given simultaneously; netilmicin followed by minocycline at 2 h; or minocycline followed by netilmicin at 2 h. Netilmicin showed a stronger activity than minocycline. On the other hand, their combination was synergistic against 19% of isolates and additive against 77% of isolates. Against one isolate only, it was indifferent, and no antagonism was observed. In the auto-simulation system, the combination of antibiotics was generally more effective than single drugs, with the regimen netilmicin followed by minocycline at 2 h showing the highest antibacterial effect. In the mouse model of pulmonary infection, the bacterial counts and histopathological findings of the lungs improved by treatment with this regimen. This regimen led also to a significantly high survival rate of mice with systemic infection compared to the other treatment regimens. Therefore, it was concluded that administration of netilmicin followed by minocycline at 2 h may be an effective combination against MRSA infection.     

2016—2018年河南某医院临床分离菌分布及耐药性分析

目的 了解河南省胸科医院2016—2018年临床常见标本细菌分布及对常用抗菌药物的敏感性和耐药性,为合理使用抗菌药物提供依据。方法 收集该院2016年1月—2018年12月临床分离细菌,采用全自动细菌鉴定药敏仪或纸片扩散法进行抗菌药物的敏感性试验,按照2018年CLSI M100标准判断结果,数据统计分析采用WHONET 5.6软件。结果 3年间共检出临床分离菌4421株,其中革兰阳性细菌702株(15.9%),革兰阴性菌3719株(84.1%)。金黄色葡萄球菌和凝固酶阴性葡萄球菌耐甲氧西林株(MRSA和MRCNS)平均检出率分别为59.1%和85.9%,葡萄球菌属中尚未检出对万古霉素、替考拉宁耐药的菌株。粪肠球菌对多数抗菌药物的耐药性低于屎肠球菌,未发现对万古霉素的耐药的粪肠球菌,但是发现1株耐万古霉素的屎肠球菌。3年间检出耐碳青霉烯类肠杆菌科细菌平均检出率为16.5%(281/1703);碳青霉烯耐药的肺炎克雷伯菌和大肠埃希菌平均检出率分别为24.9%(221/889)和2.2%(4/181);耐碳青霉烯类铜绿假单胞菌平均检出率为15.7%(110/700);耐碳青霉烯类鲍曼不动杆菌平均检出率为57.1%(237/415)。ICU分离出的肠杆菌科细菌和非发酵细菌的耐药率普遍高于非ICU分离细菌。结论 该院耐碳青霉烯类肺炎克雷伯菌检出率较高,细菌耐药性形势已十分严峻,应加强抗菌药物的合理使用和感控措施,同时应做好细菌耐药监测工作。