Vancomycin-resistant Staphylococcus aureus: no apocalypse now

The number of reports concerning vancomycin-resistant Staphylococcus aureus is much higher than the number of true resistant strains or unexpected clinical failures. Many confounding factors, including inadequate serum levels, severely ill patients, foreign devices or undrained abscesses, are more likely to be responsible for the clinical failures than resistance to vancomycin.     

Low prevalence of methicillin-resistant Staphylococcus aureus with reduced susceptibility to glycopeptides in Belgian hospitals

Staphylococcus aureus strains with decreased susceptibility to glycopeptides (GISA) have been associated with increased risk of glycopeptide treatment failure. To assess the prevalence of these strains in hospitalised patients in Belgium, 455 methicillin-resistant S. aureus (MRSA) isolates collected in 2001 were screened by two assays: (i) growth on vancomycin agar screen (VAS; brain heart infusion agar (BHI) + vancomycin 6 mg/L); and (ii) a synergy/antagonism test with aztreonam/cefazolin on Mu3 agar (BHI + vancomycin 3 mg/mL). Isolates growing on VAS or Mu3 agar were characterised further by analysis of population susceptibility profiles. MICs of glycopeptides were determined by agar dilution, broth microdilution and Etest (low and high inocula) methods. The isolates were genotyped by pulsed-field gel electrophoresis (PFGE) and determination of staphylococcal cassette chromosome mec (SCCmec) type. No GISA isolates were found. Three (0.7%) hetero-vancomycin intermediate S. aureus (hVISA) and ten (2.2%) hetero-teicoplanin intermediate S. aureus (hTISA) isolates were identified by population analysis. All but one hetero-GISA isolate belonged to either epidemic PFGE group A/SCCmec type I (69%) or PFGE group D/SCCmec type I (23%), both of which were resistant to gentamicin. The sensitivity and specificity for the detection of hetero-GISA by the two assays were 15.4% and 99.8%, respectively, for VAS, and 84.6% and 95.9%, respectively, for Mu3. The data indicated that hetero-GISA strains were uncommon among Belgian MRSA isolates from hospitalised patients. Use of Mu3 agar was more sensitive, but less specific, than VAS as a screening method.     

False synergy between vancomycin and β-lactams against glycopeptide-intermediate Staphylococcus aureus (GISA) caused by inappropriate testing methods

The combination of vancomycin and beta-lactams is often considered synergistic and has been recommended for the treatment of glycopeptide-intermediate Staphylococcus aureus (GISA) infections. In this study, the combination of vancomycin or teicoplanin with different beta-lactams was tested. When using NaCl 4% w/v, for better expression of heterogeneous resistance to beta-lactams, with a longer (48-h) incubation period and a higher (10(7) CFU/mL) inoculum, the association of vancomycin with beta-lactams was antagonistic. However, a synergistic effect was observed for teicoplanin under the same conditions.     

Incidence of Staphylococcus aureus with reduced susceptibility to glycopeptides in two French hospitals

Objectives   To determine the incidence of Staphylococcus aureus isolates with reduced susceptibility to glycopeptides among all clinical isolates collected consecutively in two French hospitals between November 1998 and April 1999.
Methods   Methicillin-resistant and -susceptible S. aureus isolates were screened on vancomycin- or teicoplanin-supplemented agar plates. Glycopeptide MICs were determined by the E test procedure with a high inoculum and by an agar dilution technique. Glycopeptide-intermediate S. aureus isolates were identified as homogeneously or heterogeneously resistant to vancomycin by performing population analysis.
Results   Of the 640 isolates recovered from 518 patients, three from the same patient and two from two different patients showed homogeneous or heterogeneous intermediate resistance to vancomycin.
Conclusion   The incidence of glycopeptide-intermediate S. aureus (homogeneously or heterogeneously resistant) in a non-selected patient population, i.e. regardless of predisposing factors and glycopeptide therapeutics, remains low in the two French hospitals involved in the study, representing 0.6% of isolates.     

Heteroresistance: a concern of increasing clinical significance?

Recent studies have focused on issues related to heteroresistance, including its definition, methods of detection and frequency. Most such studies have reported data concerning infections caused by Staphylococcus aureus, but the clinical significance of heteroresistance is unclear. Six studies have described infections caused by S. aureus strains that were heteroresistant to vancomycin, with two suggesting an association between the emergence of heteroresistance and treatment failure or mortality, and four suggesting no such association. Further studies are required to evaluate the clinical implications of heteroresistance in an era in which rates of antimicrobial resistance are increasing alarmingly worldwide.     

Incidence of glycopeptide hetero-intermediate Staphylococcus aureus strains in Maltese hospitals

The incidence of hetero-intermediate glycopeptide susceptibility among Staphylococcus aureus isolates in Malta, a country with a high incidence of methicillin resistance, was studied by screening 454 non-repetitive S. aureus isolates on teicoplanin-supplemented agar plates, followed by Etests and genotypic studies. All strains were susceptible to vancomycin, but four (0.88%) exhibited teicoplanin MICs of > 12 mg/L. High methicillin-resistant S.aureus endemicity was not an accurate predictor of the emergence of non-susceptibility to glycopeptides.     

Synergistic effect of vancomycin combined with cefotaxime,imipenem, or meropenem against Staphylococcus aureus with reduced susceptibility to vancomycin

Background/aim We investigated the synergistic effect between vancomycin and β-lactams against vancomycin-susceptible (VSSA) and nonsusceptible MRSA isolates [heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA].Materials and methods A total of 29 MRSA, including 6 VISA, 14 hVISA, and 9 VSSA isolates, were subjected to a microbroth dilution-minimum inhibitory concentration (MIC) checkerboard using vancomycin combined with cefotaxime, imipenem, or meropenem. To confirm synergistic activity, the representative strains of VISA, hVISA, and VSSA were then selected for the time-kill curve method.Results The combination of vancomycin with imipenem, meropenem, or cefotaxime exhibited synergistic effects against 17 (2 VISA, 9 hVISA, and 6 VSSA), 14 (3 VISA, 9 hVISA and 2 VSSA), and 5 (3 VISA and 2 hVISA) isolates, respectively. Additive and indifferent effects were found in the remaining isolates, but no antagonistic effect was observed. Using time-kill assay, the vancomycin combined with either imipenem or cefotaxime demonstrated synergism against both VISA and hVISA isolates, while the synergistic effect with meropenem was obtained only in the VISA isolates.Conclusion This study demonstrated in vitro enhanced antibacterial activity of vancomycin plus β-lactams against clinical hVISA or VISA isolates. These combinations may be an alternative treatment for MRSA infections in clinical practice.     

光动力抗微生物化学疗法修复骨髓炎模型兔的实验

背景:光动力抗微生物化学疗法具有广谱抗菌、起效快和无耐药的特点,目前已被广泛应用于浅表局限性感染的治疗。目的:了解光动力抗微生物化学疗法治疗骨髓炎的效果。方法:取新西兰大白兔(中国人民解放军军事医学科学院实验动物中心提供)36只,建立左侧胫骨骨髓炎模型,造模28 d后随机分3组处理:空白组胫骨开窗清创后不做任何处理;对照组胫骨开窗清创后在感染胫骨骨髓腔内填入万古霉素聚甲基丙烯酸甲酯骨水泥;实验组胫骨开窗清创后对感染胫骨骨髓腔进行光动力抗微生物化学治疗。术后4,8,12周,分别进行大体观察、影像学检查及细菌培养。实验已通过武警后勤学院附属医院伦理委员会批准[(2015)-0002]。结果与结论:①大体皮肤外观:空白组可见脓性分泌物,实验组与对照组脓性分泌物消失,皮肤愈合良好;②X射线检查:随着时间的延长,空白组骨髓炎逐渐加重,实验组及对照组治疗后骨质破坏逐渐减少,骨质缺损逐渐愈合,实验组与对照组术后不同时间点的表现无差异;③细菌培养:随着时间的延长,空白组细菌阳性率无明显变化,实验组及对照细菌组阳性率逐渐下降,且实验组与对照组术后不同时间点的细菌阳性率比较差异无显著性意义(P>0.05);④结果表明:光动力抗微生物化学疗法作为一种新型的治疗骨髓炎方法,可有效控制感染,为骨髓炎临床治疗积累了实验依据。     

Vancomycin intermediate resistant Staphylococcus aureus in the nasal cavity of asymptomatic individuals: a potential public health challenge

BackgroundThe potential of transmitting multidrug resistant Staphylococcus aureus from asymptomatic individuals to healthy individuals could constitute a great challenge to antimicrobial therapy.MethodsThe antibiograms of the S. aureus from asymptomatic individuals were determined by disk diffusion and agar dilution assay techniques with different antibiotics and vancomycin.ResultsOf the 152 S. aureus isolated, (59)38.8% isolates were multi-drug resistant strains. Streptomycin was the most effective and inhibited (135)88.82% of the isolates while ceftazidime inhibited (24)15.8% of the isolates. While (82)54.0% of the isolates inhibited by cefuroxime had resistant colonies within their inhibition zones (Rc) and ofloxacin inhibited (100)65.8% of the isolates without having resistant colonies within the inhibition zones, ceftazidime inhibited (7)4.6% of the isolates with resistant colonies within the inhibition zones. Subjecting the isolates to vancomycin showed that (27)17.8% were resistant to 2 µg/ml, (43)28.3% were resistant to 4 µg/ml and (27)17.8% of the isolates were simultaneously resistant to both concentrations of vancomycin. Although (100)65.8% of the isolates had MAR_index ≥0.2, (52)34.2% of the isolates had MAR_index ≤ 0.2 and (65)428% of the isolates were considered multidrug resistant strains.ConclusionThe isolation of multi-drug and vancomycin intermediate resistant strains of S. aureus in high percentage, in this study, presents a great threat to clinicians and general populace. The vancomycin intermediate resistant S. aureus (VISA) in asymptomatic individuals could be a critical concern to the therapeutic dilemma to be added to the presence of multi-drug resistance. A more sustainable therapy must be in place to prevent its dissemination or the outbreak of its infection.     

Daptomycin non-susceptible Staphylococcus aureus at a US medical centre

Daptomycin non-susceptible Staphylococcus aureus was rarely encountered at our medical centre until 2010, when 10 isolates (0.4% of S. aureus) were confirmed by E-test as non-susceptible. These isolates were not of the same strain type and there was no link between the 10 patients. Daptomycin non-susceptibility may be increasing.     

CHID1 positively regulates RLR antiviral signaling by targeting the RIG-I/VISA signalosome

Retinoic acid-inducible gene-I (RIG-I) belongs to the RIGI-like receptors (RLRs), a class of primary pattern recognition receptors. It senses viral double-strand RNA in the cytoplasm and delivers the activated signal to its adaptor virus-induced signaling adapter (VISA), which then recruits the downstream TNF receptor-associated factors and kinases, triggering a downstream signal cascade that leads to the production of proinflammatory cytokines and antiviral interferons (IFNs). However, the mechanism of RIG-I-mediated antiviral signaling is not fully understood. Here, we demonstrate that chitinase domain-containing 1 (CHID1), a member of the chitinase family, positively regulates the RLR antiviral signaling pathway by targeting the RIG-I/VISA signalosome. CHID1 overexpression enhances the activation of nuclear factor κB (NF-кB) and interferon regulatory factor 3 (IRF3) triggered by Sendai virus (SeV) by promoting the polyubiquitination of RIG-I and VISA, thereby potentiating IFN-β production. CHID1 knockdown in human 239T cells inhibits SeV-induced activation of IRF3 and NF-κB and the induction of IFN-β. These results indicate that CHID1 positively regulates RLR antiviral signal, revealing the novel mechanism of the RIG-I antiviral signaling pathway.     

Vancomycin MIC creep in methicillin-resistant Staphylococcus aureus (MRSA) isolates from 2006 to 2010 in a hospital in China

Purpose: To assess whether vancomycin minimum inhibitory concentration (MIC) creeps among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in a regional hospital in China. Furthermore, to analyze the causes of vancomycin MIC creeps and the relationship between vancomycin MICs and the outcome among patients with MRSA infection. Materials and Methods: All clinical isolates of MRSA from 2006-2010 were retrieved and tested by the broth microdilution procedure to determine their vancomycin MIC. Meanwhile, related patient records were analyzed. Results: While all isolates were susceptive to vancomycin, the percentage of isolates with a vancomycin MIC = 1 mg/L increased significantly from 2006 (37.0%) to 2010 (75.7%). Meanwhile, vancomycin usage density (DDDs/1000 bed-days) had increased significantly from 2006-2010. Mean linear correlation analysis showed a statistically significant positive correlation (r = 0.905, P < 0.05) between the consumption of vancomycin and the percentage of MRSA isolates with a vancomycin MIC = 1 mg/L. Clinical records revealed high vancomycin MIC was associated with a higher microbiologic failure rate in MRSA bloodstream infections. Conclusions: The data demonstrated vancomycin MIC creep among clinical isolates in our hospital, and the MIC creep may be caused by the increasing usage of vancomycin. Furthermore, the analysis strongly suggested this shift of vancomycin MIC within the susceptible range may be associated with an increasing probability of treatment failure.     

Methicillin‐resistant and vancomycin‐intermediate Staphylococcus aureus colonizing patients and intensive care unit environment: virulence profile and genetic variability

This study aims to determine the prevalence of Staphylococcus aureus colonizing patients and ICU environment of a teaching hospital, the virulence and antimicrobial susceptibility profile of the isolates, and to evaluate the genetic relationship among them. A total of 536 swabs (134 of patients and 402 of ICU environment) were collected and analyzed to detect S. aureus. The antimicrobial susceptibility of the isolates was determined by disk diffusion test, and the detection of the mecA and virulence factors genes was performed by PCR, in addition to SCCmec typing. The genetic similarity of the isolates was determined by PFGE. Staphylococcus aureus was isolated in 12.7% of the swabs. The prevalence of colonization was 13.4% in patients and 12.4% in the environmental samples. The multidrug resistance was determined in 82.4% of the isolates. The prevalence of methicillin‐resistant S. aureus was 20.6%, with 50.0% classified as SCCmec IV. The intermediate resistance to vancomycin was detected in 5.9% and 4.4% of the isolates obtained from patients and environment, respectively. Identical isolates obtained from different patients and sources were grouped into several clusters. The results showed dissemination of multidrug‐resistant strains between patients and fomites and the persistence of MRSA and VISA isolates in the ICU environment.     

Differences in daptomycin and vancomycin ex vivo behaviour can lead to false interpretation of negative blood cultures

In clinical studies on bacteraemia, the negativity of blood cultures is an important endpoint for comparing the efficacy of different therapeutic regimens. In FAN^° anaerobic blood culture medium (BacT/ALERT system), daptomycin displayed increased MIC against Staphylococcus aureus and improved abolishment of its carryover effect in charcoal when compared with vancomycin. Differences between these two drugs can lead to a false interpretation of negative blood cultures. To compare different antibiotic regimens for the treatment of bacteraemia, preliminary studies are mandatory to ensure that ex vivo antibiotic behaviour is similar in the blood-culture system used.