Dosing strategies to optimize currently available anti-MRSA treatment options (Part 2: PO options)

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen in both outpatient and inpatient settings. Research to optimize the dosing of these agents is needed to slow the development of antimicrobial resistance and to decrease the likelihood of clinical failure.

Areas covered: This review summarizes the available data for orally administered antimicrobials routinely used as monotherapy for MRSA infections. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 – Present) search was performed to identify relevant literature for this review.

Expert commentary: There is a vast divide in the amount of pharmacokinetic/pharmacodynamic data to guide dosing decisions for older MRSA agents compared with the oxazolidenones.

Five-year view: Additional retrospective data will become available for the older MRSA agents in severe MRSA infections.     

一种快速检测耐甲氧西林金黄色葡萄球菌方法的评价

目的评价胶体金法检测耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)临床应用价值。方法采用头孢西丁纸片扩散法、PCR扩增mecA基因和胶体金法对临床分离的150株金黄色葡萄球菌(100株MRSA和50株MSSA)、68株溶血葡萄球菌(58株MRSH和10株MSSH)、135株表皮葡萄球菌(97株MRSE和38株MSSE)进行检测并作比较。结果 MRSA、MSSA、MRSE、MSSE、MSSH三种方法检测结果一致。58株MRSH中6株胶体金法检测阴性。结论胶体金法可作为MRSA简便而准确的检测方法,同时也可分析MRCNS。     

Influenza-associated bacterial pathogens in patients with 2009 influenza A (H1N1) infection: impact of community-associated methicillin-resistant Staphylococcus aureus in Queensland, Australia

Background: Secondary bacterial pneumonia due to community onset methicillin‐resistant Staphylococcus aureus (MRSA) has become a highly publicised cause of influenza‐associated death. There is a risk that case reports of fatal outcomes with post‐influenza MRSA pneumonia may unduly influence antibiotic prescribing. Aims: The aim of this study was to demonstrate the incidence of community‐onset MRSA pneumonia in 2009 H1N1 influenza patients. Methods: The microbiology records of patients positive for influenza A (H1N1) in 2009 were reviewed for positive blood or respiratory tract cultures and urinary pneumococcal antigen results within a Queensland database. Patients with such positive results within 48 h of hospital admission and a positive H1N1 influenza result in the prior 6 weeks were included. Results: In 2009, 4491 laboratory‐confirmed pandemic influenza A (H1N1) infections were detected. Fifty patients (1.1% of the H1N1 cohort) who were hospitalised with H1N1 and who had a bacterial respiratory tract pathogen were identified. Streptococcus pneumoniae (16 patients; 32%), Staphylococcus aureus (13 patients; 26%) and Haemophilus influenzae (9 patients; 18%) were the most commonly cultured organisms. Of the cohort of 4491 patients, MRSA was detected in only two patients, both of whom were admitted to intensive care units and survived after prolonged admissions. Conclusions: Influenza‐associated community‐onset MRSA pneumonia was infrequently identified in the 2009 H1N1 season in Queensland, despite community‐onset MRSA skin and soft tissue infections being very common. Although post‐influenza MRSA pneumonia is of great concern, its influence on empiric‐prescribing guidelines should take into account its incidence relative to other secondary bacterial pathogens.     

Inducible clindamycin resistance in Staphylococcus aureus isolated from clinical samples

Purpose: Clindamycin is commonly used in the treatment of erythromycin resistant Staphylococcus aureus causing skin and soft tissue infections. In vitro routine tests for clindamycin susceptibility may fail to detect inducible clindamycin resistance due to erm genes resulting in treatment failure, thus necessitating the need to detect such resistance by a simple D test on routine basis. Materials and Method: 247 Staphylococcus aureus isolates were subjected to routine antibiotic susceptibility testing including oxacillin (1μg) by Kirby Bauer disc diffusion method. Inducible clindamycin resistance was detected by D test, as per CLSI guidelines on erythromycin resistant isolates. Results: 36 (14.5%) isolates showed inducible clindamycin resistance, nine (3.6%) showed constitutive resistance while remaining 35 (14.1%) showed MS phenotype. Inducible resistance and MS phenotype were found to be higher in MRSA as compared to MSSA (27.6%, 24.3% and 1.6%, 4% respectively). Conclusion: Study showed that D test should be used as a mandatory method in routine disc diffusion testing to detect inducible clindamycin resistance.     

2000-2003年广州地区耐甲氧西林金黄色葡萄球菌耐药变迁及治疗对策

目的了解广州地区12家医院临床分离的耐甲氧西林金黄色葡萄球菌（MRSA）的耐药现状及动态变化情况，为临床治疗提供对策。方法严格按NCCLS标准用K—B法对2000—2003年自广州地区12家医院临床分离出的1247株金黄色葡萄球菌进行微生物药物敏感性试验检测。结果1．2000—2003年每年的MRSA的检出率分别为50．8％（154／303）、65．0％（195／300）、61．1％（228／373）、70．8％（192／271），结果差异显著（P〈0．001）。2．2000—2003年MRSA对受试的7种抗生素的敏感率分别为环丙沙星（CIP）22．1—40．0％、四环素（TET）35．1—50．3％、红霉素（ERY）12．0—18．9％、万古霉素（VAN）100．0％、克林霉素（CLI）45．8—68．2％、庆大霉素（GEN）20．2—40．1％、青霉素（PEN）0．0％，其中CLI、CIP、GEN的耐药性在四年间差异显著（P〈0．001），而其他的几种抗生素均无差异（P〉0．05），未发现耐万古霉素的MRSA。结论VAN是治疗MRSA感染的首选经验用药，为控制MRSA感染的发生，临床应合理使用抗生素。     

猪源耐甲氧西林金黄色葡萄球菌的耐药表型及其SCCmec基因分型研究

目的 了解上海猪场及屠宰场耐甲氧西林金黄色葡萄球菌(MRSA)的流行状况、耐药谱特征及其SCCmec基因分型特点。方法 我们于2011年8月—2012年5月分别在上海市5个规模化猪场和1个屠宰场,采集猪鼻腔拭子样品共计232份。通过7.5%氯化钠肉汤预增菌,显色培养基显色培养分离金黄色葡萄球菌(SA),采用双重PCR方法扩增其中是否含有nuc基因和mecA基因进行MRSA鉴定;以肉汤稀释法进行药物敏感性试验;应用多重PCR方法进行SCCmec基因分型;同时检测杀白细胞素(PVL)基因。结果 共计分离得到139株SA,其中70株MRSA,MRSA的检出率为30.2%(70/232)。基因分型显示均为SCCmecⅣb型,未检测到PVL基因,药敏结果显示MRSA除对利奈唑胺,万古霉素,阿米卡星全部敏感外,对头孢噻呋,庆大霉素,诺氟沙星耐药率分别为74.3%,62.9%和42.9%,对阿奇霉素,红霉素,氟苯尼考,氯霉素,苯唑西林的耐药率均为100%,值得注意的,本研究中分离的全部MRSA都对截短侧耳类药物泰妙菌素、沃尼妙林以及人医新药瑞他帕林表现高水平耐药。结论 结果显示了上海地区猪源MRSA主要流行SCCmecⅣb型,并且具有多重耐药的特点,尤其对截断侧耳类人医新药全部耐药,这也提示我们要防控动物源耐药菌或耐药基因通过食物链或者环境向人类的传播的潜在风险。     

Failure of bacteriophage typing to detect an inter-hospital outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in Zagreb subsequently identified by random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE)

Objective: To establish the extent of inter-hospital spread of methicillin-resistant Staphylococcus aureus (MRSA) in Zagreb and to determine the most suitable method for typing local strains.
Methods: We analyzed a collection of 33 MRSA isolates from three Zagreb hospitals together with five unrelated British MRSA isolates by antibiogram typing, bacteriophage typing, randomly amplified polymorphic DNA (RAPD) analysis and pulsed-field gel electrophoresis (PFGE) after digestion with Smal restriction endonuclease. Bacteriophage typing was done with the international set of S. aureus typing phages. RAPD and PFGE profiles were analyzed visually and by using the 'GelCompar' computer program.
Results: Antibiogram typing provided eight profiles. Thirty (91%) of the 33 Croatian strains of MRSA were non-typable by phage typing. Visual analysis of RAPD products identified six, and visual analysis of PFGE fragments nine, distinct profiles. Computer analysis of RAPD data separated British isolates from the Croatian ones, but did not cluster the visually determined RAPD types. PFGE computer analysis separated British isolates and clustered isolates in concordance with visual interpretation. Thirty-one of the 38 isolates (82%) were visually grouped in the same clusters by both molecular methods. The dominant strain was present in each of the three hospitals.
Conclusions: Bacteriophage typing was unhelpful for the analysis of Croatian MRSA, since most strains were untypable with the international set of bacteriophages. RAPD and PFGE were more successful in typing the organisms and showed evidence of inter-hospital spread of one predominant MRSA strain in all three Zagreb hospitals. Thus RAPD and PFGE proved to be a useful aid in elucidating the epidemiology of MRSA infection in Zagreb hospitals and should be established in Croatia for typing MRSA.