Methicillin-Resistant, Vancomycin-Intermediate and Vancomycin-Resistant Staphylococcus aureus Infections in Solid Organ Transplantation
2013; Elsevier BV; Volume: 13; Linguagem: Inglês
10.1111/ajt.12098
ISSN1600-6143
AutoresChristian Garzoni, Paschalis Vergidis,
Tópico(s)Antibiotics Pharmacokinetics and Efficacy
ResumoStaphylococcus aureus is a major cause of infection among solid-organ transplant recipients. After years of rising incidence, methicillin-resistant S. aureus (MRSA) infections have been decreasing. In the United States, the incidence of MRSA catheter-associated bloodstream infections has declined (1Burton DC Edwards JR Horan TC Jernigan JA Fridkin SK Methicillin-resistant Staphylococcus aureus central line-associated bloodstream infections in US intensive care units, 1997–2007.JAMA. 2009; 301: 727-736Crossref PubMed Scopus (216) Google Scholar) as have rates of invasive healthcare-associated MRSA infections (2Kallen AJ Mu Y Bulens S et al.Health care-associated invasive MRSA infections, 2005–2008.JAMA. 2010; 304: 641-648Crossref PubMed Scopus (366) Google Scholar). Data from Europe are even more encouraging (3Kock R Becker K Cookson B et al.Methicillin-resistant Staphylococcus aureus (MRSA): Burden of disease and control challenges in Europe.Euro Surveill. 2010; 15: 19688Crossref PubMed Scopus (419) Google Scholar). According to the European Antimicrobial Resistance Surveillance System (EARSS), invasive MRSA infections are decreasing in nine countries (4European Centre for Disease Prevention and ControlAnnual Epidemiological Report on Communicable Diseases in Europe 2010.. ECDC, Stockholm2010Google Scholar). According to the HELICS surveillance network, the incidence of MRSA infections has decreased in the intensive care setting (5European Centre for Disease Prevention and ControlAnnual Epidemiological Report on Communicable Diseases in Europe 2009.. ECDC, Stockholm2009Google Scholar). Those data support the use of aggressive policies in infection prevention and control. Despite those positive data, MRSA still accounts for more than 25% of bacteremias caused by S. aureus in many European countries (4European Centre for Disease Prevention and ControlAnnual Epidemiological Report on Communicable Diseases in Europe 2010.. ECDC, Stockholm2010Google Scholar). However, among central venous catheter-associated bloodstream infections caused by S. aureus in United States intensive care units (ICUs), more than 50% are caused by MRSA (6Hidron AI Edwards JR Patel J et al.NHSN annual update: Antimicrobial-resistant pathogens associated with healthcare-associated infections: Annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007.Infect Control Hosp Epidemiol. 2008; 29: 996-1011Crossref PubMed Scopus (1656) Google Scholar). Thus, further efforts to decrease infection are needed. S. aureus is a Gram-positive organism frequently causing infection following transplantation. It is commonly encountered within the first 3 posttransplant months. A significant number of those infections are caused by MRSA. S. aureus is one of the leading causes of Gram-positive bacteremia among transplant recipients reported in up to 25% of all isolated bacterial pathogens (7Bert F Larroque B Paugam-Burtz C et al.Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients: An analysis of 259 episodes.Liver Transpl. 2010; 16: 393-401Crossref PubMed Scopus (93) Google Scholar, 8Lee SO Kang SH Abdel-Massih RC Brown RA Razonable RR Spectrum of early-onset and late-onset bacteremias after liver transplantation: Implications for management.Liver Transpl. 2011; 17: 733-741Crossref PubMed Scopus (61) Google Scholar, 9Malinis MF Mawhorter SD Jain A Shrestha NK Avery RK van Duin D Staphylococcus aureus bacteremia in solid organ transplant recipients: Evidence for improved survival when compared with nontransplant patients.Transplantation. 2012; 93: 1045-1050Crossref PubMed Scopus (36) Google Scholar, 10Singh N Wagener MM Obman A Cacciarelli TV de Vera ME Gayowski T Bacteremias in liver transplant recipients: Shift toward gram-negative bacteria as predominant pathogens.Liver Transpl. 2004; 10: 844-849Crossref PubMed Scopus (142) Google Scholar). S. aureus is a common cause of pneumonia after lung transplantation with rates of MRSA infection ranging from 40% to 80% in staphylococcal pneumonia (11Bonatti H Pruett TL Brandacher G et al.Pneumonia in solid organ recipients: Spectrum of pathogens in 217 episodes.Transplant Proc. 2009; 41: 371-374Crossref PubMed Scopus (38) Google Scholar, 12Gupta MR Valentine VG Walker JE et al.Clinical spectrum of gram-positive infections in lung transplantation.Transpl Infect Dis. 2009; 11: 424-431Crossref PubMed Scopus (26) Google Scholar, 13Manuel O Lien D Weinkauf J Humar A Cobos I Kumar D Methicillin-resistant Staphylococcus aureus infection after lung transplantation: 5-year review of clinical and molecular epidemiology.J Heart Lung Transplant. 2009; 28: 1231-1236Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar). Surgical site infections following transplantation are also commonly caused by S. aureus. The true extent of MRSA colonization and incidence of infection after transplantation in adults and children varies among transplant centers reflecting the type of transplanted organs and the prevalence of carriage and infection in the nontransplant patient population. Risk factors associated with MRSA infection include prolonged hospital stay, exposure to broad-spectrum antibiotics, admission to an ICU or burn unit, recent surgery, close contact to other patients with MRSA, presence of foreign bodies such as central venous catheters, and MRSA colonization (14Asensio A Guerrero A Quereda C Lizan M Martinez-Ferrer M Colonization and infection with methicillin-resistant Staphylococcus aureus: Associated factors and eradication.Infect Control Hosp Epidemiol. 1996; 17: 20-28Crossref PubMed Scopus (155) Google Scholar). Factors specifically noted in liver transplant recipients include surgery within 2 weeks prior to infection, cytomegalovirus seronegativity or primary infection, extended posttransplant ICU stay, presence of other major posttransplant infections, peritonitis and increased prothrombin time (15Singh N Paterson DL Chang FY et al.Methicillin-resistant Staphylococcus aureus: The other emerging resistant Gram-positive coccus among liver transplant recipients.Clin Infect Dis. 2000; 30: 322-327Crossref PubMed Scopus (128) Google Scholar, 16Bert F Bellier C Lassel L et al.Risk factors for Staphylococcus aureus infection in liver transplant recipients.Liver Transpl. 2005; 11: 1093-1099Crossref PubMed Scopus (63) Google Scholar, 17Florescu DF McCartney AM Qiu F et al.Staphylococcus aureus infections after liver transplantation.Infection. 2011; Google Scholar). Patients on the waiting list and transplant recipients have an increased risk of becoming colonized with MRSA because of their illness and contact with the healthcare system. High rates of colonization have been reported for those undergoing hemodialysis (18Johnson LB Jose J Yousif F Pawlak J Saravolatz LD Prevalence of colonization with community-associated methicillin-resistant Staphylococcus aureus among end-stage renal disease patients and healthcare workers.Infect Control Hosp Epidemiol. 2009; 30: 4-8Crossref PubMed Scopus (48) Google Scholar) and patients with cystic fibrosis (19Stone A Quittell L Zhou J et al.Staphylococcus aureus nasal colonization among pediatric cystic fibrosis patients and their household contacts.Pediatr Infect Dis J. 2009; 28: 895-899Crossref PubMed Scopus (30) Google Scholar). Patients can become colonized following transplantation, as shown among liver transplant recipients (20Santoro-Lopes G de Gouvea EF Monteiro RC et al.Colonization with methicillin-resistant Staphylococcus aureus after liver transplantation.Liver Transpl. 2005; 11: 203-209Crossref PubMed Scopus (33) Google Scholar). MRSA acquisition is dependent on the local MRSA prevalence, infection control policies and the recipient's general state of illness (21Singh N Squier C Wannstedt C Keyes L Wagener MM Cacciarelli TV Impact of an aggressive infection control strategy on endemic Staphylococcus aureus infection in liver transplant recipients.Infect Control Hosp Epidemiol. 2006; 27: 122-126Crossref PubMed Scopus (63) Google Scholar). Methicillin-susceptible and -resistant S. aureus colonization has been shown to increase the risk of subsequent infection (22Wertheim HF Melles DC Vos MC et al.The role of nasal carriage in Staphylococcus aureus infections.Lancet Infect Dis. 2005; 5: 751-762Abstract Full Text Full Text PDF PubMed Scopus (1779) Google Scholar), which is usually caused by the same strain. Among transplant patients specific data exist only for liver recipients. Liver transplant recipients colonized with MRSA on admission are at risk for subsequent MRSA infection. The reported incidence of infection in MRSA carriers ranges from 24 to 87% (15Singh N Paterson DL Chang FY et al.Methicillin-resistant Staphylococcus aureus: The other emerging resistant Gram-positive coccus among liver transplant recipients.Clin Infect Dis. 2000; 30: 322-327Crossref PubMed Scopus (128) Google Scholar,23Bert F Galdbart JO Zarrouk V et al.Association between nasal carriage of Staphylococcus aureus and infection in liver transplant recipients.Clin Infect Dis. 2000; 31: 1295-1299Crossref PubMed Scopus (67) Google Scholar, 24Desai D Desai N Nightingale P Elliott T Neuberger J Carriage of methicillin-resistant Staphylococcus aureus is associated with an increased risk of infection after liver transplantation.Liver Transpl. 2003; 9: 754-759Crossref PubMed Scopus (70) Google Scholar, 25Russell DL Flood A Zaroda TE et al.Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients.Am J Transplant. 2008; 8: 1737-1743Crossref PubMed Scopus (114) Google Scholar). MRSA carriage among liver transplant recipients does not seem to significantly affect mortality (24Desai D Desai N Nightingale P Elliott T Neuberger J Carriage of methicillin-resistant Staphylococcus aureus is associated with an increased risk of infection after liver transplantation.Liver Transpl. 2003; 9: 754-759Crossref PubMed Scopus (70) Google Scholar,25Russell DL Flood A Zaroda TE et al.Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients.Am J Transplant. 2008; 8: 1737-1743Crossref PubMed Scopus (114) Google Scholar). In contrast, MRSA infection is associated with increased mortality (15Singh N Paterson DL Chang FY et al.Methicillin-resistant Staphylococcus aureus: The other emerging resistant Gram-positive coccus among liver transplant recipients.Clin Infect Dis. 2000; 30: 322-327Crossref PubMed Scopus (128) Google Scholar,25Russell DL Flood A Zaroda TE et al.Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients.Am J Transplant. 2008; 8: 1737-1743Crossref PubMed Scopus (114) Google Scholar). The incidence of MRSA infection seems to be higher in newly colonized patients than in chronic carriers (26Davis KA Stewart JJ Crouch HK Florez CE Hospenthal DR Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection.Clin Infect Dis. 2004; 39: 776-782Crossref PubMed Scopus (495) Google Scholar), although data on transplant recipients are lacking. Donor-derived MRSA infection transmitted from a healthy living donor has been reported (27Obed A Schnitzbauer AA Bein T Lehn N Linde HJ Schlitt HJ Fatal pneumonia caused by Panton–Valentine Leucocidine-positive methicillin-resistant Staphylococcus aureus (PVL-MRSA) transmitted from a healthy donor in living-donor liver transplantation.Transplantation. 2006; 81: 121-124Crossref PubMed Scopus (42) Google Scholar). The increasing incidence of community-associated MRSA (CA-MRSA) is becoming a public health problem of great concern (28David MZ Daum RS Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic.Clin Microbiol Rev. 2010; 23: 616-687Crossref PubMed Scopus (1398) Google Scholar,29Deleo FR Otto M Kreiswirth BN Chambers HF Community-associated meticillin-resistant Staphylococcus aureus.Lancet. 2010; 375: 1557-1568Abstract Full Text Full Text PDF PubMed Scopus (994) Google Scholar). CA-MRSA strains were originally isolated in patients who did not have contact with the healthcare system and were distinguished from healthcare-associated MRSA (HA-MRSA) through epidemiologic and antimicrobial resistance patterns. Most CA-MRSA strains carry staphylococcal chromosome cassette (SCCmec) type IV and genes for the exotoxin Panton-Valentine leukocidin (PVL) (30Moroney SM Heller LC Arbuckle J Talavera M Widen RH Staphylococcal cassette chromosome mec and Panton–Valentine leukocidin characterization of methicillin-resistant Staphylococcus aureus clones.J Clin Microbiol. 2007; 45: 1019-1021Crossref PubMed Scopus (33) Google Scholar). CA-MRSA has a worldwide distribution, but its prevalence varies geographically. In a study conducted in 12 US emergency departments, the prevalence of MRSA was 59% among all skin and soft-tissue infections (SSTIs) and clone USA300 accounted for almost all isolates (31Talan DA Krishnadasan A Gorwitz RJ et al.Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients, 2004 and 2008.Clin Infect Dis. 2011; 53: 144-149Crossref PubMed Scopus (257) Google Scholar). Clone USA300 also causes an increasing proportion of hospital-onset invasive MRSA infections (28David MZ Daum RS Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic.Clin Microbiol Rev. 2010; 23: 616-687Crossref PubMed Scopus (1398) Google Scholar,29Deleo FR Otto M Kreiswirth BN Chambers HF Community-associated meticillin-resistant Staphylococcus aureus.Lancet. 2010; 375: 1557-1568Abstract Full Text Full Text PDF PubMed Scopus (994) Google Scholar,32Klevens RM Morrison MA Nadle J et al.Invasive methicillin-resistant Staphylococcus aureus infections in the United States.JAMA. 2007; 298: 1763-1771Crossref PubMed Scopus (2728) Google Scholar,33Tenover FC Goering RV Methicillin-resistant Staphylococcus aureus strain USA300: origin and epidemiology.J Antimicrob Chemother. 2009; 64: 441-446Crossref PubMed Scopus (334) Google Scholar). CA-MRSA prevalence is lower in Europe and currently the most important risk factor is traveling to or origin from high-prevalence countries (34Denis O Deplano A De Beenhouwer H et al.Polyclonal emergence and importation of community-acquired methicillin-resistant Staphylococcus aureus strains harbouring Panton–Valentine leucocidin genes in Belgium.J Antimicrob Chemother. 2005; 56: 1103-1106Crossref PubMed Scopus (120) Google Scholar,35Larsen AR Stegger M Bocher S Sorum M Monnet DL Skov RL Emergence and characterization of community-associated methicillin-resistant Staphyloccocus aureus infections in Denmark, 1999 to 2006.J Clin Microbiol. 2009; 47: 73-78Crossref PubMed Scopus (86) Google Scholar). Isolated cases and small outbreaks caused by different clones have been documented in many European countries (3Kock R Becker K Cookson B et al.Methicillin-resistant Staphylococcus aureus (MRSA): Burden of disease and control challenges in Europe.Euro Surveill. 2010; 15: 19688Crossref PubMed Scopus (419) Google Scholar,36Johnson AP Methicillin-resistant Staphylococcus aureus: The European landscape.J Antimicrob Chemother. 2011; 66: iv43-iv48Crossref PubMed Scopus (166) Google Scholar). Furthermore, CA-MRSA is spreading from the community into hospitals, and the incidence of CA-MRSA infections and outbreaks in hospitalized patients is increasing (28David MZ Daum RS Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic.Clin Microbiol Rev. 2010; 23: 616-687Crossref PubMed Scopus (1398) Google Scholar,36Johnson AP Methicillin-resistant Staphylococcus aureus: The European landscape.J Antimicrob Chemother. 2011; 66: iv43-iv48Crossref PubMed Scopus (166) Google Scholar,37Navarro MB Huttner B Harbarth S Methicillin-resistant Staphylococcus aureus control in the 21st century: Beyond the acute care hospital.Curr Opin Infect Dis. 2008; 21: 372-379Crossref PubMed Scopus (38) Google Scholar). An increasing prevalence of CA-MRSA colonization in livestock with the potential of human spread has also been reported (3Kock R Becker K Cookson B et al.Methicillin-resistant Staphylococcus aureus (MRSA): Burden of disease and control challenges in Europe.Euro Surveill. 2010; 15: 19688Crossref PubMed Scopus (419) Google Scholar,28David MZ Daum RS Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic.Clin Microbiol Rev. 2010; 23: 616-687Crossref PubMed Scopus (1398) Google Scholar,29Deleo FR Otto M Kreiswirth BN Chambers HF Community-associated meticillin-resistant Staphylococcus aureus.Lancet. 2010; 375: 1557-1568Abstract Full Text Full Text PDF PubMed Scopus (994) Google Scholar,36Johnson AP Methicillin-resistant Staphylococcus aureus: The European landscape.J Antimicrob Chemother. 2011; 66: iv43-iv48Crossref PubMed Scopus (166) Google Scholar). CA-MRSA can be transmitted from person to person. In US studies, the following groups were found to be at risk for colonization or infection: neonates and children; athletes who participate in contact sports; injection drug users; men who have sex with men; military personnel; persons living in correctional facilities, nursing homes, or shelters; adults 65 years or older; veterinarians; pet owners; pig and horse farmers. HIV infection, cystic fibrosis and household contact with a person known to be colonized or infected with MRSA are additional risk factors. The presence of SSTI or a history of recent severe pneumonia should raise the suspicion of CA-MRSA colonization (28David MZ Daum RS Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic.Clin Microbiol Rev. 2010; 23: 616-687Crossref PubMed Scopus (1398) Google Scholar,38Boucher HW Corey GR Epidemiology of methicillin-resistant Staphylococcus aureus.Clin Infect Dis. 2008; 46: S344-S349Crossref PubMed Scopus (616) Google Scholar). In the general population, CA-MRSA is typically associated with uncomplicated SSTIs but can also cause severe disease, such as necrotizing fasciitis or necrotizing pneumonia (28David MZ Daum RS Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic.Clin Microbiol Rev. 2010; 23: 616-687Crossref PubMed Scopus (1398) Google Scholar,29Deleo FR Otto M Kreiswirth BN Chambers HF Community-associated meticillin-resistant Staphylococcus aureus.Lancet. 2010; 375: 1557-1568Abstract Full Text Full Text PDF PubMed Scopus (994) Google Scholar,38Boucher HW Corey GR Epidemiology of methicillin-resistant Staphylococcus aureus.Clin Infect Dis. 2008; 46: S344-S349Crossref PubMed Scopus (616) Google Scholar). Certain strains, notably USA300, often produce PVL, whose role in the virulence of MRSA remains controversial. Infection with CA-MRSA has been reported among transplant patients; very few epidemiologic data exist (27Obed A Schnitzbauer AA Bein T Lehn N Linde HJ Schlitt HJ Fatal pneumonia caused by Panton–Valentine Leucocidine-positive methicillin-resistant Staphylococcus aureus (PVL-MRSA) transmitted from a healthy donor in living-donor liver transplantation.Transplantation. 2006; 81: 121-124Crossref PubMed Scopus (42) Google Scholar,39Adeyemi OA Qi C Zembower TR et al.Invasive infections with community-associated methicillin-resistant Staphylococcus aureus after kidney transplantation.J Clin Microbiol. 2008; 46: 2809-2813Crossref Scopus (10) Google Scholar) but possibly follow the trends of the general population. In a single-center study from Canada, among 17 cases of MRSA colonization and/or infection, all strains were found to be hospital-associated (13Manuel O Lien D Weinkauf J Humar A Cobos I Kumar D Methicillin-resistant Staphylococcus aureus infection after lung transplantation: 5-year review of clinical and molecular epidemiology.J Heart Lung Transplant. 2009; 28: 1231-1236Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar). Considering the increasing incidence, infection with CA-MRSA should be suspected even in low-prevalence areas. The prevalence of vancomycin-intermediate S. aureus (VISA) and heteroresistant VISA (hVISA) is increasing worldwide with major regional differences (40Howden BP Davies JK Johnson PD Stinear TP Grayson ML Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: Resistance mechanisms, laboratory detection, and clinical implications.Clin Microbiol Rev. 2010; 23: 99-139Crossref PubMed Scopus (690) Google Scholar,41Richter SS Satola SW Crispell EK et al.Detection of Staphylococcus aureus isolates with heterogeneous intermediate-level resistance to vancomycin in the United States.J Clin Microbiol. 2011; 49: 4203-4207Crossref PubMed Scopus (51) Google Scholar). Lacking a standardized detection method, findings on prevalence depend on study methodology. Data on transplant recipients are sparse. In a French study, heterogeneous glyocopeptide intermediate S. aureus strains were found in 13 (27%) of 48 patients (42Bert F Clarissou J Durand F et al.Prevalence, molecular epidemiology, and clinical significance of heterogeneous glycopeptide-intermediate Staphylococcus aureus in liver transplant recipients.J Clin Microbiol. 2003; 41: 5147-5152Crossref PubMed Scopus (36) Google Scholar). Vancomycin-resistant S. aureus (VRSA) has been shown to occur through transfer of the vanA gene from vancomycin-resistant enterococci (VRE) to MRSA. Few cases of VRSA have been reported to date in the United States (43Sievert DM Rudrik JT Patel JB McDonald LC Wilkins MJ Hageman JC Vancomycin-resistant Staphylococcus aureus in the United States, 2002–2006.Clin Infect Dis. 2008; 46: 668-674Crossref PubMed Scopus (411) Google Scholar) and Asia (44Saha B Singh AK Ghosh A Bal M Identification and characterization of a vancomycin-resistant Staphylococcus aureus isolated from Kolkata (South Asia).J Med Microbiol. 2008; 57: 72-79Crossref Scopus (148) Google Scholar,45Aligholi M Emaneini M Jabalameli F Shahsavan S Dabiri H Sedaght H Emergence of high-level vancomycin-resistant Staphylococcus aureus in the Imam Khomeini Hospital in Tehran.Med Princ Pract. 2008; 17: 432-434Crossref PubMed Scopus (95) Google Scholar); none among transplant recipients. Factors that have been associated with VRSA infection are colonization or infection with MRSA or VRE, prior use of vancomycin, presence of chronic cutaneous ulcers and diabetes mellitus (43Sievert DM Rudrik JT Patel JB McDonald LC Wilkins MJ Hageman JC Vancomycin-resistant Staphylococcus aureus in the United States, 2002–2006.Clin Infect Dis. 2008; 46: 668-674Crossref PubMed Scopus (411) Google Scholar). Transplant recipients have multiple comorbidities and are potentially at risk for VRSA infection. S. aureus infections occurring in the first 3 posttransplant months are typically related to the surgical procedure and use of medical devices such as intravenous catheters and endotracheal tubes (7Bert F Larroque B Paugam-Burtz C et al.Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients: An analysis of 259 episodes.Liver Transpl. 2010; 16: 393-401Crossref PubMed Scopus (93) Google Scholar,9Malinis MF Mawhorter SD Jain A Shrestha NK Avery RK van Duin D Staphylococcus aureus bacteremia in solid organ transplant recipients: Evidence for improved survival when compared with nontransplant patients.Transplantation. 2012; 93: 1045-1050Crossref PubMed Scopus (36) Google Scholar,10Singh N Wagener MM Obman A Cacciarelli TV de Vera ME Gayowski T Bacteremias in liver transplant recipients: Shift toward gram-negative bacteria as predominant pathogens.Liver Transpl. 2004; 10: 844-849Crossref PubMed Scopus (142) Google Scholar,46Fishman JA Infection in solid-organ transplant recipients.N Engl J Med. 2007; 357: 2601-2614Crossref PubMed Scopus (1382) Google Scholar). MRSA most commonly causes bloodstream, lower respiratory tract, wound and intraabdominal infections. Diagnosis is established by isolation of the organism from affected sites. In general, isolation of S. aureus from a normally sterile body site or blood culture is diagnostic of infection. Depending on the clinical context, MRSA isolated in sputum, wound culture or fluid obtained from a drainage catheter may represent infection or mere colonization. In the absence of consistent clinical symptoms, signs and/or radiographic findings, isolation of the pathogen is more likely to represent colonization than infection and antibiotic treatment is not required. Detection of Gram-positive cocci in clusters on Gram stain of the direct specimen provides an early clue to diagnosis. Rapid diagnostic assays, such as real-time PCR (47Wellinghausen N Siegel D Gebert S Winter J Rapid detection of Staphylococcus aureus bacteremia and methicillin resistance by real-time PCR in whole blood samples.Eur J Clin Microbiol Infect Dis. 2009; 28: 1001-1005Crossref PubMed Scopus (25) Google Scholar), fluorescent in situ hybridization employing peptide nucleic acid probes (PNA-FISH) (48Gonzalez V Padilla E Gimenez M et al.Rapid diagnosis of Staphylococcus aureus bacteremia using S. aureus PNA FISH.Eur J Clin Microbiol Infect Dis. 2004; 23: 396-398Crossref PubMed Scopus (47) Google Scholar) and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF) (49Lagace-Wiens PR Adam HJ Karlowsky JA et al.Identification of blood culture isolates directly from positive blood cultures using MALDI-TOF mass spectrometry and a commercial extraction system—analysis of performance, cost and turnaround time.J Clin Microbiol. 2012; 50: 3324-3328Crossref PubMed Scopus (153) Google Scholar) can expedite the characterization of Gram-positive cocci in blood cultures. For infection control purposes, surveillance cultures may be obtained from the anterior nares, throat, axillae, rectum or open wound areas. Traditional culture techniques provide results within 24–72 h. Chromogenic agar can be used to detect MRSA with a very high negative predictive value after only 24 h of incubation. A longer incubation period of 48 h slightly increases the sensitivity of the assay (50Carson J Lui B Rosmus L Rennick H Fuller J Interpretation of MRSASelect screening agar at 24 hours of incubation.J Clin Microbiol. 2009; 47: 566-568Crossref Scopus (25) Google Scholar). Molecular techniques targeting DNA sequences within SCCmec, a mobile element carrying the methicillin-resistance gene mecA, allow for MRSA detection within 2–6 h (51Warren DK Liao RS Merz LR Eveland M Dunne Jr, WM Detection of methicillin-resistant Staphylococcus aureus directly from nasal swab specimens by a real-time PCR assay.J Clin Microbiol. 2004; 42: 5578-5581Crossref PubMed Scopus (182) Google Scholar). Isolates with oxacillin MIC ≥4 μg/mL or methicillin MIC ≥16 μg/mL are considered methicillin-resistant. A 30 μg cefoxitin disk is more sensitive in detecting methicillin resistance than a 1 μg oxacillin disk (52Broekema NM Van TT Monson TA Marshall SA Warshauer DM Comparison of cefoxitin and oxacillin disk diffusion methods for detection of mecA-mediated resistance in Staphylococcus aureus in a large-scale study.J Clin Microbiol. 2009; 47: 217-219Crossref PubMed Scopus (74) Google Scholar). Molecular methods can be used to detect the mecA gene which codes for penicillin binding protein 2a and has been associated with resistance to beta lactams. In 2006, the Clinical and Laboratory Standards Institute (CLSI) lowered the vancomycin breakpoints for MRSA. Current breakpoints are ≤2 μg/mL for susceptible, 4–8 μg/mL for intermediate and ≥16 μg/mL for resistant isolates (53CLSIMethods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—8th Ed. CLSI document M07-A8, Vol. 29 No 2.. Clinical and Laboratory Standards Institute, Wayne, PA2009Google Scholar). Vancomycin has been considered the drug of choice for MRSA infections (I). However, strains with reduced susceptibility have emerged. VISA strains are homogeneous bacterial populations with MIC of 4–8 μg/mL. hVISA strains are susceptible using standard broth microdilution, but contain a small subpopulation of bacteria (1/105–106) that show intermediate susceptibility to vancomycin. VISA and hVISA strains are difficult to detect with automated standard MIC methodology and disk diffusion testing. E-test can improve the detection of VISA. Routine use of alternative methods for hVISA detection is not routinely recommended. Clinicians and microbiology laboratory personnel should be aware of this pitfall, as those strains have been associated with treatment failures (54Holmes NE Johnson PD Howden BP The relationship between hVISA, VISA, high vancomycin MIC and outcome in serious Staphylococcus aureus infection.J Clin Microbiol. 2012; 50: 2548-2552Crossref PubMed Scopus (74) Google Scholar). For an insufficient or failed response to vancomycin, particularly with strains at the upper end of the susceptible range (2 μg/mL), hVISA and VISA should be suspected. This should be communicated to the microbiology laboratory. If necessary, the strain can be further tested at a reference laboratory. A more detailed review is beyond the scope of this text; please refer to IDSA Guidelines (55Liu C Bayer A Cosgrove SE et al.Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: Executive summary.Clin Infect Dis. 2011; 52: 285-292Crossref PubMed Scopus (1282) Google Scholar),
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