Use of rapid diagnostic techniques in ICU patients with infections

BMC Infectious Diseases

Emilio Bouza²  Almudena Burillo¹ 

[1] Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain;CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain

关键词: Microbiology;    Intensive care unit;    Clinical laboratory techniques;    Rapid diagnosis;   

Others  :  1118316
DOI  :  10.1186/s12879-014-0593-1

 received in 2014-04-08, accepted in 2014-10-28,  发布年份 2014

【 摘 要 】

Background

Infection is a common complication seen in ICU patients. Given the correlation between infection and mortality in these patients, a rapid etiological diagnosis and the determination of antimicrobial resistance markers are of paramount importance, especially in view of today’s globally spread of multi drug resistance microorganisms. This paper reviews some of the rapid diagnostic techniques available for ICU patients with infections.

Methods

A narrative review of recent peer-reviewed literature (published between 1995 and 2014) was performed using as the search terms: Intensive care medicine, Microbiological techniques, Clinical laboratory techniques, Diagnosis, and Rapid diagnosis, with no language restrictions.

Results

The most developed microbiology fields for a rapid diagnosis of infection in critically ill patients are those related to the diagnosis of bloodstream infection, pneumonia –both ventilator associated and non-ventilator associated–, urinary tract infection, skin and soft tissue infections, viral infections and tuberculosis.

Conclusions

New developments in the field of microbiology have served to shorten turnaround times and optimize the treatment of many types of infection. Although there are still some unresolved limitations of the use of molecular techniques for a rapid diagnosis of infection in the ICU patient, this approach holds much promise for the future.

【 授权许可】

   
2014 Burillo and Bouza; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Burgmann H, Hiesmayr JM, Savey A, Bauer P, Metnitz B, Metnitz PG: Impact of nosocomial infections on clinical outcome and resource consumption in critically ill patients. Intensive Care Med 2010, 36:1597-1601.
• [2]Cohen ER, Feinglass J, Barsuk JH, Barnard C, O’Donnell A, McGaghie WC, Wayne DB: Cost savings from reduced catheter-related bloodstream infection after simulation-based education for residents in a medical intensive care unit. Simul Healthc 2010, 5:98-102.
• [3]Zarb P, Coignard B, Griskeviciene J, Muller A, Vankerckhoven V, Weist K, Goossens M, Vaerenberg S, Hopkins S, Catry B, Monnet D, Goossens H, Suetens C: The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use. Euro Surveill 2012, 17:20316.
• [4]Olaechea PM, Palomar M, Alvarez-Lerma F, Otal JJ, Insausti J, Lopez-Pueyo MJ: Morbidity and mortality associated with primary and catheter-related bloodstream infections in critically ill patients. Rev Esp Quimioter 2013, 26:21-29.
• [5]Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK: 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, 29:996-1011.
• [6]Brusselaers N, Vogelaers D, Blot S: The rising problem of antimicrobial resistance in the intensive care unit. Ann Intensive Care 2011, 1:47.
• [7]Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH: The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000, 118:146-155.
• [8]Muscedere JG, Shorr AF, Jiang X, Day A, Heyland DK: The adequacy of timely empiric antibiotic therapy for ventilator-associated pneumonia: an important determinant of outcome. J Crit Care 2012, 27:322. e327-314
• [9]Palmer HR, Palavecino EL, Johnson JW, Ohl CA, Williamson JC: Clinical and microbiological implications of time-to-positivity of blood cultures in patients with Gram-negative bacilli bacteremia. Eur J Clin Microbiol Infect Dis 2013, 32:955-959.
• [10]Raad I, Hanna H, Maki D: Intravascular catheter-related infections: advances in diagnosis, prevention, and management. Lancet Infect Dis 2007, 7:645-657.
• [11]Rello J, Coll P, Prats G: Evaluation of culture techniques for diagnosis of catheter-related sepsis in critically ill patients. Eur J Clin Microbiol Infect Dis 1992, 11:1192-1193.
• [12]Benezra D, Kiehn TE, Gold JW, Brown AE, Turnbull AD, Armstrong D: Prospective study of infections in indwelling central venous catheters using quantitative blood cultures. Am J Med 1988, 85:495-498.
• [13]Rijnders BJ, Peetermans WE, Verwaest C, Wilmer A, Van Wijngaerden E: Watchful waiting versus immediate catheter removal in ICU patients with suspected catheter-related infection: a randomized trial. Intensive Care Med 2004, 30:1073-1080.
• [14]Fortun J, Grill F, Martin-Davila P, Blazquez J, Tato M, Sanchez-Corral J, Garcia-San Miguel L, Moreno S: Treatment of long-term intravascular catheter-related bacteraemia with antibiotic-lock therapy. J Antimicrob Chemother 2006, 58:816-821.
• [15]Safdar N, Fine JP, Maki DG: Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection. Ann Intern Med 2005, 142:451-466.
• [16]Cercenado E, Ena J, Rodriguez-Creixems M, Romero I, Bouza E: A conservative procedure for the diagnosis of catheter-related infections. Arch Intern Med 1990, 150:1417-1420.
• [17]Fortun J, Perez-Molina JA, Asensio A, Calderon C, Casado JL, Mir N, Moreno A, Guerrero A: Semiquantitative culture of subcutaneous segment for conservative diagnosis of intravascular catheter-related infection. JPEN J Parenter Enteral Nutr 2000, 24:210-214.
• [18]Bouza E, Munoz P, Burillo A, Lopez-Rodriguez J, Fernandez-Perez C, Perez MJ, Rincon C: The challenge of anticipating catheter tip colonization in major heart surgery patients in the intensive care unit: are surface cultures useful? Crit Care Med 2005, 33:1953-1960.
• [19]Blot F: Diagnosis of catheter-related infections. In Catheter-Related Infections. Edited by Seifert H, Jansen B, Farr B. Marcel Dekker, New York; 2005:37-76.
• [20]Guembe M, Rodriguez-Creixems M, Sanchez-Carrillo C, Perez-Parra A, Martin-Rabadan P, Bouza E: How many lumens should be cultured in the conservative diagnosis of catheter-related bloodstream infections? Clin Infect Dis 2010, 50:1575-1579.
• [21]Hamilton DJ, Amos D, Schwartz RW, Dent CM, Counts GW: Effect of delay in processing on lysis-centrifugation blood culture results from marrow transplant patients. J Clin Microbiol 1989, 27:1588-1593.
• [22]Raad I, Hanna HA, Alakech B, Chatzinikolaou I, Johnson MM, Tarrand J: Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections. Ann Intern Med 2004, 140:18-25.
• [23]Sabatier C, Garcia X, Ferrer R, Duarte M, Colomina M, Alcaraz D, Fontanals D, Valles J: Blood culture differential time to positivity enables safe catheter retention in suspected catheter-related bloodstream infection: a randomized controlled trial.Med Intensiva 2014, in press.
• [24]Blot F, Nitenberg G, Chachaty E, Raynard B, Germann N, Antoun S, Laplanche A, Brun-Buisson C, Tancrede C: Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet 1999, 354:1071-1077.
• [25]Abdelkefi A, Achour W, Ben Othman T, Torjman L, Ladeb S, Lakhal A, Hsairi M, Kammoun L, Ben Hassen A, Ben Abdeladhim A: Difference in time to positivity is useful for the diagnosis of catheter-related bloodstream infection in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2005, 35:397-401.
• [26]Kaasch AJ, Rieg S, Hellmich M, Kern WV, Seifert H: Differential time to positivity is not predictive for central line-related Staphylococcus aureus bloodstream infection in routine clinical care. J Infect 2014, 68:58-61.
• [27]Schwetz I, Hinrichs G, Reisinger EC, Krejs GJ, Olschewski H, Krause R: Delayed processing of blood samples influences time to positivity of blood cultures and results of Gram stain-acridine orange leukocyte Cytospin test. J Clin Microbiol 2007, 45:2691-2694.
• [28]Kaasch AJ, Rieg S, Hellmich M, Kern WV, Seifert H: Reply to Krause et al. J Infect 2014, 69:294-295.
• [29]Bouza E, Alcala L, Munoz P, Martin-Rabadan P, Guembe M, Rodriguez-Creixems M: Can microbiologists help to assess catheter involvement in candidaemic patients before removal? Clin Microbiol Infect 2013, 19:E129-E135.
• [30]Leon M, Garcia M, Herranz MA, Gonzalez V, Martinez A, Castillo F, Andres E, Leon C, Huet J: Diagnostic value of Gram staining of peri-catheter skin and the connection in the prediction of intravascular-catheter-related bacteremia. Enferm Infecc Microbiol Clin 1998, 16:214-218.
• [31]Bouza E, Alvarado N, Alcala L, Perez MJ, Rincon C, Munoz P: A randomized and prospective study of 3 procedures for the diagnosis of catheter-related bloodstream infection without catheter withdrawal. Clin Infect Dis 2007, 44:820-826.
• [32]Castellanos-Ortega A, Suberviola B, Garcia-Astudillo LA, Holanda MS, Ortiz F, Llorca J, Delgado-Rodriguez M: Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study. Crit Care Med 2010, 38:1036-1043.
• [33]Fenollar F, Raoult D: Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria. Int J Antimicrob Agents 2007, 30(Suppl 1):S7-S15.
• [34]Afshari A, Schrenzel J, Ieven M, Harbarth S: Bench-to-bedside review: rapid molecular diagnostics for bloodstream infection - a new frontier? Crit Care 2012, 16:222.
• [35]Liesenfeld O, Lehman L, Hunfeld KP, Kost G: Molecular diagnosis of sepsis: New aspects and recent developments. Eur J Microbiol Immunol (Bp) 2014, 4:1-25.
• [36]Murray PR, Masur H: Current approaches to the diagnosis of bacterial and fungal bloodstream infections in the intensive care unit. Crit Care Med 2012, 40:3277-3282.
• [37]Chang SS, Hsieh WH, Liu TS, Lee SH, Wang CH, Chou HC, Yeo YH, Tseng CP, Lee CC: Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis - a systemic review and meta-analysis. PLoS One 2013, 8:e62323.
• [38]Wallet F, Loiez C, Herwegh S, Courcol RJ: Usefulness of real-time PCR for the diagnosis of sepsis in ICU-acquired infections. Infect Disord Drug Targets 2011, 11:348-353.
• [39]Schrenzel J: PCR for the diagnosis of sepsis: hope or hype? Crit Care 2011, 15:111.
• [40]Dierkes C, Ehrenstein B, Siebig S, Linde HJ, Reischl U, Salzberger B: Clinical impact of a commercially available multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis. BMC Infect Dis 2009, 9:126.
• [41]Fernandez-Cruz A, Marin M, Kestler M, Alcala L, Rodriguez-Creixems M, Bouza E: The value of combining blood culture and SeptiFast data for predicting complicated bloodstream infections caused by Gram-positive bacteria or Candida species. J Clin Microbiol 2013, 51:1130-1136.
• [42]Lehmann LE, Herpichboehm B, Kost GJ, Kollef MH, Stuber F: Cost and mortality prediction using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials. Crit Care 2010, 14:R186.
• [43]Ho YP, Reddy PM: Advances in mass spectrometry for the identification of pathogens. Mass Spectrom Rev 2011, 30:1203-1224.
• [44]Cherkaoui A, Hibbs J, Emonet S, Tangomo M, Girard M, Francois P, Schrenzel J: Comparison of two matrix-assisted laser desorption ionization-time of flight mass spectrometry methods with conventional phenotypic identification for routine identification of bacteria to the species level. J Clin Microbiol 2010, 48:1169-1175.
• [45]Spanu T, Posteraro B, Fiori B, D’Inzeo T, Campoli S, Ruggeri A, Tumbarello M, Canu G, Trecarichi EM, Parisi G, Tronci M, Sanguinetti M, Fadda G: Direct maldi-tof mass spectrometry assay of blood culture broths for rapid identification of Candida species causing bloodstream infections: an observational study in two large microbiology laboratories. J Clin Microbiol 2012, 50:176-179.
• [46]Juiz PM, Almela M, Melcion C, Campo I, Esteban C, Pitart C, Marco F, Vila J: A comparative study of two different methods of sample preparation for positive blood cultures for the rapid identification of bacteria using MALDI-TOF MS. Eur J Clin Microbiol Infect Dis 2012, 31:1353-1358.
• [47]Leli C, Cenci E, Cardaccia A, Moretti A, D’Alo F, Pagliochini R, Barcaccia M, Farinelli S, Vento S, Bistoni F, Mencacci A: Rapid identification of bacterial and fungal pathogens from positive blood cultures by MALDI-TOF MS. Int J Med Microbiol 2013, 303:205-209.
• [48]Rodriguez-Sanchez B, Sanchez-Carrillo C, Ruiz A, Marin M, Cercenado E, Rodriguez-Creixems M, Bouza E: Direct identification of pathogens from positive blood cultures using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Clin Microbiol Infec 2013.
• [49]Vlek AL, Bonten MJ, Boel CH: Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry improves appropriateness of antibiotic treatment of bacteremia. PLoS One 2012, 7:e32589.
• [50]Reinhart K, Bauer M, Riedemann NC, Hartog CS: New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 2012, 25:609-634.
• [51]Pierrakos C, Vincent JL: Sepsis biomarkers: a review. Crit Care 2010, 14:R15.
• [52]Povoa P, Coelho L, Almeida E, Fernandes A, Mealha R, Moreira P, Sabino H: C-reactive protein as a marker of infection in critically ill patients. Clin Microbiol Infect 2005, 11:101-108.
• [53]Povoa P, Coelho L, Almeida E, Fernandes A, Mealha R, Moreira P, Sabino H: Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study. Crit Care 2006, 10:R63.
• [54]Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL: C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003, 123:2043-2049.
• [55]Garnacho-Montero J, Huici-Moreno MJ, Gutierrez-Pizarraya A, Lopez I, Marquez-Vacaro JA, Macher H, Guerrero JM, Puppo-Moreno A: Prognostic and diagnostic value of eosinopenia, C-reactive protein, procalcitonin, and circulating cell-free DNA in critically ill patients admitted with suspicion of sepsis. Crit Care 2014, 18:R116.
• [56]Giamarellos-Bourboulis EJ, Tsangaris I, Kanni T, Mouktaroudi M, Pantelidou I, Adamis G, Atmatzidis S, Chrisofos M, Evangelopoulou V, Frantzeskaki F, Giannopoulos P, Giannikopoulos G, Gialvalis D, Gourgoulis GM, Kotzampassi K, Katsifa K, Kofinas G, Kontopidou F, Koratzanis G, Koulouras V, Koutsikou A, Koupetori M, Kritselis I, Leonidou L, Mega A, Mylona V, Nikolaou H, Orfanos S, Panagopoulos P, Paramythiotou E, et al.: Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study. J Hosp Infect 2011, 77:58-63.
• [57]Karlsson S, Heikkinen M, Pettila V, Alila S, Vaisanen S, Pulkki K, Kolho E, Ruokonen E: Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study. Crit Care 2010, 14:R205.
• [58]Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013, 41:580-637.
• [59]Rello J: Bench-to-bedside review: Therapeutic options and issues in the management of ventilator-associated bacterial pneumonia. Crit Care 2005, 9:259-265.
• [60]Kollef MH: What is ventilator-associated pneumonia and why is it important? Respir Care 2005, 50:714-724.
• [61]Chastre J: Conference summary: ventilator-associated pneumonia. Respir Care 2005, 50:975-983.
• [62]Muscedere JG, Martin CM, Heyland DK: The impact of ventilator-associated pneumonia on the Canadian health care system. J Crit Care 2008, 23:5-10.
• [63]Hortal J, Munoz P, Cuerpo G, Litvan H, Rosseel PM, Bouza E: Ventilator-associated pneumonia in patients undergoing major heart surgery: an incidence study in Europe. Crit Care 2009, 13:R80.
• [64]Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH: Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002, 122:262-268.
• [65]Kuti EL, Patel AA, Coleman CI: Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associated pneumonia and blood stream infection: a meta-analysis. J Crit Care 2008, 23:91-100.
• [66]Blot S: Limiting the attributable mortality of nosocomial infection and multidrug resistance in intensive care units. Clin Microbiol Infect 2008, 14(1):5-13.
• [67]Bogaerts P, Hamels S, de Mendonca R, Huang TD, Roisin S, Remacle J, Markine-Goriaynoff N, de Longueville F, Pluster W, Denis O, Glupczynski Y: Analytical validation of a novel high multiplexing real-time PCR array for the identification of key pathogens causative of bacterial ventilator-associated pneumonia and their associated resistance genes. J Antimicrob Chemother 2013, 68:340-347.
• [68]Hogardt M, Trebesius K, Geiger AM, Hornef M, Rosenecker J, Heesemann J: Specific and rapid detection by fluorescent in situ hybridization of bacteria in clinical samples obtained from cystic fibrosis patients. J Clin Microbiol 2000, 38:818-825.
• [69]Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia Am J Respir Crit Care Med 2005, 171:388-416.
• [70]de Jaeger A, Litalien C, Lacroix J, Guertin MC, Infante-Rivard C: Protected specimen brush or bronchoalveolar lavage to diagnose bacterial nosocomial pneumonia in ventilated adults: a meta-analysis. Crit Care Med 1999, 27:2548-2560.
• [71]Torres A, El-Ebiary M: Bronchoscopic BAL in the diagnosis of ventilator-associated pneumonia. Chest 2000, 117(4 Suppl 2):198S-202S.
• [72]Berton DC, Kalil AC, Teixeira PJZ: Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia.Cochrane Database of Systematic Reviews 2014, ᅟ(10):CD006482. DOI:10.1002/14651858.CD006482.pub4.
• [73]Baselski VS, El-Torky M, Coalson JJ, Griffin JP: The standardization of criteria for processing and interpreting laboratory specimens in patients with suspected ventilator- associated pneumonia. Chest 1992, 102(5 Suppl 1):571S-579S.
• [74]Wunderink RG: Surrogate markers and microbiologic end points. Clin Infect Dis 2010, 51(Suppl 1):S126-S130.
• [75]Georges H, Santre C, Leroy O, Roussel-Delvallez M, Caillaux M, Beuscart C, Guery B, Vandenbussche C, Beaucaire G: Reliability of quantitative cultures of protected specimen brush after freezing. Am J Respir Crit Care Med 1996, 153:855-857.
• [76]de Lassence A, Joly-Guillou ML, Martin-Lefevre L, Le Miere E, Lasry S, Morelot C, Coste F, Dreyfuss D: Accuracy of delayed cultures of plugged telescoping catheter samples for diagnosing bacterial pneumonia. Crit Care Med 2001, 29:1311-1317.
• [77]de Lassence A, Joly-Guillou ML, Salah A, Martin-Lefevre L, Hidri N, Ricard JD, Bouvry D, de Castro N, Dreyfuss D: Accuracy of delayed (24 hours) processing of bronchoalveolar lavage for diagnosing bacterial pneumonia. Crit Care Med 2004, 32:680-685.
• [78]Maillet JM, Fitoussi F, Penaud D, Dennewald G, Brodaty D: Concordance of antibiotic prophylaxis, direct Gram staining and protected brush specimen culture results for postoperative patients with suspected pneumonia. Eur J Anaesthesiol 2006, 23:563-567.
• [79]Davis KA, Eckert MJ, Reed RL 2nd, Esposito TJ, Santaniello JM, Poulakidas S, Luchette FA: Ventilator-associated pneumonia in injured patients: do you trust your Gram’s stain? J Trauma 2005, 58:462-466.
• [80]Blot F, Raynard B, Chachaty E, Tancrede C, Antoun S, Nitenberg G: Value of gram stain examination of lower respiratory tract secretions for early diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med 2000, 162:1731-1737.
• [81]Croce MA, Fabian TC, Waddle-Smith L, Melton SM, Minard G, Kudsk KA, Pritchard FE: Utility of Gram’s stain and efficacy of quantitative cultures for posttraumatic pneumonia: a prospective study. Ann Surg 1998, 227:743-751.
• [82]Prekates A, Nanas S, Argyropoulou A, Margariti G, Kyprianou T, Papagalos E, Paniara O, Roussos C: The diagnostic value of gram stain of bronchoalveolar lavage samples in patients with suspected ventilator-associated pneumonia. Scand J Infect Dis 1998, 30:43-47.
• [83]Marquette CH, Wallet F, Neviere R, Copin MC, Saulnier F, Drault JN, Mehdaoui H, Mathieu D, Ramon P: Diagnostic value of direct examination of the protected specimen brush in ventilator-associated pneumonia. Eur Respir J 1994, 7:105-113.
• [84]dos Santos RP, Deutschendorf C, Nagel F, Konkewicz L, Lisboa T: Antimicrobial stewardship lessons: know when to say no to vancomycin. Clin Infect Dis 2013, 56:616-617.
• [85]Torres M, Radice C, Sánchez C, Martín-Rabadán P, Muñoz P, Bouza E: [Performance of Gram stain in lower respiratory tract (LRT) samples in ventilator-associated pneumonia (VAP): a prospective study]. (Abstract). In: XII Congress of the Spanish Society of Infectious Diseases and Clinical Microbiology. Valencia, Spain; 2006.
• [86]Sirvent JM, Vidaur L, Gonzalez S, Castro P, de Batlle J, Castro A, Bonet A: Microscopic examination of intracellular organisms in protected bronchoalveolar mini-lavage fluid for the diagnosis of ventilator-associated pneumonia. Chest 2003, 123:518-523.
• [87]Timsit JF, Cheval C, Gachot B, Bruneel F, Wolff M, Carlet J, Regnier B: Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia. Intensive Care Med 2001, 27:640-647.
• [88]Mentec H, May-Michelangeli L, Rabbat A, Varon E, Le Turdu F, Bleichner G: Blind and bronchoscopic sampling methods in suspected ventilator-associated pneumonia. A multicentre prospective study. Intensive Care Med 2004, 30:1319-1326.
• [89]Masterton RG, Galloway A, French G, Street M, Armstrong J, Brown E, Cleverley J, Dilworth P, Fry C, Gascoigne AD, Knox A, Nathwani D, Spencer R, Wilcox M: Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2008, 62:5-34.
• [90]Linssen CF, Jacobs JA, Schouten JS, van Mook WN, Ramsay G, Drent M: Influence of antibiotic therapy on the cytological diagnosis of ventilator-associated pneumonia. Intensive Care Med 2008, 34:865-872.
• [91]Rello J, Chastre J, Cornaglia G, Masterton R: A European care bundle for management of ventilator-associated pneumonia. J Crit Care 2011, 26:3-10.
• [92]Coffin SE, Klompas M, Classen D, Arias KM, Podgorny K, Anderson DJ, Burstin H, Calfee DP, Dubberke ER, Fraser V, Gerding DN, Griffin FA, Gross P, Kaye KS, Lo E, Marschall J, Mermel LA, Nicolle L, Pegues DA, Perl TM, Saint S, Salgado CD, Weinstein RA, Wise R, Yokoe DS: Strategies to prevent ventilator-associated pneumonia in acute care hospitals. Infect Control Hosp Epidemiol 2008, 29(Suppl 1):S31-S40.
• [93]Vidaur L, Planas K, Sierra R, Dimopoulos G, Ramirez A, Lisboa T, Rello J: Ventilator-associated pneumonia: impact of organisms on clinical resolution and medical resources utilization. Chest 2008, 133:625-632.
• [94]Bahrani-Mougeot FK, Paster BJ, Coleman S, Barbuto S, Brennan MT, Noll J, Kennedy T, Fox PC, Lockhart PB: Molecular analysis of oral and respiratory bacterial species associated with ventilator-associated pneumonia. J Clin Microbiol 2007, 45:1588-1593.
• [95]Cercenado E, Marin M, Burillo A, Martin-Rabadan P, Rivera M, Bouza E: Rapid detection of Staphylococcus aureus in lower respiratory tract secretions from patients with suspected ventilator-associated pneumonia: evaluation of the Cepheid Xpert MRSA/SA SSTI assay. J Clin Microbiol 2012, 50:4095-4097.
• [96]Leone M, Malavieille F, Papazian L, Meyssignac B, Cassir N, Textoris J, Antonini F, La Scola B, Martin C, Allaouchiche B, Hraiech S: Routine use of Staphylococcus aureus rapid diagnostic test in patients with suspected ventilator-associated pneumonia. Crit Care 2013, 17:R170.
• [97]Oh AC, Lee JK, Lee HN, Hong YJ, Chang YH, Hong SI, Kim DH: Clinical utility of the Xpert MRSA assay for early detection of methicillin-resistant Staphylococcus aureus. Mol Med Rep 2013, 7:11-15.
• [98]Tenover FC: Developing molecular amplification methods for rapid diagnosis of respiratory tract infections caused by bacterial pathogens. Clin Infect Dis 2011, 52(Suppl 4):S338-S345.
• [99]Bolmström A, Arvidson S, Ericsson M, Karlsson A: A novel technique for direct quantification of antimicrobial susceptibility of microorganisms. In 28th Interscience Conference on Antimicrobial Agents and Chemotherapy; Los Angeles, (US); 1988.
• [100]Cercenado E, Rico MV, Vicente T, Bouza E: Rapid Antimicrobial Susceptibility Testing in Patients with Ventilator-Associated Pneumonia: Direct E-Test on Respiratory Samples. (Abstract: D-51). In 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy: 2002; San Diego (US); 2002.
• [101]Bouza E, Torres MV, Radice C, Cercenado E, de Diego R, Sanchez-Carrillo C, Munoz P: Direct E-test (AB Biodisk) of respiratory samples improves antimicrobial use in ventilator-associated pneumonia. Clin Infect Dis 2007, 44(3):382-387.
• [102]Muñoz P, Cercenado E, Giannella M, Bouza E: Rapid detection of microorganism resistance in patients with ventilator-associated pneumonia. Clin Pulm Med 2009, 16(6):302-308.
• [103]Cercenado E, Marin M, Insa R, Martin-Rabadan P, Rivera M, Bouza E: Evaluation of direct E-test on lower respiratory tract samples using a chromogenic agar medium: a rapid procedure for antimicrobial susceptibility testing. (Abstract P822). In 19th Congress of the ESCMID: 2009. Helsinki, Finland; 2009.
• [104]Lisboa T, Seligman R, Diaz E, Rodriguez A, Teixeira PJ, Rello J: C-reactive protein correlates with bacterial load and appropriate antibiotic therapy in suspected ventilator-associated pneumonia. Crit Care Med 2008, 36:166-171.
• [105]Jung B, Embriaco N, Roux F, Forel JM, Demory D, Allardet-Servent J, Jaber S, La Scola B, Papazian L: Microbiogical data, but not procalcitonin improve the accuracy of the clinical pulmonary infection score. Intensive Care Med 2010, 36:790-798.
• [106]Luyt CE, Guerin V, Combes A, Trouillet JL, Ayed SB, Bernard M, Gibert C, Chastre J: Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am J Respir Crit Care Med 2005, 171:48-53.
• [107]Seligman R, Meisner M, Lisboa TC, Hertz FT, Filippin TB, Fachel JM, Teixeira PJ: Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia. Crit Care 2006, 10:R125.
• [108]Su LX, Meng K, Zhang X, Wang HJ, Yan P, Jia YH, Feng D, Xie LX: Diagnosing ventilator-associated pneumonia in critically ill patients with sepsis. Am J Crit Care 2012, 21:e110-e119.
• [109]Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008, 177:498-505.
• [110]Linssen CF, Bekers O, Drent M, Jacobs JA: C-reactive protein and procalcitonin concentrations in bronchoalveolar lavage fluid as a predictor of ventilator- associated pneumonia. Ann Clin Biochem 2008, 45:293-298.
• [111]Hillas G, Vassilakopoulos T, Plantza P, Rasidakis A, Bakakos P: C-reactive protein and procalcitonin as predictors of survival and septic shock in ventilator-associated pneumonia. Eur Respir J 2010, 35:805-811.
• [112]Chastre J, Luyt CE, Trouillet JL, Combes A: New diagnostic and prognostic markers of ventilator-associated pneumonia. Curr Opin Crit Care 2006, 12:446-451.
• [113]Conway Morris A, Kefala K, Wilkinson TS, Moncayo-Nieto OL, Dhaliwal K, Farrell L, Walsh TS, Mackenzie SJ, Swann DG, Andrews PJ, Anderson N, Govan JR, Laurenson IF, Reid H, Davidson DJ, Haslett C, Sallenave JM, Simpson AJ: Diagnostic importance of pulmonary interleukin-1beta and interleukin-8 in ventilator-associated pneumonia. Thorax 2010, 65:201-207.
• [114]Luyt CE, Combes A, Trouillet JL, Chastre J: Value of the serum procalcitonin level to guide antimicrobial therapy for patients with ventilator-associated pneumonia. Semin Respir Crit Care Med 2011, 32:181-187.
• [115]Pugh R, Grant C, Cooke RP, Dempsey G: Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev 2011:CD007577.
• [116]Goulden BE: Assessment of the usefulness of the examination of a gram smear of fresh uncentrifuged urine in the determination of significant bacteriuria in dogs. N Z Vet J 1968, 16:1-2.
• [117]Jorgensen JH, Jones PM: Comparative evaluation of the Limulus assay and the direct Gram stain for detection of significant bacteriuria. Am J Clin Pathol 1975, 63:142-148.
• [118]Robins DG, Rogers KB, White RH, Osman MS: Urine microscopy as an aid to detection of bacteriuria. Lancet 1975, 1:476-478.
• [119]Crout FV, Tilton RC: Rapid screening of urine for significant bacteriuria by Gram stain, acridine orange stain, and the Autobac MTS system. Diagn Microbiol Infect Dis 1984, 2:179-186.
• [120]Tilton RE, Tilton RC: Automated direct antimicrobial susceptibility testing of microscopically screened urine cultures. J Clin Microbiol 1980, 11:157-161.
• [121]Wilson ML, Gaido L: Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis 2004, 38:1150-1158.
• [122]Wiwanitkit V, Udomsantisuk N, Boonchalermvichian C: Diagnostic value and cost utility analysis for urine Gram stain and urine microscopic examination as screening tests for urinary tract infection. Urol Res 2005, 33:220-222.
• [123]Williams GJ, Macaskill P, Chan SF, Turner RM, Hodson E, Craig JC: Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis. Lancet Infect Dis 2010, 10:240-250.
• [124]Lewis JF, Alexander J: Microscopy of stained urine smears to determine the need for quantitative culture. J Clin Microbiol 1976, 4:372-374.
• [125]La Scola B, Raoult D: Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. PLoS One 2009, 4:e8041.
• [126]Ferroni A, Suarez S, Beretti JL, Dauphin B, Bille E, Meyer J, Bougnoux ME, Alanio A, Berche P, Nassif X: Real-time identification of bacteria and Candida species in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 2010, 48:1542-1548.
• [127]Ferreira L, Sanchez-Juanes F, Gonzalez-Avila M, Cembrero-Fucinos D, Herrero-Hernandez A, Gonzalez-Buitrago JM, Munoz-Bellido JL: Direct identification of urinary tract pathogens from urine samples by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 2010, 48:2110-2115.
• [128]Wang XH, Zhang G, Fan YY, Yang X, Sui WJ, Lu XX: Direct identification of bacteria causing urinary tract infections by combining matrix-assisted laser desorption ionization-time of flight mass spectrometry with UF-1000i urine flow cytometry. J Microbiol Methods 2013, 92:231-235.
• [129]Burillo A, Rodriguez-Sanchez B, Ramiro A, Cercenado E, Rodriguez-Creixems M, Bouza E: Gram-stain plus MALDI-TOF MS (matrix-assisted laser desorption ionization-time of flight mass spectrometry) for a rapid diagnosis of urinary tract infection. PLoS One 2014, 9:e86915.
• [130]Oakes AR, Badger R, Grove DI: Comparison of direct and standardized testing of infected urine for antimicrobial susceptibilities by disk diffusion. J Clin Microbiol 1994, 32:40-45.
• [131]Kallenius G, Dornbusch K, Hallander HO, Jakobsson K: Comparison of direct and standardized antibiotic susceptibility testing in bacteriuria. Chemother 1981, 27:99-105.
• [132]Dupeyron CM, Guillemin GA, Leluan GJ: Rapid diagnosis of gram negative urinary infections: identification and antimicrobial susceptibility testing in 24 hours. J Clin Pathol 1986, 39:208-211.
• [133]Johnson JR, Tiu FS, Stamm WE: Direct antimicrobial susceptibility testing for acute urinary tract infections in women. J Clin Microbiol 1995, 33:2316-2323.
• [134]Gillenwater JY, Clark MM: Tentative direct antimicrobial susceptibility testing in urine. J Urol 1996, 156:149-153.
• [135]Bronnestam R: Direct antimicrobial susceptibility testing in bacteriuria. APMIS 1999, 107(4):437-444.
• [136]Breteler KB, Rentenaar RJ, Verkaart G, Sturm PD: Performance and clinical significance of direct antimicrobial susceptibility testing on urine from hospitalized patients. Scand J Infect Dis 2011, 43:771-776.
• [137]Baron EJ, Miller JM, Weinstein MP, Richter SS, Gilligan PH, Thomson RB Jr, Bourbeau P, Carroll KC, Kehl SC, Dunne WM, Robinson-Dunn B, Schwartzman JD, Chapin KC, Snyder JW, Forbes BA, Patel R, Rosenblatt JE, Pritt BS: A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clin Infect Dis 2013, 57:e22-e121.
• [138]Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan EL, Montoya JG, Wade JC: Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005, 41:1373-1406.
• [139]Wolk DM, Struelens MJ, Pancholi P, Davis T, Della-Latta P, Fuller D, Picton E, Dickenson R, Denis O, Johnson D, Chapin K: Rapid detection of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in wound specimens and blood cultures: multicenter preclinical evaluation of the Cepheid Xpert MRSA/SA skin and soft tissue and blood culture assays. J Clin Microbiol 2009, 47:823-826.
• [140]Dubouix-Bourandy A, de Ladoucette A, Pietri V, Mehdi N, Benzaquen D, Guinand R, Gandois JM: Direct detection of Staphylococcus osteoarticular infections by use of Xpert MRSA/SA SSTI real-time PCR. J Clin Microbiol 2011, 49:4225-4230.
• [141]Titecat M, Loiez C, Senneville E, Wallet F, Dezeque H, Legout L, Migaud H, Courcol RJ: Evaluation of rapid mecA gene detection versus standard culture in staphylococcal chronic prosthetic joint infections. Diagn Microbiol Infect Dis 2012, 73:318-321.
• [142]Petts DN, Lane A, Kennedy P, Hadfield SG, McIllmurray MB: Direct detection of groups A, C and G streptococci in clinical specimens by a trivalent colour test. Eur J Clin Microbiol Infect Dis 1988, 7:34-39.
• [143]de Quirós JCL B, Moreno S, Muñoz P, Rodríguez-Créixems M, Catalán P, Bouza E: Antigen detection in the rapid diagnosis of severe extrapharyngeal infections caused by group A streptococcus. Infect Dis Clin Pract 1992, 1:372-376.
• [144]Garcia-Lechuz Moya JM: Clinical microbiological case: a Nicaraguan woman with skin lesions on the left elbow and foot. Clin Microbiol Infect 2001, 7:84-87.
• [145]Sinclair A, Xie X, Teltscher M, Dendukuri N: Systematic review and meta-analysis of a urine-based pneumococcal antigen test for diagnosis of community-acquired pneumonia caused by Streptococcus pneumoniae. J Clin Microbiol 2013, 51(7):2303-2310.
• [146]de Ory F, Minguito T: Comparison of five commercial assays for the detection of Legionella pneumophila antigens in urine. Enferm Infec Microbiol Clin 2009, 27(2):81-84.
• [147]Emmadi R, Boonyaratanakornkit JB, Selvarangan R, Shyamala V, Zimmer BL, Williams L, Bryant B, Schutzbank T, Schoonmaker MM, Amos Wilson JA, Hall L, Pancholi P, Bernard K: Molecular methods and platforms for infectious diseases testing a review of FDA-approved and cleared assays. J Mol Diagn 2011, 13(6):583-604.
• [148]Tenover FC: Potential impact of rapid diagnostic tests on improving antimicrobial use. Ann N Y Acad Sci 2010, 1213:70-80.