The NOVA score: a proposal to reduce the need for transesophageal echocardiography in patients with enterococcal bacteremia.

BACKGROUND: Frequency of enterococcal bloodstream infection (E-BSI) is increasing, and the number of episodes complicated by infective endocarditis (IE) varies. Performing transesophageal echocardiography (TEE) in all patients with E-BSI is costly and time-consuming. Our objectives were to identify patients with E-BSI who are at very low risk of enterococcal IE (and therefore do not require TEE) and to compare the outcome of E-BSI in patients with/without IE. METHODS: Between September 2003 and October 2012, we performed a prospective cohort study (all patients with E-BSI) and a case-control study (patients with/without enterococcal IE) in our center. RESULTS: We detected 1515 patients with E-BSI and 65 with enterococcal IE (4.29% of all episodes of E-BSI, 16.7% of patients with E-BSI who underwent transthoracic echocardiography, and 35.5% of all patients with E-BSI who underwent TEE). We developed a bedside predictive score for enterococcal IE-Number of positive blood cultures, Origin of the bacteremia, previous Valve disease, Auscultation of heart murmur (NOVA) score-based on the following variables: Number of positive blood cultures (3/3 blood cultures or the majority if more than 3), 5 points; unknown Origin of bacteremia, 4 points; prior heart Valve disease, 2 points; Auscultation of a heart murmur, 1 point (receiver operating characteristic = 0.83). The best cutoff corresponded to a score ≥4 (sensitivity, 100%; specificity, 29%). A score <4 points suggested a very low risk for enterococcal IE and that TEE could be obviated. CONCLUSIONS: Enterococcal IE may be more frequent than generally thought. Depending on local prevalence of endocarditis, application of the NOVA score may safely obviate echocardiography in 14%-27% of patients with E-BSI.

Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Nontuberculous Mycobacteria from Clinical Isolates.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of nontuberculous mycobacterial (NTM) isolates was evaluated in this study. Overall, 125 NTM isolates were analyzed by MALDI-TOF and GenoType CM/AS. Identification by 16S rRNA/hsp65 sequencing was considered the gold standard. Agreements between MALDI-TOF and GenoType CM/AS with the reference method were, respectively, 94.4% and 84.0%. In 17 cases (13.6%), results provided by GenoType and MALDI-TOF were discordant; however, the reference method agreed with MALDI-TOF in 16/17 cases (94.1%; P = 0.002).

Occult bloodstream infections in adults: a "benign" entity.

BACKGROUND: Patients with septic episodes whose blood cultures turn positive after being sent home from emergency departments (EDs) are recognized as having occult bloodstream infections (BSI). The incidence, etiology, clinical circumstances, and outcome of occult BSI in children are well known, but, to our knowledge, data in adult patients are scarce. We analyzed the episodes of occult BSI in adult patients at our institution. METHODS: This is a retrospective cohort study (September 2010 to September 2012), in adult patients discharged from the ED in whom blood cultures turned positive. Patients were evaluated according to a preestablished protocol. RESULTS: We recorded 4025 cases of significant BSI in the ED and 113 patients with adult occult BSI. In other words, the incidence of occult BSI in the ED was 2.8 per 100 episodes. The predominant microorganisms were gram-negative bacteria (57%); Escherichia coli was the most common (41%), followed by gram-positive bacteria (29%), anaerobes (6.9%), polymicrobial (6.1%), and yeasts (0.8%). The most frequent suspected origin was urinary tract infection (53%), and most infections were community acquired (63.7%). Of the 105 patients that we were able to trace, 54 (42.5%) were asymptomatic and were receiving adequate antibiotic treatment at the time of the call, and 65 (51.2%) had persistent fever or were not receiving adequate antibiotic treatment. CONCLUSIONS: Occult BSI is relatively common in patients in the adult ED. Despite the need for readmission of a fairly high proportion of patients, occult BSI behaves as a relatively benign entity.

Can MALDI-TOF mass spectrometry be used with intravascular catheters?

INTRODUCTION: The use of the matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry has shown to be effective and fast in some clinical specimens for the identification of colonizing microorganisms. The objective of the study was to analyze the validity values for the prediction of colonization and catheter-related bloodstream infection (C-RBSI) of the MALDI-TOF mass spectrometry performed at all intravascular catheters that arrived in the microbiology laboratory. METHODS: Catheter tips (after performing the roll-plate technique) were tested by MALDI-TOF mass spectrometry during a period of 3-months. The gold standard for colonization and C-RBSI were, respectively: the presence of ≥15cfu/plate in the catheter tip culture; and the isolation of the same microorganism(s) in blood cultures as well as in the colonized catheter (during the 7days before or after catheter withdrawal). RESULTS: A total of 182 intravascular catheters were collected. The overall colonization rate detected by roll-plate technique and MAL-TOF mass spectrometry was 31.9% and 32.4%, respectively. Overall, there were 33 (18.1%) episodes of C-RBSI. The validity values of the MALDI-TOF mass spectrometry for the identification of colonization and C-RBSI were, respectively: sensitivity (69.0%/66.7%), specificity (84.7%/75.2%), positive predictive value (65.6%/36.1%), and negative predictive value (86.8%/92.6%). Conclusion MALDI-TOF mass spectrometry could be an alternative diagnostic tool for ruling out C-RBSI. However, despite it showing to be faster than conventional culture, future studies are required in order to improve the pre-analytical process.

Endemic genotypes of Candida albicans causing fungemia are frequent in the hospital.

Genotyping of Candida albicans strains causing candidemia can uncover the presence of endemic genotypes in the hospital. Using a highly reproducible and discriminatory microsatellite marker panel, we studied the genetic diversity of 217 C. albicans isolates from the blood cultures of 202 patients with candidemia (from January 2007 to December 2011). Each isolate represented 1 candidemia episode. Multiple episodes were defined as the isolation of C. albicans in further blood cultures taken ≥7 days after the last isolation in blood culture. Of the 202 patients, 188 had 1 episode, 13 had 2 episodes, and 1 had 3 episodes. Identical genotypes showed the same alleles for all 6 markers. The genotypes causing both episodes were identical in most patients with 2 episodes (11/13; 84.6%). In contrast, 2 different genotypes were found in the patient with 3 episodes, one causing the first and second episodes and the other causing the third episode (isolated 6 months later). We found marked genetic diversity in 174 different genotypes: 155 were unique, and 19 were endemic and formed 19 clusters (2 to 6 patients per cluster). Up to 25% of the patients were infected by endemic genotypes that infected 2 or more different patients. Some of these endemic genotypes were found in the same unit of the hospital, mainly neonatology, whereas others infected patients in different wards.

The value of combining blood culture and SeptiFast data for predicting complicated bloodstream infections caused by Gram-positive bacteria or Candida species.

Management of complicated bloodstream infections requires more aggressive treatment than uncomplicated bloodstream infections. We assessed the value of follow-up blood culture in bloodstream infections caused by Staphylococcus aureus, Enterococcus spp., Streptococcus spp., and Candida spp. and studied the value of persistence of DNA in blood (using SeptiFast) for predicting complicated bloodstream infections. Patients with bloodstream infections caused by these microorganisms were enrolled prospectively. After the first positive blood culture, samples were obtained every third day to perform blood culture and SeptiFast analyses simultaneously. Patients were followed to detect complicated bloodstream infection. The study sample comprised 119 patients. One-third of the patients developed complicated bloodstream infections. The values of persistently positive tests to predict complicated bloodstream infections were as follows: SeptiFast positive samples (sensitivity, 56%; specificity, 79.5%; positive predictive value, 54%; negative predictive value, 80.5%; accuracy, 72.3%) and positive blood cultures (sensitivity, 30.5%; specificity, 92.8%; positive predictive value, 64%; negative predictive value, 75.5%; accuracy, 73.9%). Multivariate analysis showed that patients with a positive SeptiFast result between days 3 and 7 had an almost 8-fold-higher risk of developing a complicated bloodstream infection. In S. aureus, the combination of both techniques to exclude endovascular complications was significantly better than the use of blood culture alone. We obtained a score with variables selected by the multivariate model. With a cutoff of 7, the negative predictive value for complicated bloodstream infection was 96.6%. Patients with a positive SeptiFast result between days 3 and 7 after a positive blood culture have an almost 8-fold-higher risk of developing complicated bloodstream infections. A score combining clinical data with the SeptiFast result may improve the exclusion of complicated bloodstream infections.

Mixed bloodstream infections involving bacteria and Candida spp.

OBJECTIVES: Polymicrobial bloodstream infection (BSI) is an imprecisely defined entity purportedly associated with a worse outcome than monomicrobial BSI. This study examines trends in BSI episodes caused by bacteria and Candida spp. (mixed-BSI) in a large teaching hospital. METHODS: All episodes of BSI from January 2000 to December 2010 were reviewed. Three groups (n = 54 each) of patients were compared: all adults with mixed-BSI from January 2006 to December 2010 (cases) and randomly selected patients with polybacterial BSI (polyB-BSI) (Control 1) or Candida spp. BSI (Candida-BSI) (Control 2) in this same period. RESULTS: A total of 139 episodes of mixed-BSI were recorded (0.7% of all BSI, 6.9% of all poly-BSI and 18.0% of all Candida-BSI episodes). The incidence of mixed-BSI was 0.21 cases/1000 admissions, increasing from 0.08 (2000) to 0.34 (2010) cases/1000 admissions (P = 0.007). Mixed-BSI represented 11.8% and 22.9% of all episodes of candidaemia in 2000 and 2010, respectively (P = 0.011). Compared with polyB-BSI, mixed-BSI patients showed fewer malignancies, more frequent nosocomial or intravenous catheter BSI source and less frequent intra-abdominal origin, were more frequently admitted to an intensive care unit (ICU), received more antimicrobials and showed a longer hospital stay and higher mortality. Compared with Candida-BSI, mixed-BSI patients showed more severe underlying diseases, were more frequently admitted to an ICU or oncology-haematology unit, showed a higher APACHE II score, more often progressed to septic shock or multiorgan failure and received more antimicrobials. Mortality was similar. CONCLUSIONS: Mixed-BSI is a rare, distinct infection with a worse prognosis than polyB-BSI. We were unable to detect differences in the prognosis of mixed-BSI when compared with Candida-BSI.

Does identification to species level provide sufficient evidence to confirm catheter-related fungemia caused by Candida albicans?

We retrospectively studied 22 patients with catheter-related candidemia caused by Candida albicans. Strains isolated simultaneously from blood and catheter tips were genotyped using six microsatellite markers. Matches between genotypes of isolates recovered from both sample sources were found in 20/22 (91%) patients. Consequently, identification of the same species from both the catheter tip and blood could be used to confirm catheter-related candidemia.

Vancomycin MICs do not predict the outcome of methicillin-resistant Staphylococcus aureus bloodstream infections in correctly treated patients.

BACKGROUND: Recent studies have reported a greater probability of vancomycin treatment failure in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections caused by strains with a vancomycin MIC ≥ 1.5 mg/L. However, previous reports included patients treated without adjustments based on vancomycin serum levels and with different methods to evaluate MICs, which may render different results. METHODS: Over a 5 year period (2005-09), vancomycin MICs were determined for 361 MRSA isolates recovered from 309 patients with bloodstream infection using microdilution and the Etest simultaneously. The relationship between the vancomycin MICs determined by each method was assessed. To assess the outcome of patients treated with vancomycin, 104 patients for whom serum vancomycin levels had been determined were selected. RESULTS: The percentage of MRSA strains with MIC values ≥ 1.5 mg/L according to the Etest was 66.5% compared with only 3.6% according to microdilution. No correlation between mortality and any MIC value obtained with either method was observed, independently of the vancomycin serum levels measured. CONCLUSIONS: There is a poor correlation between vancomycin MIC values obtained by microdilution and by Etest. No association between mortality rate and any MIC value was observed, not even in patients with suboptimal vancomycin trough serum levels. These data do not support replacing or complementing the standard microdilution test with the Etest for determination of MICs of vancomycin in microbiology laboratories.

Prevention, Diagnosis and Management of Post-Surgical Mediastinitis in Adults Consensus Guidelines of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES).

This is a consensus document of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES). These three entities have brought together a multidisciplinary group of experts that includes anaesthesiologists, cardiac and cardiothoracic surgeons, clinical microbiologists, infectious diseases and intensive care specialists, internal medicine doctors and radiologists. Despite the clinical and economic consequences of sternal wound infections, to date, there are no specific guidelines for the prevention, diagnosis and management of mediastinitis based on a multidisciplinary consensus. The purpose of the present document is to provide evidence-based guidance on the most effective diagnosis and management of patients who have experienced or are at risk of developing a post-surgical mediastinitis infection in order to optimise patient outcomes and the process of care. The intended users of the document are health care providers who help patients make decisions regarding their treatment, aiming to optimise the benefits and minimise any harm as well as the workload.

How many lumens should be cultured in the conservative diagnosis of catheter-related bloodstream infections?

BACKGROUND: Recent practice guidelines for the diagnosis of catheter-related bloodstream infection (CRBSI) describe as an "unresolved issue" the number of lumens from which blood culture specimens should be drawn to make a conservative diagnosis of CRBSI. Our objective was to determine how many CRBSI episodes would be missed if not all catheter lumens were sampled. METHODS: We performed a retrospective study (1 January 2003-31 May 2009) in patients with microbiologically proven CRBSI in which all available catheter lumens (those that did not contain clots) were used to draw blood culture samples. We calculated the number of episodes that would have been missed in double- and triple-lumen catheters if the culture of samples obtained from 1 lumens had been eliminated. RESULTS: We studied 171 episodes of proven CRBSI in 154 patients. Overall, if 1 lumen-associated culture had been eliminated for both double-lumen and triple-lumen catheters, we would have missed 27.2% and 15.8% of episodes of CRBSI, respectively. If we had eliminated 2 cultures for triple-lumen catheters, 37.3% of episodes would have been missed. CONCLUSIONS: Samples for blood culture should be obtained through all catheter lumens to establish a diagnosis of CRBSI.

Rapid antifungal susceptibility determination for yeast isolates by use of Etest performed directly on blood samples from patients with fungemia.

We prospectively determined the antifungal susceptibility of yeast isolates causing fungemia using the Etest on direct blood samples (195 prospectively collected and 133 laboratory prepared). We compared the Etest direct (24 h of incubation) with CLSI M27-A3 and the standard Etest methodologies for fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, and amphotericin B. Strains were classified as susceptible, resistant, or nonsusceptible using CLSI breakpoints (voriconazole breakpoints were used for posaconazole and isavuconazole). Categorical errors between Etest direct and CLSI M27-A3 for azoles were mostly minor. No errors were detected for caspofungin, and high percentages of major errors were detected for amphotericin B. For the azoles, false susceptibility (very major errors) was found in only two (0.6%) isolates (Candida tropicalis and C. glabrata). False resistance (major errors) was detected in 46 (14%) isolates for the three azoles (in 23 [7%] after excluding posaconazole). Etest direct of posaconazole yielded a higher number of major errors than the remaining azoles, especially for C. glabrata, Candida spp., and other yeasts. Excluding C. glabrata, Candida spp., and other yeasts, the remaining species did not yield major errors. Etest direct for fluconazole, voriconazole, isavuconazole, and caspofungin shows potential as an alternative to the CLSI M27-A3 procedure for performing rapid antifungal susceptibility tests on yeast isolates from patients with fungemia. Etest direct is a useful tool to screen for the presence of azole-resistant and caspofungin-nonsusceptible strains.

Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance.

BACKGROUND: The significance of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is unknown. Using a multinational collection of isolates from methicillin-resistant S. aureus (MRSA) infective endocarditis (IE), we characterized patients with IE with and without hVISA, and we genotyped the infecting strains. METHODS: MRSA bloodstream isolates from 65 patients with definite IE from 8 countries underwent polymerase chain reaction (PCR) for 31 virulence genes, pulsed-field gel electrophoresis, and multilocus sequence typing. hVISA was defined using population analysis profiling. RESULTS: Nineteen (29.2%) of 65 MRSA IE isolates exhibited the hVISA phenotype by population analysis profiling. Isolates from Oceania and Europe were more likely to exhibit the hVISA phenotype than isolates from the United States (77.8% and 35.0% vs 13.9%; P < .001). The prevalence of hVISA was higher among isolates with a vancomycin minimum inhibitory concentration of 2 mg/L (P = .026). hVISA-infected patients were more likely to have persistent bacteremia (68.4% vs 37.0%; P = .029) and heart failure (47.4% vs 19.6%; P = .033). Mortality did not differ between hVISA- and non-hVISA-infected patients (42.1% vs 34.8%, P = .586). hVISA and non-hVISA isolates were genotypically similar. CONCLUSIONS: In these analyses, the hVISA phenotype occurred in more than one-quarter of MRSA IE isolates, was associated with certain IE complications, and varied in frequency by geographic region.

Empirical treatment of candidemia in intensive care units: fluconazole or broad-spectrum antifungal agents?

The fear of candidemia caused by a fluconazole-resistant species of Candida is causing many intensive care units (ICUs) to switch empiric therapy from this drug to broad-spectrum antifungal agents. We studied the epidemiology and antifungal susceptibility of Candida isolates involved in cases of candidemia among adult and pediatric patients in ICUs from 1984 to 2006. We documented 307 episodes of candidemia in 307 patients, of which only eight episodes (2.6%) were caused by a fluconazole-resistant isolate. At least three of the eight patients from whom fluconazole-resistant strains were recovered had recently received fluconazole. Overall, only 1.6% of the episodes of candidemia caused by fluconazole-resistant strains (five patients) occurred in individuals with no evidence of previous fluconazole administration. In conclusion, the use of broad-spectrum antifungal agents is not justified in ICUs with a low proportion of candidemia episodes caused by fluconazole-resistant strains of Candida.

Bloodstream infections: evolution and trends in the microbiology workload, incidence, and etiology, 1985-2006.

Information available on bloodstream infection (BSI) is usually restricted to short periods of time, certain clinical backgrounds, or specific pathogens, or is just outdated. We conducted the current prospective study of patients with BSI in a 1750-bed teaching hospital to evaluate workload trends and the incidence and etiology of BSI in a general hospital during the last 22 years, including the acquired immunodeficiency syndrome (AIDS) era. The main outcome measures were laboratory workload, trends in incidence per 1000 admissions and per 100,000 population of different microorganisms, and the impact of the human immunodeficiency virus (HIV) epidemic in the period 1985-2006.From 1985 to 2006 we had 27,419 episodes of significant BSI (22,626 patients). BSI incidence evolved from 16.0 episodes to 31.2/1000 admissions showing an annual increase of 0.83 episodes/1000 admissions (95% confidence interval, 0.61-1.05; p < 0.0001). The evolution of the incidence per 1000 admissions and per 100,000 population of different groups of microorganisms was as follows: Gram positives 8.2 to 15.7/1000 admissions and 66.8 to 138.3/100,000 population; Gram negatives 7.8 to 16.2/1000 admissions and 63.5 to 141.9/100,000 population; anaerobes 0.5 to 1.3/1000 admissions and 4.1 to 11.7/100,000 population; and fungi 0.2 to 1.5/1000 admissions and 1.7 to 12.5/100,000 population. All those differences were statistically significant. We observed the emergence of multiresistant Gram-positive and Gram-negative microorganisms. At least 2484 episodes of BSI (9.1%) occurred in 1822 patients infected with HIV. The incidence of BSI in HIV-infected patients increased from 1985 and reached a peak in 1995 (17.6% of BSI). Since 1995, the decrease was continuous, and in 2006 only 3.9% of all BSI episodes occurred in HIV-positive patients in our institution. We conclude that the BSI workload has increased in modern microbiology laboratories. Gram-positive pathogens have overtaken other etiologic agents of BSI. Our observation shows the remarkable escalation of some resistant pathogens, and the rise and relative fall of BSI in patients with HIV.

Heart valves should not be routinely cultured.

Heart valve (HV) culture is one of the major Duke criteria for the diagnosis of definite infectious endocarditis (IE). However, previous series suggest that heart valve culture does not have good sensitivity (7.8 to 17.6%) and may be contaminated during manipulation. Our goal was to establish the value of routine cultures of heart valves in patients with and without IE. From 2004 to 2006, resected heart valves were systematically cultured according to standard procedures. The definition and etiology of IE were based on the Duke criteria and on valve PCR of specimens from blood culture-negative patients. Bacterial and fungal broad-range PCR was performed. A total of 1,101 heart valves were studied: 1,030 (93.6%) from patients without IE and 71 (6.4%) from patients with IE (42 patients). Overall, 321 (29.2%) cultures were positive (28/71 [39.4%] IE cases and 293/1,030 [28.4%] non-IE). All IE patients with negative heart valve cultures had received antimicrobial therapy. The yield of culture of heart valves for IE diagnosis was as follows: sensitivity, 25.4%; specificity, 71.6%; positive predictive value (PPV), 5.8%; and negative predictive value, 93.3%. Because of its poor sensitivity and PPV, valve cultures should not be performed for patients without a clinical suspicion of IE. For patients with confirmed IE, heart valve cultures should be interpreted with caution.

Gram-negative bloodstream infections.

Over the last 22 years we have prospectively recorded data for bloodstream infections (BSIs) in our institution. We reflect the experience of a tertiary teaching hospital with 1750-2500 beds that served a population ranging during the study period from 650,000 to 750,000 inhabitants. Definitions and microbiological methods were standard. The microbiological workload of blood cultures was analysed and the evolution of the incidence of BSI episodes, provided as episodes per 1000 admissions and per 100000 inhabitants, is reported. During the study period, our institution had over one million admissions; blood culturing increased from 299 blood cultures/1000 admissions in the year 1985 to 720/1000 admissions in 2006. Overall, there were 65475 blood cultures with recovery of significant microorganisms, representing 27 419 episodes of significant BSI (22626 patients). The present paper describes the Gram-negative organisms recovered from the blood cultures and discusses their clinical significance.

Mixed fungemia: incidence, risk factors, and mortality in a general hospital.

BACKGROUND: Fungemia has been historically considered to be a disease caused by a single Candida species; the detection of >1 species of yeast in circulating blood was distinctly uncommon using traditional microbiological procedures. We describe episodes of mixed fungemia (MF), detected between 1985 and 2006, in a large teaching hospital. METHODS: The study was divided into 2 periods that were separated by the introduction, in January 2005, of the CHROmagar Candida medium (CHROMagar) for the routine subculturing of blood cultures in which yeast has been identified. Overall, we documented 747 cases of fungemia. During the first period (1985-1994), we identified 217 episodes of fungemia and no single episode of MF; during the second period (1995-2006), 15 episodes of MF were detected among 530 episodes of fungemia (2.8%). Candida albicans was isolated in 13 patients, non-albicans species of Candida in 16 patients, and Saccharomyces cerevisiae in 1 patient. Each episode of MF was compared with 2 control episodes of monomicrobial fungemia. RESULTS: Patients with MF had more frequently experienced organ transplantation (13% vs. 0%) and surgery (60% vs. 27%), had less frequently received parenteral nutrition (40% vs. 70%) or had intravenous lines (80% vs. 100%), and had a lower incidence of shock (6% vs. 37%) and a lower mortality (20% vs. 53%). CONCLUSIONS: Despite the introduction of chromogenic agar, MF is still an uncommon disease and has a less severe outcome than does monomicrobial candidemia.