Breakthrough candidemia after the introduction of broad spectrum antifungal agents: A 5-year retrospective study.

Candidemia is the main invasive fungal disease among hospitalized patients. Several breakthrough candidemia (BrC) cases have been reported, but few studies evaluate the epidemiology, risk factors, molecular characterization, antifungal susceptibility profile and outcome of those patients, especially in developing countries and including patients using broad spectrum antifungals. We conducted a retrospective study from 2011 to 2016, including patients aged 12 years or older with candidemia. Epidemiological characteristics and risk factors for candidemia were evaluated and compared with patients with BrC using univariate and multivariate analysis. Sequential Candida isolates from BrC were identified by internal transcribed spacer sequencing, genotyped with amplified fragment length polymorphism fingerprinting (AFLP), and tested for antifungal susceptibility. From 148 candidemia episodes, 27 breakthrough episodes (18%) were identified, with neutropenia and mucositis being independent risk factors for BrC. Candida non-albicans was more frequent in the BrC group (P < .001). AFLP showed high correlation with conventional methods of identification among breakthrough isolates and a high genetic similarity among isolates from the same patient was observed. C. albicans was the most susceptible species with low MIC values for all antifungal agents tested. In contrast, we found isolates of C. glabrata, C. parapsilosis and C. tropicalis resistant to triazoles and echinocandins. In conclusion, BrC occurred mainly in severely immunosuppressed patients, with neutropenia and mucositis. Mortality did not differ between the groups. Candida non-albicans species were more recovered from BrC, with C. albicans being the most susceptible to antifungals.

Human-to-human transmission of Brucella - a systematic review.

OBJECTIVE: The most common form of transmitting human brucellosis is through contaminated food or direct contact with infected animals. Human-to-human transmission (HHT) has been described as isolated case reports. The aim of this systematic review was to describe all cases of HHT of human brucellosis reported in the medical literature. METHODS: A literature search was conducted using PubMed, Scopus and Scielo databases using specific search terms published until March 2016. Two investigators independently determined study eligibility. All clinical data were evaluated to construct a table comprising the most important clinical aspects, age, gender, confirmed infection and detection method, transmission method and HHT confirmation and potential source of infection for human transmission. No statistical method was employed in this study. RESULTS: The initial search resulted in 615 publications, but only 35 were included. 45 brucellosis HHT cases were identified. 61% of patients who acquired brucellosis from another human were <1 year old (newborn and breastfeeding). Other cases include sexual transmission, blood transfusion, bone marrow transplantation and aerosol from an infected patient. Most patients (40/45) presented symptoms upon diagnosis. Diagnostic tests included culture, molecular methods and serum testing. CONCLUSION: Human brucellosis is a disease liable to transmission between humans by placental barrier, lactation, sexual and tissues such as blood and bone marrow. The indication for screening in tissue banks, transplants, blood and pregnancy is not yet established.

Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B.

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.

Phenotypic and molecular characterization of 942 carbapenem-resistant Enterobacteriaceae (CRE) in southern Brazil.

Carbapenem-resistant Enterobacteriaceae (CRE) is a major international health problem, and its identification in developing countries is based exclusively on phenotypic methods. The aim of this study was to assess the sensitivity and related parameters of the modified Hodge test (MHT). The assessment was performed in a large number of isolates obtained from different hospitals in several cities of a south Brazilian state. Bacterial species were identified using an automated method. The MHT was performed according to the guidelines set by the CLSI. The gene blaKPC was amplified in order to confirmation CRE expression. The sensitivity, specificity, positive, and negative predictive values were calculated. A total of 942 isolates were submitted to the reference laboratory for confirmation; 143 showed a negative MHT (15.18%) result, while 784 were positive (83.23%), and 15 samples displayed an indeterminate MHT (1.59%) result. All samples expressed the KPC-2 enzyme. Sensitivity, specificity, positive, and negative predictive percentiles were 99%, 89%, 98%, and 99% respectively. We conclude that the modified Hodge test is a reliable test for the prediction of KPC-producing bacteria.

Positive tip culture with Candida and negative blood culture: to treat or not to treat? A systematic review with meta-analysis.

BACKGROUND: Invasive candidiasis is a major invasive fungal infection. It has high lethality, and even higher if not treated early. There is no consensus on antifungal treatment in patients with positive catheter tip culture for Candida spp. The objective of this study was to evaluate the impact of antifungal therapy and mortality of patients with positive culture for Candida spp. in catheter tip that have negative blood culture. METHODS: The PubMed database was searched to identify articles related to Candida and catheter. Articles with adequate data were included. RESULTS: Of 1208 studies initially screened, 5 met the selection criteria. All were retrospective studies. In all, 265 patients were evaluated for outcomes 'candidemia' and 'invasive candidiasis' and 158 for the outcome 'mortality.' Antifungal therapy had no impact on the development of invasive fungal disease (Odds ratio (OR) = 1.41; 95% confidence interval (CI) = 0.56-3.52). Also there was no benefit of therapy on mortality (OR = 1.02; 95% CI = 0.54-1.95). CONCLUSION: Due to the poor quality of the studies no conclusion can be made. Randomized prospective studies are needed to better evaluate this therapeutic strategy.

Cross-sectional study for COVID-19-related mortality predictors in a Brazilian state-wide landscape: the role of demographic factors, symptoms and comorbidities.

OBJECTIVE: The Brazilian state of Paraná has suffered from COVID-19 effects, understanding predictors of increased mortality in health system interventions prevent hospitalisation of patients. We selected the best models to evaluate the association of death with demographic characteristics, symptoms and comorbidities based on three levels of clinical severity for COVID-19: non-hospitalised, hospitalised non-ICU ward and ICU ward. DESIGN: Cross-sectional survey using binomial mixed models. SETTING: COVID-19-positive cases diagnosed by reverse transcription-PCR of municipalities located in Paraná State. PATIENTS: Cases of anonymous datasets of electronic medical records from 1 April 2020 to 31 December 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The best prediction factors were chosen based on criteria after a stepwise analysis using multicollinearity measure, lower Akaike information criterion and goodness-of-fit χ2 tests from univariate to multivariate contexts. RESULTS: Male sex was associated with increased mortality among non-hospitalised patients (OR 1.76, 95% CI 1.47 to 2.11) and non-ICU patients (OR 1.22, 95% CI 1.05 to 1.43) for symptoms and for comorbidities (OR 1.89, 95% CI 1.59 to 2.25, and OR 1.30, 95% CI 1.11 to 1.52, respectively). Higher mortality occurred in patients older than 35 years in non-hospitalised (for symptoms: OR 4.05, 95% CI 1.55 to 10.54; and for comorbidities: OR 3.00, 95% CI 1.24 to 7.27) and in hospitalised over 40 years (for symptoms: OR 2.72, 95% CI 1.08 to 6.87; and for comorbidities: OR 2.66, 95% CI 1.22 to 5.79). Dyspnoea was associated with increased mortality in non-hospitalised (OR 4.14, 95% CI 3.45 to 4.96), non-ICU (OR 2.41, 95% CI 2.04 to 2.84) and ICU (OR 1.38, 95% CI 1.10 to 1.72) patients. Neurological disorders (OR 2.16, 95% CI 1.35 to 3.46), neoplastic (OR 3.22, 95% CI 1.75 to 5.93) and kidney diseases (OR 2.13, 95% CI 1.36 to 3.35) showed the majority of increased mortality for ICU as well in the three levels of severity jointly with heart disease, diabetes and CPOD. CONCLUSIONS: These findings highlight the importance of the predictor's assessment for the implementation of public healthcare policy in response to the COVID-19 pandemic, mainly to understand how non-pharmaceutical measures could mitigate the virus impact over the population.

Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease.

Several recent reviews have suggested a role of oxidative stress in the pathophysiology of COVID-19, but its interplay with disease severity has not been revealed yet. In the present study, we aimed to investigate the association between the severity of COVID-19 and oxidative stress parameters. Clinical data of 77 patients with COVID-19 admitted to the hospital were analyzed and divided into moderate (n = 44) and severe (n = 33) groups based on their clinical condition. Production of oxidant (hydrogen peroxide) and defense antioxidants (total antioxidant capacity, reduced and oxidized glutathione, glutathione s-transferase), and oxidative damage (malondialdehyde, carbonyl, and sulfhydryl) were assessed using the serum samples. The results revealed that severe patients who presented high serum leukocyte count and CRP level stayed for a longer period in the hospital. However, there was no correlation observed between the oxidative stress parameters and degree of COVID-19 severity in the present study. In conclusion, these results indicate that the disease severity may not be a detrimental factor contributing to the changes in the redox profile of hospitalized patients with COVID-19.

Polymyxin B and colistin-the economic burden of nephrotoxicity against multidrug resistant bacteria.

BACKGROUND: Polymyxin B and colistin are nephrotoxic drugs used in the treatment of carbapenem-resistant Enterobacteriaceae. The aim of this study is to evaluate the burden of costs due to polymyxin associated AKI and propose a simulated break-even price for new therapies. METHODS: The pharmacoeconomic model is based on two large cross-sectional studies of polymyxin nephrotoxicity. Total direct costs in patients with and without renal failure were compared. The direct cost of each hemodialysis section (USD82.94) and daily hospital charges (USD934.85) were based on the values used in a major public hospital in the city where the clinical study was performed. The break-even price of new drugs was simulated considering eventual new drugs as effective as polymyxins, but less nephrotoxic in different percentages. Outcomes of patients after hospital discharge were not evaluated. RESULTS: Total direct cost of the group of patients who survived without AKI was significantly lower than total direct cost of the groups either with AKI or the group who died without AKI. There was a tendency of even higher costs in those who died with AKI and dialysis. Direct cost of hemodialysis was not as important as the longer hospitalization after sepsis. Considering daily cost of polymyxin is USD60, drugs with 50% less AKI could be considered cost-beneficial if the daily cost is lower than USD160. CONCLUSIONS: AKI in patients with carbapenem-resistant Enterobacteriaceae treated with polymyxin increases both length of stay in hospital and total costs.

Characterization of Decellularized Human Pericardium for Tissue Engineering and Regenerative Medicine Applications.

BACKGROUND: Pericardium tissue allograft can be used for surgical repair in several procedures. One of the tissue engineering strategies is the process of decellularization. This process decreases immunogenic response, but it may modify the natural extracellular matrix composition and behavior. OBJECTIVE: The aim of this study was to evaluate the effectiveness of cell removal, maintenance of extracellular matrix properties and mechanical integrity of decellularized human pericardium using a low concentration solution of sodium dodecyl sulfate. METHODS: Decellularization was performed with sodium dodecyl sulfate and ethylenediaminetetraacetic acid. Histological analysis, DNA quantification, evaluation of glycosaminoglycans and collagen were performed. Biomechanical assay was performed using tensile test to compare the decellularization effects on tissue properties of tensile strength, elongation and elastic modulus. P < 0.05 was considered significant. RESULTS: There was reduction in visible nuclei present in pericardium tissue after decellularization, but it retained collagen and elastin bundles similar to fresh pericardium. The DNA contents of the decellularized pericardium were significantly reduced to less than 511.23 ± 120.4 ng per mg of dry weight (p < 0.001). The biomechanical assay showed no significant difference for fresh or decellularized tissue. CONCLUSION: The decellularization process reduces cell content as well as extracellular matrix components without changing its biomechanical properties.

Seroprevalence of Toxoplasma gondii, cytomegalovirus and Epstein Barr virus in 578 tissue donors in Brazil.

This study aimed to verify the prevalence of IgG antibodies for Toxoplasma gondii, CMV, and EBV in tissue donors from different regions of Brazil between February 2016 and July 2017. In this retrospective study, 578 donors were evaluated from different regions of Brazil. The seroprevalence of T. gondii was 61.2%, CMV was 93%, and EBV was 98.3%. The seroprevalence increased with age, from 27.8% in donors younger than 18 years of age to 67.6% in those older than 60 years of age (p<0.05). The analysis of the seroprevalence of CMV and EBV showed similar percentages (>90%) among the different states, the interior and capital of Paraná state, sex, and age. The seroprevalence of CMV, EBV and TOXO is high in all groups and age in Brazilian donors of tissues.

Rhodotorula infection. A systematic review of 128 cases from literature.

Rhodotorula is an emerging opportunistic pathogen, particularly in immunocompromised patients. Many cases of fungemia associated with catheters, endocarditis, peritonitis, meningitis, and endophthalmitis are infections incited by this yeast. The main purpose of this study was to review all cases of Rhodotorula infection reported in the literature and to describe risk factors, underlying conditions and outcome. From 128 cases, 79% were fungemia (103 cases), 7% eye infections (nine cases) and 5% (six cases) peritonitis associated with continuous ambulatory peritoneal dialysis. Eighty seven percent of Rhodotorula infections are associated with underlying immunosuppression or cancer. The most common isolated risk factor associated with Rhodotorula infection was the use of a central venous catheter, which was found in 83.4% of Rhodotorula fungemia (86 cases). Rhodotorula mucilaginosa was the most common species of fungemia (74% of cases), followed by Rhodotorula glutinis with 7.7%. The species was not identified in 17% of the cases of fungemias. Amphotericin was the drug of choice in the treatment of fungemia and most of the eye infections were treated with topical amphotericin, although all patients lost their vision. All peritonitis cases associated with continous ambulatory peritoneal dialysis needed to have the Tenckoff catheter changed. The overall mortality of Rhodotorula infection was 12.6%.

Isolated lymphadenitis due to Histoplasma capsulatum diagnosed by fine-needle aspiration biopsy and immunohistochemistry.

In the disseminated form of histoplasmosis, isolation and further identification of Histoplasma capsulatum can be performed by several methods, namely, bone marrow aspiration, blood culture, and liver biopsy. Lymph node disease usually is diagnosed by excisional biopsy. Although fungal stains can identify this fungus, detection of specific antigens by immunohistochemistry shows a higher specificity and sensitivity. This approach can use the cell block method when the material is not sent to fungal cultures or fresh staining.

Cost-effectiveness of posaconazole in private and public Brazilian hospitals.

BACKGROUND: Posaconazole is used for the prophylaxis of invasive fungal disease (IFD). Previous studies have shown it to be cost-effective compared to fluconazole/itraconazole. However, posaconazole has never been economically evaluated in developing countries. AIMS: The aim of the present study was to perform a cost-effectiveness analysis of posaconazole compared to fluconazole in public (SUS) and private hospitals (PHS) in Brazil. METHODS: A cost-effectiveness simulation was conducted on the basis of a pivotal study on the use of posaconazole in acute myeloid leukemia (AML) patients, adjusting the costs to Brazilian data. RESULTS: A pharmacoeconomic analysis was performed on a hypothetical sample of 100 patients in each drug group. The total cost of posaconazole use alone was USD$ 220,656.31, whereas that for fluconazole was USD$ 83,875.00. Our results showed that patients with IFD remain hospitalized for an additional 12 days, at an average cost of USD$ 850.85 per patient per day. The total money spent by PHS for 100 patients for 100 days was USD$ 342,318.00 for the posaconazole group and USD$ 302,039.00 for the fluconazole group. An analysis of sensitivity (10%) revealed no intergroup difference. CONCLUSIONS: In Brazil posaconazole is cost-effective, and should be considered for the prophylaxis of patients with AMD/myelodysplasia (AML/MDS) undergoing chemotherapy.

Risk factors for mortality in patients with ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae.

BACKGROUND: The ideal therapeutic option for ventilator associated pneumonia caused by carbapenem-resistant Enterobacteriaceae is not defined. The aim of this study was to assess mortality-associated risk factors in patients with VAP by CRE and determine the outcome of several treatment options. METHODS: This was a retrospective study performed in two tertiary hospitals involving patients with VAP caused by CRE between January 2010 and August 2014. The outcomes were mortality within 30 days of VAP diagnosis and overall mortality during hospital admission. Risk factors for mortality were assessed by comparing variables of survivors and non-survivors. RESULTS: One hundred and twelve patients with CRE-VAP were included, 73 (65%) male, median age 56 years. The 30-day mortality was 57.1% and the overall hospital mortality was 67%. In the binary logistic regression analysis, only age >50 years was independently associated to increased mortality. Polymyxin was the most used drug (47.5%), followed by tigecycline (29.2%) and aminoglycosides (2.4%). Combined therapy with two active drugs was used by 17 patients (20.8%). No therapeutic option was independently associated to survival. However, combined therapy with two active drugs was superior to the therapy with a single active drug when inappropriate therapy was the comparator (p=0.044). The addition of carbapenem was not associated with increased survival. CONCLUSION: The best therapeutic option for VAP by CRE is still not completely defined, but the therapy with at least two active drugs was superior in this study.

Combined therapy for multi-drug-resistant Acinetobacter baumannii infection--is there evidence outside the laboratory?

Acinetobacter are among the most common bacteria isolated in hospital infections, especially in developing countries. Multi-drug, extended-drug or pan-drug resistance makes treatment a real medical challenge. In the present review, the authors describe clinical and experimental data in order to present different current and potential future strategies to treat infections caused by multi-drug-resistant Acinetobacter. The therapeutic options for carbapenem-resistant Acinetobacter are scarce, and the current options have poor pharmacokinetic aspects and several side effects. Combined therapy has been an alternative for multi-drug-resistant Acinetobacter. However, this issue is always controversial. In some studies combined therapy has shown superiority for some strains of Acinetobacter in animal models and in vitro studies. However, studies with humans are scarce and too poor quality to suggest the best approach for the treatment of infections caused by multi-drug-resistant Acinetobacter baumannii.

Molecular epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae in different facilities in Southern Brazil.

BACKGROUND: Klebsiella pneumoniae carbapenemase-producing K pneumoniae (KPC-KP) outbreaks have been reported in many countries, including Brazil. The incidence of KPC-KP infection has increased in the first semester of 2011 in Curitiba, the capital of Parana, in Southern Brazil.The aim of this study was to characterize the infections and clonal diversity of KPC-KP isolates from several institutions in Curitiba. METHODS: KPC-KP from several clinical samples and rectal swabs taken between April 2010 and July 2012 were included. One isolate per patient was evaluated. All isolates were submitted to polymerase chain reaction (PCR) for blaKPC. The genetic relatedness was evaluated using strain clustering by an automated repetitive extragenic palindromic (rep) PCR-based typing system. RESULTS: There were 641 samples that were positive for K pneumoniae carbapenemase-2 carbapenemase. There were 129 samples randomly selected for clonality evaluation. PCR and strain clustering by the automated rep PCR-based typing system identified 7 clones (A-C and E-H). Clone E was identified in only 1 hospital, and all other clones were found in >2 hospitals. Clones C and G were the most disseminated among hospitals. The infection and colonization occurred in 14 out of the 32 main hospitals in town. Similar clones were found in 2 hospitals that are administered by the same group. Another clone (H) was found in 2 hospitals receiving patients from the same municipal emergency unit. CONCLUSION: The KPC-KP outbreak in Curitiba is polyclonal, and the source is unknown. Some hospitals share the same clones.

KPC-producing Enterobacter aerogenes infection.

BACKGROUND: Enterobacter is a common nosocomial microorganism and its carbapenem's resistance has increased. The management of these cases is unclear. OBJECTIVE: We evaluated 16 patients with KPC-producing Enterobacter aerogenes infections, detailing the site of infection, therapy, clinical and epidemiological data. METHODS: A retrospective and descriptive study. Clinical data were revised and KPC-2 detection was by molecular methods. Risk factors associated with mortality were compared using appropriate tests according to variable type with a significance level of 0.05. RESULTS: The 30-day mortality rate was 37.5% with no association with inadequate treatment. Age (p=0.004) and Charlson score of comorbidities (p=0.048) were independent risk factors associated with death in the multivariate analysis. The odds ratio for age >43 years was 3.00 (95% CI: 1.02-9.32) and for Charlson score >3 was 2.00 (95% CI: 1.08-3.71). Five strains were pan-resistant based on automated susceptibility tests. All patients were treated with monotherapy. CONCLUSION: The clinician should be alert to carbapenem-resistant Enterobacteriaceae infection in older patients with comorbidities. The mortality is high and we believe that prompt and adequate therapy must be employed.

Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period.

Nonneoplastic findings in loop electrical excision procedure specimens from patients with persistent atypical squamous cells of uncertain significance in two consecutive pap smears.

The present study aimed to determine the histopathological correspondence of the diagnosis of atypical squamous cells of uncertain significance (ASCUS) in the absence of squamous intraepithelial neoplasia (SIL) in loop electrical excision procedure (LEEP) products. Retrospective histopathological analysis of 70 LEEP products preceded by ASCUS was consistently detected by two consecutive Pap smears. The presence or absence of several histopathological findings in cases with (23/70) and without (47/70) histological diagnosis of SIL were compared. Immature squamous metaplasia, severe cervicitis, and tube-endometrial metaplasia were found with similar frequency on positive and negative neoplastic disease specimens. Reactive squamous atypia, keratosis, atrophy, glandular reactive/inflammatory atypia, tunnel clusters, and microglandular hyperplasia were less frequently found in LEEP specimens presenting with SIL. Reactive squamous atypia and keratosis were consistently associated with SIL absence and appear to be responsible for the cytological diagnosis of ASCUS (P < 0.05).

A simple mathematical model to determine the ideal empirical antibiotic therapy for bacteremic patients.

BACKGROUND: Local epidemiological data are always helpful when choosing the best antibiotic regimen, but it is more complex than it seems as it may require the analysis of multiple combinations. The aim of this study was to demonstrate a simplified mathematical calculation to determine the most appropriate antibiotic combination in a scenario where monotherapy is doomed to failure. METHODS: The susceptibility pattern of 11 antibiotics from 216 positive blood cultures from January 2012 to January 2013 was analyzed based on local policy. The length of hospitalization before bacteremia and the unit (ward or intensive care unit) were the analyzed variables. Bacteremia was classified as early, intermediate or late. The antibiotics were combined according to the combination model presented herein. RESULTS: A total of 55 possible mathematical associations were found combining 2 by 2, 165 associations with 3 by 3 and 330 combinations with 4 by 4. In the intensive care unit, monotherapy never reached 80% of susceptibility. In the ward, only carbapenems covered more than 90% of early bacteremia. Only three drugs combined reached a susceptibility rate higher than 90% anywhere in the hospital. Several regimens using four drugs combined reached 100% of susceptibility. CONCLUSIONS: Association of three drugs is necessary for adequate coverage of empirical treatment of bacteremia in both the intensive care unit and the ward.