Healthcare-associated infections: a threat to the survival of patients with COVID-19 in intensive care units.

BACKGROUND: Wide variation in mortality rates among critically ill patients with coronavirus disease 2019 (COVID-19) has been reported. This study evaluated whether healthcare-associated infections (HAI) are a risk factor for death among patients with severe COVID-19 in the intensive care unit (ICU). METHODS: This retrospective cohort study included patients with severe COVID-19 hospitalized in the ICU of four hospitals in the city of Curitiba, Brazil. Patients with COVID-19 who died during ICU hospitalization were compared with those who were discharged. A second analysis compared patients who developed HAI in the ICU with those who did not. Multiple logistic regression models were used to control for confounders. RESULTS: In total, 400 patients were included, and 123 (31%) patients developed HAI. The most common HAI was lower respiratory tract infection (67%). Independent risk factors for death were: age [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.43-2.15; P<0.0001]; clinical severity score (OR 2.21, 95% CI 1.70-2.87; P<0.0001); renal replacement therapy (OR 12.8, 95% CI 5.78-28.6; P<0.0001); and HAI (OR 5.9, 95% CI 3.31-10.5; P<0.0001). A longer interval between symptom onset and hospital admission was protective against death (OR 0.93, 95% CI 0.88-0.98; P=0.017). The only independent factors associated with HAI were high C-reactive protein and low PaO2/FiO2 ratio. CONCLUSIONS: No factors that could point to a high-risk group for HAI acquisition were identified. However, age, dialysis and HAI increased the risk of death in ICU patients with severe COVID-19; of these, HAI is the only preventable risk factor.

Nationwide surveillance system to evaluate hospital-acquired COVID-19 in Brazilian hospitals.

BACKGROUND: Although the risk of SARS-CoV-2 transmission within hospitals has been well recognized, there is a paucity of data on its occurrence. Our aim was to report the incidence of hospital-acquired (HA) COVID-19 at Brazilian hospitals. METHODS: We investigated the incidence of HA COVID-19 in Brazilian hospitals using data from a national surveillance system, from August 2020 through September 2021. Definitions of HA COVID-19 were: (1) symptom onset >14 days after hospital admission plus a positive SARS-CoV-2 RNA or antigen test; (2) symptom onset on days 8-14 after admission, plus a positive SARS-CoV-2 RNA or antigen test positive, plus documented high-risk exposure. We performed descriptive analyses and reported HA COVID-19 rates using pooled mean and percentile distribution. RESULTS: A total of 48,634 cases of HA COVID-19 were reported from 1428 hospitals. Incidence ranged from 0.16/1000 patient-days at neonatal intensive care units (ICUs) to 5.8/1000 patient-days at adult ICUs. The highest incidence of HA COVID-19 was during the months March to July 2021, similar to that which was observed for community-acquired COVID-19. CONCLUSIONS: This report provides a national view of the burden of HA COVID-19. The highest incidence of HA COVID-19 similar that which was observed for community-acquired COVID-19. We believe that this reflects the difficulty of implementing preventive measures. Further studies evaluating risk factors for the hospital transmission of SARS-Cov-2 should clarify strategies to minimize the risk of HA COVID-19 and may be applicable to other respiratory diseases. Furthermore, the implementation of a national system to evaluate HA COVID-19 has the potential to shine a light on this problem and lead to interventions in each hospital.

Implementation of tailored interventions in a statewide programme to reduce central line-associated bloodstream infections.

BACKGROUND: There have been few studies exploring implementation strategies to central line-associated bloodstream infections (CLABSIs) in low- or middle-income countries. AIM: To implement tailored interventions to reduce CLABSI rates in adult intensive care units. METHODS: The implementation strategy of the State Health Department was performed in São Paulo State, Brazil, over two cycles. Cycle 1 (56 hospitals) was exploratory and cycle 2 (77 hospitals) was designed to confirm the hypothesis generated by the first cycle, with three phases each (pre-intervention, intervention, post-intervention). Cycles included: evaluation of healthcare workers' knowledge, observation of practices, and CLABSI rates monthly report. In cycle 1, a log-normal mixed model was used to select variables significantly associated with the reduction of CLABSI. In cycle 2, CLABSI rates were evaluated. FINDINGS: Healthcare workers' practices improved after intervention. In cycle 1, reduction of CLABSI rates was more pronounced in hospitals with initial CLABSI rates >7.4 per 1000 catheter-days (P < 0.001) and those that introduced the use of peripherally inserted central catheters (P = 0.01). For hospitals with high CLABSI initial rates, simulation demonstrated that the rates were expected to decrease by 36% (95% CI: 9-63), no matter the type of intervention. In cycle 2, there was an overall decrease in CLABSI rates during the intervention period; whereas the mean rate fell further post-intervention, rates at the 90th percentile increased. CONCLUSION: The implementation strategy may have had an effect on infection rates independently of the specific interventions implemented; however, the sustainability of reduction in the post-intervention period remains a challenge.

Ceftriaxone versus ceftriaxone plus a macrolide for community-acquired pneumonia in hospitalized patients with HIV/AIDS: a randomized controlled trial

OBJECTIVES: To evaluate if treatment with ceftriaxone and a macrolide, improved patient outcome when compared with monotherapy with ceftriaxone, in hospitalized patients with human immunodeficiency virus/acquired immunodeficient syndrome (HIV/AIDS) with community-acquired pneumonia (CAP). METHODS: Adult patients with HIV hospitalized due to suspected CAP were randomized to receive one of two regimens, ceftriaxone plus macrolide or ceftriaxone plus placebo, at a 1:1 proportion (Brazilian Clinical Trials Registry: RBR-8wtq2b). The primary outcome was in-hospital mortality and the secondary outcomes were mortality within 14 days, need for vasoactive drugs, need for mechanical ventilation, time to clinical stability and length of hospitalization. RESULTS: A total of 227 patients were randomized, two were excluded after randomization; 225 patients were analysed (112 receiving ceftriaxone plus placebo and 113 receiving ceftriaxone plus macrolide). The frequency of the primary outcome, in-hospital mortality, was not statistically different between the regimens: 12/112 (11%) patients who received ceftriaxone plus placebo and 17/113 (15%) who received ceftriaxone plus macrolide died during hospitalization (hazard ratio 1.22, 95% CI 0.57-2.59). We did not find differences between the regimens for any of the secondary outcomes, including mortality within 14 days, which occurred in 5/112 (4%) patients with ceftriaxone plus placebo and in 12/113 (11%) patients with ceftriaxone plus macrolide (relative risk 2.38, 95% CI 0.87-6.53) CONCLUSIONS: Among hospitalized patients with HIV/AIDS with CAP, treatment with ceftriaxone and a macrolide did not improve patient outcomes, when compared with ceftriaxone monotherapy

Ceftriaxone versus ceftriaxone plus a macrolide for community-acquired pneumonia in hospitalized patients with HIV/AIDS: a randomized controlled trial.

OBJECTIVES: To evaluate if treatment with ceftriaxone and a macrolide, improved patient outcome when compared with monotherapy with ceftriaxone, in hospitalized patients with human immunodeficiency virus/acquired immunodeficient syndrome (HIV/AIDS) with community-acquired pneumonia (CAP). METHODS: Adult patients with HIV hospitalized due to suspected CAP were randomized to receive one of two regimens, ceftriaxone plus macrolide or ceftriaxone plus placebo, at a 1:1 proportion (Brazilian Clinical Trials Registry: RBR-8wtq2b). The primary outcome was in-hospital mortality and the secondary outcomes were mortality within 14 days, need for vasoactive drugs, need for mechanical ventilation, time to clinical stability and length of hospitalization. RESULTS: A total of 227 patients were randomized, two were excluded after randomization; 225 patients were analysed (112 receiving ceftriaxone plus placebo and 113 receiving ceftriaxone plus macrolide). The frequency of the primary outcome, in-hospital mortality, was not statistically different between the regimens: 12/112 (11%) patients who received ceftriaxone plus placebo and 17/113 (15%) who received ceftriaxone plus macrolide died during hospitalization (hazard ratio 1.22, 95% CI 0.57-2.59). We did not find differences between the regimens for any of the secondary outcomes, including mortality within 14 days, which occurred in 5/112 (4%) patients with ceftriaxone plus placebo and in 12/113 (11%) patients with ceftriaxone plus macrolide (relative risk 2.38, 95% CI 0.87-6.53). CONCLUSIONS: Among hospitalized patients with HIV/AIDS with CAP, treatment with ceftriaxone and a macrolide did not improve patient outcomes, when compared with ceftriaxone monotherapy.

Vancomycin-resistant enterococci isolates colonizing and infecting haematology patients: clonality, and virulence and resistance profile.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are an important agent of colonization and infection in haematology patients. However, the role of virulence on VRE colonization and infection is controversial. AIM: To characterize the lineage, virulence and resistance profile of VRE infection and colonization isolates; as well as their impact on outcome of haematology patients using a regression logistic model. METHODS: Eighty-six isolates (80 Enterococcus faecium and six E. faecalis) from 76 patients were evaluated. Polymerase chain reaction for resistance and virulence genes, and pulsed-field gel electrophoresis and whole genome sequencing of the major clusters, were performed. Bivariate and multivariate analyses were carried out to evaluate the role of virulence genes on outcome. FINDINGS: All isolates harboured the vanA gene. Regarding the virulence genes, 96.5% of isolates were positive for esp, 69.8% for gelE and asa1 genes. VRE infection isolates were more virulent than colonization isolates and harboured more often the gelE gene (P = 0.008). Infections caused by VRE carrying asa1 gene resulted more frequently in death (P = 0.004), but only the predominant clone remained as protector in the multivariate model. The E. faecium strains were assigned to seven STs (ST78, ST412, ST478, ST792, ST896, ST987, ST963) that belonged to CC17. The E. faecalis sequenced belonged to ST9 (CC9). CONCLUSION: E. faecium was predominant, and infection isolates were more virulent than colonization isolates and harboured more often the gene gelE. Infections caused by VRE carrying the asa1 gene appeared to be associated with a fatal outcome.

Carbapenem-resistant Enterobacteriaceae in patients admitted to the emergency department: prevalence, risk factors, and acquisition rate.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) have been reported worldwide and are associated with high mortality rates. Intestinal colonization acts as a reservoir and fosters exchange of resistance mechanisms. AIM: To investigate the prevalence of patients harbouring CRE on hospital admission, risk factors associated, and the acquisition rate within the emergency department (ED). METHODS: This was a cross-sectional survey with 676 patients consecutively admitted to the ED study during the months of May to July 2016. A questionnaire was performed and rectal swabs were collected from patients on admission, for culture and for multiplex real-time polymerase chain reaction (PCR). If the patient was hospitalized for more than one week in the ED, samples were taken again to determine the acquisition rate of CRE. FINDINGS: Forty-six patients were colonized; all positive PCR were Klebsiella pneumoniae carbapenemase. The acquisition rate was 18%. Previous exposure to healthcare in the last year, liver disease, and use of antibiotics in the last month were risk factors for colonization. Six patients with no previous exposure to healthcare were CRE-colonized on admission, suggesting transmission of CRE within the community. CONCLUSION: Screening of high-risk patients on admission to the ED is a strategy to early identify CRE carriage and may contribute to control CRE dissemination.

Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia.

This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site.

Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins.

Treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae infections (KPC-EI) remains a challenge. Combined therapy has been proposed as the best choice, but there are no clear data showing which combination therapy is superior. Our aim was to evaluate the effectiveness of antimicrobial regimens for treating KPC-EI. This was a retrospective cohort study of KPC-EI nosocomial infections (based on CDC criteria) between October 2009 and June 2013 at three tertiary Brazilian hospitals. The primary outcomes were the 30-day mortality for all infections and the 30-day mortality for patients with bacteraemia. Risk factors for mortality were evaluated by comparing clinical variables of survivors and nonsurvivors. In this study, 118 patients were included, of whom 78 had bacteraemia. Catheter-related bloodstream infections were the most frequent (43%), followed by urinary tract infections (n = 27, 23%). Monotherapy was used in 57 patients and combined treatment in 61 patients. The most common therapeutic combination was polymyxin plus carbapenem 20 (33%). Multivariate analysis for all infections (n = 118) and for bacteremic infections (n = 78) revealed that renal failure at the end of treatment, use of polymyxin and older age were prognostic factors for mortality. In conclusion, polymyxins showed suboptimal efficacy and combination therapy was not superior to monotherapy.

Risk factor for death in hematopoietic stem cell transplantation: are biomarkers useful to foresee the prognosis in this population of patients?

BACKGROUND: The morbidity and mortality in hematopoietic stem cell transplantation (HSCT) occur due to infectious complications and constitute the major clinical problems in HSCT recipients. The role of the use of biomarkers in post-HSCT patients is still controversial. OBJECTIVES: To assess the serum values of biomarkers interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) and risk factors for post-HSCT death. PATIENTS AND METHODS: Prospective study conducted in patients submitted to HSCT at a university hospital. Biomarkers (IL-6, PCT and CRP) were assessed on the day afebrile neutropenia was detected, in the febrile event, 24 and 72 h after fever onset and 48 h or 5 days if fever persisted. Patients were compared as to the death outcome within 30 days from the HSCT. Variables with p < 0.15 were included in the multivariate analysis model (MVA) that were performed for all patients included in the study and separated for autologous and allogeneic HSCT patients. RESULTS: 296 patients with ages ranging between 15 and 70 years, neutropenic, submitted to HSCT, being 216 (73%) autologous and 80 (20%) allogeneic were assessed. One hundred and ninety (64.2%) patients presented fever after the transplantation and infection microbiologically controlled in 78 (26.4%). Twenty-three cases (7.8%) evolved to death. The risk factors associated with death in the bivariate analysis were age, allogeneic transplantation, unrelated transplantation, GVHD, bloodstream infection by Gram-negative, IL-6 >140 pg/mL and CRP ≥ 120 mg/L and the protective ones were lymphoma and hospital outpatient support. The independent variables in the MVA associated with death were allogeneic and unrelated transplantation, blood stream infection (BSI) by Gram-negative, LDH ≥ 390 UI/L, urea ≥ 25 mg/dL and CRP ≥ 120 mg/L for HSCT transplanted patients and BSI due to Gram-negative and CRP ≥ 120 mg/L for allogeneic HSCT, however, CRP ≥ 120 mg/L did not remain in the model when urea ≥ 25 mg/L was included. No independent risk factor was found for autologous patients. CONCLUSIONS: Out of the biomarkers assessed, only CRP ≥ 120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH ≥ 390 UI/L and urea ≥ 25 mg/dL. For allogeneic patients only CRP ≥ 120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea ≥ 25 mg/L was included.

Trauma is associated with a better prognosis in intensive care patients with Acinetobacter infections.

PURPOSE: Acinetobacter baumannii has emerged as a common cause of infection in war-related trauma, civilian trauma and other surgical emergencies. The aim of this study was to determine prognostic factors especially trauma, in critically ill surgical patients with Acinetobacter spp. infection in a reference emergency ICU. METHODS: A retrospective review of medical records was conducted for all patients admitted to the ICU who developed Acinetobacter spp. infection from January 2007 to December 2009. Bivariate and multivariate analyses were made for 36 patients. The end-point analyzed was the in-hospital mortality. RESULTS: The initial analysis revealed a majority of young (43.6 years ± 17.1) men (92 %), trauma victims (78 %) and an in-hospital mortality of 30 %. Patients who had not suffered trauma presented with other surgical conditions and were on average older than trauma patients (57 ± 12 versus 40 ± 16 years). The overall APACHE II score average was 15.3. The ventilator-associated pneumonia was the main Acinetobacter infection diagnosed. In bivariate analysis lower Glasgow coma scale (p = 0.01) was associated with increased chance of death and being victim of trauma was a protecting factor (OR: 0.16; 95 % CI: 0.03-0.89). Receiving adequate treatment made no difference to outcome (OR: 0.55; 95 % CI: 0.05-3.15). Multivariate analysis showed that only the presence of trauma was independently associated with prognosis and was a protecting factor. CONCLUSION: Trauma was a marker of good prognosis in emergency ICU patients with Acinetobacter spp. infection.

Susceptibility of multiresistant gram-negative bacteria to fosfomycin and performance of different susceptibility testing methods.

Fosfomycin may be a treatment option for multiresistant Gram-negative bacteria. This study compared susceptibility methods using 94 multiresistant clinical isolates. With agar dilution (AD), susceptibilities were 81%, 7%, 96%, and 100% (CLSI) and 0%, 0%, 96%, and 30% (EUCAST), respectively, for Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter spp. Categorical agreement between Etest and AD for Enterobacteriaceae and A. baumannii was ≥80%. Disk diffusion was adequate only for Enterobacter. CLSI criteria for urine may be adequate for systemic infections.

An outbreak of respiratory syncytial virus infection in hematopoietic stem cell transplantation outpatients: good outcome without specific antiviral treatment.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in hematopoietic stem cell transplantations (HSCT) patients. The efficacy of treatment, however, remains controversial. We describe an outbreak of 31 cases of RSV that occurred in an HSCT outpatient care unit in the fall season from March through May 2010, with a good outcome without any specific antiviral treatment. METHODS: During these 3 months, 222 nasal wash samples were tested and, of these, 31 outpatients were positive for RSV. In 2009, 99 samples had been tested and only 10 outpatients were positive for RSV in the same period. RESULTS: Seven (22.5%) patients had severe neutropenia (<500 cells/µL); severe lymphopenia (<200 cells/µL) was present in 13 (41.9%) patients, and 14 (45%) had received intravenous broad-spectrum antibiotics. Hospitalization was necessary only for 8 patients (25.8%); 20 had lower respiratory tract infection (64.5%). Only 1 patient died as a result of proven invasive aspergillosis. CONCLUSION: This report suggests that HSCT outpatients with no risk factors may not always require specific treatment for RSV.

Nosocomial outbreak of Pantoea agglomerans bacteraemia associated with contaminated anticoagulant citrate dextrose solution: new name, old bug?

We describe an outbreak investigation of Pantoea agglomerans bacteraemia associated with anticoagulant citrate-dextrose 46% (ACD) solution prepared in-house. A healthy man presented with septic shock during plasmapheresis for granulocyte donation. The solution used for priming and blood samples were sent for culture. Identification of the isolate to species level was performed by gyrB sequencing. Typing was performed by pulsed-field gel electrophoresis (PFGE). In total, eight cases were identified during a three-week period. P. agglomerans was also cultured from six ACD solution bags. Isolates from patients and ACD bags were identical by PFGE. All isolates were susceptible to ampicillin, cephazolin, gentamicin, ciprofloxacin, cefepime and imipenem.

Randomized study of surgical prophylaxis in immunocompromised hosts.

Although prophylaxis is current practice, there are no randomized controlled studies evaluating preoperative antimicrobial prophylaxis in dental procedures in patients immunocompromised by chemotherapy or organ transplants. To evaluate prophylaxis in dental-invasive procedures in patients with cancer or solid organ transplants, 414 patients were randomized to receive one oral 500-mg dose 2 hours before the procedure (1-dose group) or a 500-mg dose 2 hours before the procedure and an additional dose 8 hours later (2-dose group). Procedures were exodontia or periodontal scaling/root planing. Follow-up was 4 weeks. No deaths or surgical site infections occurred. Six patients (1.4%) presented with use of pain medication > 3 days or hospitalization during follow-up: 4 of 207 (2%) in the 1-dose group and 2 of 207 (1%) in the 2-dose group (relative risk, 2.02; 95% confidence interval, 0.37-11.15). In conclusion, no statistically significant difference occurred in outcome using 1 or 2 doses of prophylactic amoxicillin for invasive dental procedures in immunocompromised patients.

Candida colonisation as a source for candidaemia.

Candida spp. are important healthcare-associated pathogens. Identifying the source of infection is important for prevention and control strategies. The objective of this study was to evaluate candida colonisation sites as potential sources for candidaemia. Sixty-three consecutive patients with a positive blood culture for candida were included. Surveillance cultures were collected from urine, rectum, oropharynx, skin, intravascular catheter tip and skin around catheter. Molecular typing was performed when the same species of candida was isolated from blood and surveillance sites of a patient. C. albicans was associated with 42% of candidaemias, C. parapsilosis 33%, C. tropicalis 16% and C. guilliermondii, C. krusei, C. glabrata, C. holmii and C. metapsilosis were all 2% each. Six of 10 C. parapsilosis catheter tip isolates were indistinguishable from corresponding blood isolates (all in neonates). C. albicans isolates from blood were indistinguishable from corresponding gastrointestinal tract isolates in 13 of 26 patients and from catheter tip isolates in two patients. In conclusion, the results suggest that gastrointestinal colonisation is the probable source of C. albicans candidaemia and C. parapsilosis is exogenous.

Investigation of an outbreak of Enterobacter cloacae in a neonatal unit and review of the literature.

Enterobacter cloacae has emerged as an important pathogen in neonatal units, with several outbreaks of infection being reported. The aim of this study was to investigate an outbreak of sepsis due to E. cloacae in a neonatal unit and to review the literature. A retrospective cohort study was conducted in which cases were compared with all newborns hospitalised for more than 48h in the neonatal intensive care unit (NICU). Cohorting of infected patients and work reorganisation were implemented. Pulsed-field gel electrophoresis was performed. The retrospective cohort included the six cases and 13 control patients that had been in the NICU during April 2006. Univariate analysis showed that the use of dobutamine was significantly associated with infection (P=0.036) and that enteral feeding was a protective factor (P=0.02). Multivariate analysis did not find any independent risk factor. Bed occupancy rate in March 2006 was 109.6%, indicating overcrowding. PFGE identified indistinguishable patterns among isolates from all six newborns. PubMed and OVID was search from 1 January 1983 to 15 January 2008 for papers including the terms 'E. cloacae', 'outbreaks', 'clusters' in combination with 'neonate', 'newborn', and 'infant'. We found 26 reports of outbreaks due to E. cloacae in neonate patients: sixteen (52%) were bloodstream infection outbreaks, of which two (12.5%) were related to multiple-dose medications. The source for our outbreak was not identified. Reinforcement of hygiene practices, restrictions on new admissions and the establishment of single-dose medications helped to control the outbreak.