Abstract Background This study aimed to analyze the Healthcare-Associated Infections (HAI) rates and antimicrobial consumption in Intensive Care Units (ICU) in São Paulo city during the COVID-19 pandemic and compare them with the pre-pandemic period. Methods This cohort included all hospitals that reported HAI rates (Central-Line-Associated Bloodstream Infection ‒ CLABSI and Ventilator-Associated Pneumonia ‒ VAP), the proportion of microorganisms that caused CLABSI, the proportion of resistant microorganisms, and antimicrobial consumption from January 2017 ‒ December 2020. Hospitals were stratified by the number of beds, Central Venous Catheter (CVC) utilization rate, Mechanical-Ventilation (MV) utilization rate, and type of funding. Statistical analyses were based on time-series plots and regression models. Results 220 ICUs were included. The authors observed an abrupt increase in CLABSI rates after the pandemic onset. High CLABSI rates during the pandemic were associated with hospital size, funding (public and non-profit private), and low CVC use (≤ 50%). An increase in VAP rates was associated with public hospitals, and high MV use (> 35%). The susceptibility profile of microorganisms did not differ from that of the pre-pandemic period. polymyxin, glycopeptides, and antifungal use increased, especially in COVID-19 ICUs. Conclusions HAI increased during COVID-19. The microorganisms’ susceptibility profile did not change with the pandemic, but the authors observed a disproportionate increase in large-spectrum antimicrobial drug use.

ABSTRACT Naganishia albida (Cryptococcus albidus) is considered saprophytic fungi, and is rarely reported as a human pathogen. Cutaneous infections caused by non-neoformans cryptococcus are rare. We describe a case of an immunocompetent older male with cutaneous cryptococcosis caused by Naganishia albida following skin trauma, and conduct a literature review in PubMed, Lilacs, and Embase. Only six previous similar reports were found. The seven cases (including ours) were widely distributed geographically (Brazil, the US, the UK, Hungary, South Korea, and Iran), all males, and their ages varied, ranging from 14 to 86 years. Four individuals had underlying skin diseases (Sezary Syndrome, psoriasis, and skin rash without etiology) plus potentially immunosuppressive underlying conditions (diabetes mellitus, kidney transplantation, and the use of etanercept, adalimumab, and methylprednisolone). Cutaneous presentation was polymorphic, with lesions characterized as warts, ulcers, plaques, and even macules. Two patients presented disseminated disease. Serum cryptococcal antigen was negative in six patients, and diagnosis was made by fungal culture in all. There is a lack of data on optimal antifungal treatment and outcomes.

Abstract Purpose: The aim of this study was to describe the incidence and risk factors for hospital readmission and infection during the months after COVID-19 hospital admission. Methods: This prospective study included adult patients who were hospitalized due to COVID-19 and had been discharged from April 2020 to August 2020. All patients had a medical evaluation with a structured questionnaire 6 to 11 months after hospital admission. The authors included only patients with confirmed COVID-19 by RT-PCR. Patients with pregnant/postpartum women, with a proven COVID-19 reinfection or incapable of answering the questionnaire were excluded. Results: A total of 822 patients completed the follow-up assessment, and 68% reportedat least one recurrent symptom related to COVID-19. The most frequent symptom was myalgia (42%). Thirty-two percent of patients visited an emergency room after COVID-19 hospitalization, and 80 (10%) patients required re-hospitalization. Risk factors for hospital readmission were orotracheal intubation during COVID-19 hospitalization (p = 0.003, OR = 2.14), Charlson score (p = 0.002, OR = 1.21), congestive heart failure (p = 0.005, OR = 2.34), peripheral artery disease (p = 0.06, OR= 2.06) and persistent diarrhea after COVID-19 hospitalization discharge (p= 0.02, OR = 1.91). The main cause of hospital readmission was an infection, 43 (54%). Pneumonia was the most frequent infection (29%). Conclusions: The presence of symptoms after six months of COVID-19 diagnosis was frequent, and hospital readmission was relatively high. HIGHLIGHTS 32% of the patients visited an emergency room after COVID-19 hospitalization. The rate of hospital readmission after COVID-19 hospitalization is high, in the present sample 10% of patients needed a second hospitalization in 6-months Patients with persistent diarrhea after COVID-19 discharge had two times more chance to have another hospitalization in the next 6-months.

Abstract Background The relationship between Multidrug Resistant-Gram Negative Bacteria (MDR-GNB) infection and colonization in critically ill COVID-19 patients has been observed, however, it is still poorly understood. This study evaluated the risk factors for acquiring MDR-GNB in patients with severe COVID-19 in Intensive Care Units (ICU). Methods This is a nested case-control study in a cohort of 400 adult patients (≥ 18 years old) with COVID-19, hospitalized in the ICU of 4 hospitals in the city of Curitiba, Brazil. Cases were critical COVID-19 patients with one or more MDR GNB from any surveillance and/or clinical cultures were taken during their ICU stay. Controls were patients from the same units with negative cultures for MDR-GNB. Bivariate and multivariate analyses were done. Results Sixty-seven cases and 143 controls were included. Independent risk factors for MDR bacteria were: male gender (OR = 2.6; 95% CI 1.28‒5.33; p = 0.008); the hospital of admission (OR = 3.24; 95% CI 1.39‒7.57; p = 0.006); mechanical ventilation (OR = 25.7; 95% CI 7.26‒91; p < 0.0001); and desaturation on admission (OR = 2.6; 95% CI 1.27‒5.74; p = 0.009). Conclusions Male gender, desaturation, mechanical ventilation, and the hospital of admission were the independent factors associated with MDR-GNB in patients in the ICU with COVID-19. The only modifiable factor was the hospital of admission, where a newly opened hospital posed a higher risk. Therefore, coordinated actions toward a better quality of care for critically ill COVID-19 patients are essential.

OBJECTIVES: Antimicrobial stewardship programs (ASPs) comprise coordinated interventions designed to improve antimicrobial use. Understanding the current structure of ASP hospitals will support interventions for the improvement of these programs. This study aimed to describe the status of ASPs in hospitals in São Paulo, Brazil. METHODS: A cross-sectional survey was conducted on the ASPs of hospitals in the state of São Paulo from March to July 2018. Through interviews by telephone or e-mail, we queried which components of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and Centers for Disease Control and Prevention guidelines were implemented. RESULTS: The response rate was 30% (28/93 hospitals), and 26 hospitals (85%) reported having a formal ASP. The most frequently implemented strategies were antimicrobial surgical prophylaxis guidelines (100%), empiric sepsis guidelines (93%), and the presence of ASP team members during bedside rounds (96%). The least commonly implemented strategies included prior authorization for all antimicrobials (11%), pharmacokinetic monitoring, and an adjustment program for patients on IV aminoglycosides (3%). Regarding the metrics of the ASP, the most common indicator was the rate of antimicrobial resistance (77%). Eighteen hospitals evaluated antimicrobial consumption using defined daily dose, and only 29% evaluated the days of therapy; 61% of hospitals reported their results to the hospital administration and 39% to the prescribers. CONCLUSIONS: Most hospitals have a formal and active ASP, but with timely actions. We observed inconsistencies between what program leaders understand as the main objective of ASP and the metrics used to evaluate it. Part of the effort for the next few years should be to improve program evaluation metrics and to provide feedback to physicians and hospital leadership.

OBJECTIVE: This study aimed to evaluate the occurrence of coronavirus disease 2019 (COVID-19) in hemodialysis facilities and the occurrence of and risk factors for clustering of COVID-19 cases. METHODS: We conducted a cross-sectional online survey between March and July 2020, in all dialysis facilities in São Paulo state, using Google Forms. The online questionnaire contained questions addressing specific components of infection prevention and control practices and the number of cases during the COVID-19 pandemic. RESULTS: A total of 1,093 (5%) COVID-19 cases were reported among 20,984 patients; approximately 56% of the facilities had ≥1 cluster. Most facilities implemented various measures (such as allocation of dedicated COVID-19 areas/shifts, symptom screening, environmental disinfection, and maintenance of adequate ventilation) to prevent the transmission of severe acute respiratory syndrome coronavirus 2. Clustering of COVID-19 cases was suspected in only 7% of dialysis facilities. The only variable associated with this event was the performance of aerosol-generating procedures (odds ratio: 4.74; 95% confidence interval: 1.75-12.86). CONCLUSION: Attention should be paid to avoiding the performance of aerosol-generating procedures in dialysis facilities and monitoring the clustering of cases.

OBJECTIVES: Bacterial and aseptic meningitis after neurosurgery can present similar clinical signs and symptoms. The aims of this study were to develop and test a molecular method to diagnose bacterial meningitis (BM) after neurosurgery. METHODS: A 16S ribosomal RNA gene PCR-based strategy was developed using artificially inoculated cerebrospinal fluid (CSF) followed by sequencing. The method was tested using CSF samples from 43 patients who had undergone neurosurgery and were suspected to suffer from meningitis, and from 8 patients without neurosurgery or meningitis. Patients were classified into five groups, confirmed BM, probable BM, possible BM, unlikely BM, and no meningitis. RESULTS: Among the samples from the 51 patients, 21 samples (41%) were culture-negative and PCR-positive. Of these, 3 (14%) were probable BM, 4 (19%) were possible BM, 13 (62%) were unlikely BM, and 1 (5%) was meningitis negative. Enterobacterales, non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii), Staphylococcus haemolyticus, Granulicatella, Variovorax, and Enterococcus cecorum could be identified. In the group of patients with meningitis, a good agreement (3 of 4) was observed with the results of cultures, including the identification of species. CONCLUSION: Molecular methods may complement the diagnosis, guide treatment, and identify non-cultivable microorganisms. We suggest the association of methods for suspected cases of BM after neurosurgery, especially for instances in which the culture is negative.

ABSTRACT Introduction: Use of antibiotic and bacterial resistance is the result of a complex interaction not completely understood. Objectives: To evaluate the impact of entire antimicrobial use (community plus hospitals) on the incidence of bloodstream infections in intensive care units adjusted by socioeconomic factors, quality of healthcare, and access to the healthcare system. Design: Ecologic study using a hierarchical spatial model. Setting: Data obtained from 309 hospitals located in the state of São Paulo, Brazil from 2008 to 2011. Participants: Intensive care units located at participant hospitals. Outcome: Hospital acquired bloodstream infection caused by MDRO in ICU patients was our primary outcome and data were retrieved from São Paulo Health State Department. Socioeconomic and healthcare indexes data were obtained from IBGE (Brazilian Foundation in charge of national decennial census) and SEADE (São Paulo Planning and Development Department). Information on antimicrobial sales were obtained from IMS Brazil. We divided antibiotics into four different groups (1-4). Results: We observed a direct association between the use of group 1 of antibiotics and the incidences of bloodstream infections caused by MRSA (1.12; 1.04-1.20), and CR-Acinetobacter sp. (1.19; 1.10-1.29). Groups 2 and 4 were directly associated to VRE (1.72; 1.13-2.39 and 2.22; 1.62-2.98, respectively). Group 2 was inversely associated to MRSA (0.87; 0.78-0.96) and CR-Acinetobacter sp. (0.79; 0.62-0.97). Group 3 was inversely associated to Pseudomonas aeruginosa (0.69; 0.45-0.98), MRSA (0.85; 0.72-0.97) and VRE (0.48; 0.21-0.84). No association was observed for third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli. Conclusions: The association between entire antibiotic use and resistance in ICU was poor and not consistent for all combinations of antimicrobial groups and pathogens even after adjusted by socioeconomic indexes. Selective pressure exerted at the community level seemed not to affect the incidences of MDRO infection observed in intensive care setting.

ABSTRACT Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in the last decade. Increased resistance to sulfamethoxazole/trimethoprim (SMX/TMP) has been reported in S. maltophilia strains in the past few years, leading to few therapeutic options. We conducted a prospective multicenter study at two Brazilian teaching hospitals that identified S. maltophilia isolates and evaluated their antimicrobial susceptibility profile, SMX/TMP resistance genes and their clonality profile. A total of 106 non-repeated clinical samples of S. maltophilia were evaluated. Resistance to SMX/TMP was identified in 21.6% of the samples, and previous use of SMX/TMP occurred in 19 (82.6%). PCR detected the sul1 gene in 14 of 106 strains (13.2%). Of these isolates, nine displayed resistance to SMX/TMP. The resistant strains presented a polyclonal profile. This opportunistic pathogen has emerged in immunocompromised hosts, with few therapeutic options, which is aggravated by the description of emerging resistance mechanisms, although with a polyclonal distribution profile.

ABSTRACT We described 235 bloodstream infection (BSI) episodes in 146 hematopoietic stem cell transplantation (HSCT) outpatients and evaluated risk factors for hospitalization and death. Records of outpatients presenting with positive blood cultures over a 5-year period (January 2005 to December 2008) were reviewed. Variables with p< 0.1 in bivariate analysis were used in a regression logistic model. A total of 266 agents were identified, being 175 (66.7%) gram-negative, 80 (30.3%) gram-positive bacteria and 9 (3.4%) fungi. The most common underlying disease was acute leukemia 40 (27.4%), followed by lymphoma non-Hodgkin 26 (18%) and 87 patients (59.6%) were submitted to allogeneic hematopoietic stem cell transplant (HSCT). BSI episodes were more frequent during the first 100 days after transplantation (183 or 77.8%), and ninety-one (38.7%) episodes of BSI occurred up to the first 30 days. Hospitalization occurred in 26% of the episodes and death in 10% of cases. Only autologous HSCT was protector for hospitalization. Although, central venous catheter (CVC) withdrawal and the Multinational Association of Supportive Care in Cancer (MASCC) score up to 21 points were protector factors for death in the bivariate analysis, only MASCC remained as protector.

ABSTRACT Staphylococcus aureus (SA) is a commensal habitant of nasal cavities and skin. Colonization by community-acquired methicillin-resistant SA (CA-MRSA) is associated with infections in patients who have not been recently hospitalized. The aim of this study is to determine the prevalence of MRSA colonization in an outpatient population, currently unknown in Brazil. Three-hundred patients or caregivers from two teaching hospitals were included. A questionnaire was applied and nasal swabs were obtained from patients. Swabs were inoculated in brain heart infusion (BHI) with 2.5% NaCl and seeded in mannitol. Suspicious colonies were subjected to MALDI-TOF MS Microflex™ identification. Antimicrobial susceptibility test for oxacillin was performed for SA-positive samples by microdilution. Polymerase chain-reactions for detection of mecA and coA genes were performed for resistant samples. Data about MRSA carriers were compared with non-carriers. There were 127 S. aureus isolates, confirmed by MALDI-TOF. Only seven (2.3%) were MRSA and positive for mecA and coA genes. Factors associated with MRSA carriage were African ethnicity, skin diseases or antibiotic use. The majority of them were from Dermatology clinics. Prevalence of MRSA colonization in individuals from the community was low in our study (2.3%). This finding raises the hypothesis of inter-household transmission of SA, although we did not find any association between MRSA-colonization and the shared use of personal objects. Given the low prevalence of MRSA carriers observed, empirical antimicrobial coverage for MRSA in community-acquired infections should be not necessary.

O objetivo foi descrever um surto de infecções da corrente sanguínea por complexo B. cepacia (Bcc) nos ambulatórios de hematologia e transplante de medula óssea. Métodos: Em 15/02/2008, um surto de Bcc foi suspeitado. 24 casos foram identificados. Os dados demográficos e clínicos foram avaliados. Mãos de profissionais da saúde e ambiente foram cultivadas. Espécies foram determinadas e tipadas. Reforço da higiene das mãos, cuidados com cateteres, terapia de infusão e manutenção da câmara de fluxo laminar foram realizadas. 16 profissionais de saúde (PS) diferentes manipularam os cateteres. Heparina multidoses e soro eram preparadas em um balcão comum a ambas as unidades. Resultados: 14 pacientes tiveram B. multivorans(um paciente teve também B. cenopacia), 6 Bcc não-multivorans e um teve um agente não pertencente a Bcc. Clone A de B. multivorans ocorreu em 12 pacientes (da Hematologia), em 10 o cateter havia sido utilizado nos dias 11 ou 12 de fevereiro. Culturas ambientais e de PS foram negativos. Todos os pacientes foram tratados com meropenem e selo de ceftazidima. Oito pacientes (30%) foram hospitalizados. Não ocorreram mortes. Após as medidas de controle, nenhum novo caso ocorreu. Conclusões: Este surto policlonal pode ser explicado por uma fonte comum contendo várias espécies de Bcc, talvez a câmara de fluxo laminar comum a ambas as unidades. Pode ter havido contaminação por B. multivorans (clone A) de frascos multi-dose.

Aim: The objective was to describe an outbreak of bloodstream infections by Burkholderia cepacia complex (Bcc) in bone marrow transplant and hematology outpatients.Methods: On February 15, 2008 a Bcc outbreak was suspected. 24 cases were identified. Demographic and clinical data were evaluated. Environment and healthcare workers' (HCW) hands were cultured. Species were determined and typed. Reinforcement of hand hygiene, central venous catheter (CVC) care, infusion therapy, and maintenance of laminar flow cabinet were undertaken. 16 different HCWs had cared for the CVCs. Multi-dose heparin and saline were prepared on counter common to both units.Findings: 14 patients had B. multivorans(one patient had also B. cenopacia), six non-multivorans Bcc and one did not belong to Bcc. Clone A B. multivorans occurred in 12 patients (from Hematology); in 10 their CVC had been used on February 11/12. Environmental and HCW cultures were negative. All patients were treated with meropenem, and ceftazidime lock-therapy. Eight patients (30%) were hospitalized. No deaths occurred. After control measures (multidose vial for single patient; CVC lock with ceftazidime; cleaning of laminar flow cabinet; hand hygiene improvement; use of cabinet to store prepared medication), no new cases occurred.Conclusions: This polyclonal outbreak may be explained by a common source containing multiple species of Bcc, maybe the laminar flow cabinet common to both units. There may have been contamination by B. multivorans (clone A) of multi-dose vials.

RESUMOS. maltophilia contem um novo gene qnr cromossômico denominado Smqnr que contribui para baixa resistência intrínseca a quinolonas. Descrevemos Smqnr em 13 isolados clínicos de S. maltophilia de dois hospitais brasileiros, ao longo do período de dois anos. Os isolados foram identificados pela API 20 NE (bioMérieux, França). Susceptibilidade pelo método de microdiluição dos seguintes antibióticos trimetroprim/sulfametoxazol, ciprofloxacina, levofloxacina, minociclina, ceftazidima, cloranfenicol e ticarcilina/clavulanato foi realizada segundo o CLSI. Detecção do gene de Smqnr foi realizada por PCR. A sequência de Smqnr foi comparada com aquelas depositadas no GenBank. Foi realizada eletroforese em gel de campo pulsado (PFGE) de todos os isolados. Treze isolados contendo Smqnr foram sequenciados e identificados três variantes do gene Smqnr. Todos os 13 isolados de Smqnr apresentaram diferentes padrões por PFGE. Este é o primeiro relato de Smqnr em isolados de S. maltophilia no Brasil.

SUMMARYStenotrophomonas maltophilia contains a novel chromosomally-encoded qnr gene named Smqnr that contributes to low intrinsic resistance to quinolone. We described Smqnr in 13 clinical isolates of S. maltophilia from two Brazilian hospitals, over a 2-year period. The strains were identified by API 20 NE (bioMérieux, France). Susceptibility by microdilution method to trimetroprim/sulfamethoxazole, ciprofloxacin, levofloxacin, minocycline, ceftazidime, chloramphenicol and ticarcillin/clavulanate was performed according to CLSI. PCR detection of Smqnr gene was carried out. The sequence of Smqnr was compared with those deposited in GenBank. Pulsed-field gel electrophoresis (PFGE) of all strains was performed. Thirteen Smqnr positives isolates were sequenced and three novel variants of Smqnr were identified. All 13 Smqnr isolates had distinguishable patterns by PFGE. This is the first report of Smqnr in S. maltophilia isolated in Brazil.

OBJECTIVE: The objective of this study was to evaluate whether the outcomes of carbapenem-resistant Acinetobacter infections treated with ampicillin/sulbactam were associated with the in vitro susceptibility profiles. METHODS: Twenty-two infections were treated with ampicillin/sulbactam. The median treatment duration was 14 days (range: 3-19 days), and the median daily dose was 9 g (range: 1.5-12 g). The median time between Acinetobacter isolation and treatment was 4 days (range: 0-11 days). RESULTS: The sulbactam minimal inhibitory concentration (MIC) ranged from 2.0 to 32.0 mg/L, and the MIC was not associated with patient outcome, as 4 of 5 (80%) patients with a resistant infection (MIC≥16), 5 of 10 (50%) patients with intermediate isolates (MIC of 8) and only 1 of 7 (14%) patients with susceptible isolates (MIC ≤4) survived hospitalization. CONCLUSION: These findings highlight the need to improve the correlation between in vitro susceptibility tests and clinical outcome.

This report describes a survey of microbiology laboratories (n = 467) serving Brazilian hospitals with >10 intensive care beds and/or involved in the government health care adverse event reporting system. Coordinators were interviewed and laboratories classified as follows: Level 0 (no minimal functioning conditions-85.4% of laboratories); Level 1 (minimal functioning conditions but inadequate execution of basic routine-6.7%); Level 2 (minimal functioning conditions and adequate execution of basic routine but no adequate procedures for quality control-5.8%); Level 3 (minimal functioning conditions, adequate execution of basic routine, and adequate procedures for quality control, but no direct communication with the infection control department-0.9%); Level 4 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, and direct communication with infection control, but no available advanced resources-none); and Level 5 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, direct communication with infection control, and available advanced resources-0.9%). Twelve laboratories did not perform Ziehl-Neelsen staining; 271 did not have safety cabinets; and >30% without safety cabinets had automated systems. Low quality was associated with serving hospitals not participating in government adverse-event program; private hospitals; nonteaching hospitals; and those outside state capitals. Results may reflect what occurs in many other countries where defining priorities is important due to limited resources.

Este artículo describe una encuesta realizada en Brasil en laboratorios de microbiología (n = 467) que prestaban servicio a hospitales que contaban al menos con 10 camas de cuidados intensivos. Se entrevistó a los coordinadores y los laboratorios se clasificaron de la siguiente manera: nivel 0 (sin condiciones de funcionamiento mínimas: 85,4% de los laboratorios), nivel 1 (condiciones de funcionamiento mínimas pero ejecución inadecuada del trabajo habitual básico: 6,7%), nivel 2 (condiciones de funcionamiento mínimas y ejecución adecuada del trabajo habitual básico, pero sin procedimientos de control de calidad apropiados: 5,8%), nivel 3 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico y procedimientos de control de calidad apropiados, pero sin comunicación directa con el departamento de control de infecciones: 0,9%), nivel 4 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico, procedimientos de control de calidad apropiados y comunicación directa con el departamento de control de infecciones, pero sin recursos avanzados disponibles: ningún laboratorio) y nivel 5 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico, procedimientos de control de calidad apropiados, comunicación directa con el departamento de control de infecciones y recursos avanzados disponibles: 0,9%). Doce laboratorios no realizaban la tinción de Ziehl-Neelsen, 271 no contaban con cámaras de seguridad biológica, y más de 30% de los laboratorios que carecían de cámaras de seguridad biológica tenían sistemas automatizados. La escasa calidad se asoció a la falta de participación en el programa gubernamental de notificación de acontecimientos adversos, a los hospitales privados, a los hospitales no docentes y a la ubicación de los hospitales fuera de las capitales de los estados. Los resultados pueden reflejar lo que ocurre en muchos otros países con recursos limitados, donde es importante definir las prioridades.