Subnotificação de desfechos desfavoráveis da sífilis congênita no Sistema de Informação de Agravos de Notificação no estado de São Paulo, 2007-2018 / Underreporting of unfavorable outcomes of congenital syphilis on the Notifiable Health Conditions Information System in the state of São Paulo, Brazil, 2007-2018 / Subnotificación de resultados desfavorables de sífilis congénita en el Sistema de Información de Enfermedades de Declaración Obligatoria en el estado de São Paulo, Brasil, 2007-2018

Objetivo: descrever a frequência de subnotificação de desfechos desfavoráveis da sífilis congênita no estado de São Paulo, Brasil, 2007-2018. Métodos: estudo descritivo dos casos de aborto, óbitos fetais e não fetais por sífilis congênita notificados no Sistema de Informação de Agravos de Notificação (Sinan), e daqueles registrados com sífilis congênita, em qualquer linha da Declaração de Óbito, no Sistema de Informações sobre Mortalidade (SIM), mediante relacionamentos probabilístico e determinístico. Resultados: dos 27.713 casos de sífilis congênita notificados, 1.320 evoluíram para óbito (871 fetais, 449 infantis) e foram pareados com o SIM; 355 óbitos (259 fetais, 96 infantis) não constavam no Sinan; ocorreu incremento de desfechos desfavoráveis, de 11,4% para óbitos infantis por sífilis congênita, 3,0% para óbitos fetais e 1,9% para abortos. Conclusão: o emprego de diferentes técnicas de relacionamento mostrou-se adequado para identificar a frequência da subnotificação dos desfechos desfavoráveis da sífilis congênita no estado de São Paulo.

Objective: to describe the frequency of underreporting of unfavorable outcomes of congenital syphilis in the state of São Paulo, Brazil, 2007-2018. Methods: this was a descriptive study of cases of abortion, fetal and non-fetal deaths due to congenital syphilis reported on the Notifiable Health Conditions Information System (Sistema de Informação de Agravos de Notificação - SINAN), and those of congenital syphilis registered in any line in the Death Certificate, on the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM), by means of probabilistic and deterministic linkage. Results: of the 27,713 cases of congenital syphilis reported, 1,320 progressed to death (871 fetal deaths, 449 infant deaths) and were matched to the SIM; 355 deaths (259 fetal deaths, 96 infant deaths) were not included on SINAN; there was an increase in unfavorable outcomes,11.4% for infant deaths due to congenital syphilis, 3.0% for fetal deaths and 1.9% for abortions. Conclusion: the use of different relationship techniques proved to be adequate to identify the frequency of underreporting of unfavorable outcomes of congenital syphilis in the state of São Paulo.

Objetivo: describir la frecuencia de la subnotificación de resultados desfavorables por sífilis congénita en el estado de São Paulo, de 2007 a 2018. Métodos: estudio descriptivo de los casos de aborto espontáneo, muertes fetales y no fetales por sífilis congénita notificados en la Información Sistema de Enfermedades de Declaración Obligatoria (Sinan), y las registradas con sífilis congénita en el Sistema de Información de Mortalidad (SIM) mediante relaciones probabilísticas y determinísticas. Resultados: de los 27.713 casos de sífilis congénita, fallecieron 1.320 (871 fetales, 449 infantiles) y se emparejaron con SIM; 355 muertes (259 fetales, 96 infantiles) no se incluyeron en Sinan. Hubo un aumento en los resultados desfavorables: 11,4% muertes infantiles por sífilis congénita; 3,0% muertes fetales y 1,9% abortos. Conclusión: el uso de diferentes técnicas de vinculación demostró ser adecuado para identificar la frecuencia de subregistro de resultados desfavorables de sífilis congénita en el estado de São Paulo.

NDM-producing Enterobacterales prevalence associated to COVID-19 in a tertiary hospital

Abstract Colonizations/Infections caused by carbapenem-resistant Enterobacterales are of great clinical and epidemiological importance due to their rapid dissemination and high mortality rates. In this scenario, the use of antibiotics intensified by the COVID-19 pandemic has brought about a great warning on the real impact that this pandemic could have on antimicrobial management programs and long-term antimicrobial resistance rates. The objective of this study was to evaluate the increase of New Delhi Metallo β-Lactamase (NDM)-producing Enterobacterales cases in COVID-19 units of a complex Brazilian tertiary hospital. This retrospective observational study included all patients admitted to the hospital identified as colonized or infected by NDM-producing Gram negative bacilli (GNB), from January 2017 to April 2021. Forty-two NDM-producing Enterobacterales were identified in 39 patients. The rate of NDM cases per total surveillance cultures increased progressively between 2017 and 2021 (chi-2 for trend, p < 0.0001) and was associated with a higher occurrence specifically in COVID units (Fisher exact, p < 0.0001). The molecular investigation of the NDM-producing Klebsiella pneumoniae strains revealed the emergence of diverse clones during the COVID-19 period, also with possible evidence of horizontal transmission among patients within COVID units. NDM-producing Enterobacterales with multiple and different clonalities in the COVID-19 units also raised questions about the importance of other factors besides horizontal clonal transfer, including the increase of antimicrobial consumption by these patients.

Case report of a child with influenza and fatal community-associated methicillin-resistant Staphylococcus aureus sepsis

Abstract In the present study, we report the incidence of septic shock syndrome associated with methicillin-resistant Staphylococcus aureus in a child who initially presented influenza-like illness and developed septic shock shortly after 48 h of hospitalization, and eventually died within a few hours of the onset of sepsis. S. aureus isolated from the blood culture was characterized as the community-associated strain carrying the staphylococcal cassette chromosome mec (SCCmec) type IV element. Therefore, it is important to better understand the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections and their potential association with influenza for early diagnosis and successful treatment of this fatal disease.

Effect of polymyxin B-containing regimens on renal function for the treatment of carbapenem-resistant Enterobacteriacea mediastinitis

ABSTRACT A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides or polymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%) patients. The median time to acute kidney injury was 6.0 (95% CI 3-14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6-42) days in the polymyxin with other antimicrobial combinations group (p = 0.03). Polymyxin B with aminoglycosides group progressed faster to any degree of renal dysfunction.

Pharmacodynamic profiling of commonly prescribed antimicrobial drugs against Escherichia coli isolates from urinary tract

Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: car-bapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection.

Proposta sobre uso de dados de receitas de antimicrobianos retidas: a experiência EUREQA / A proposal for using data from antimicrobial prescriptions: the EUREQA experience

A presente nota pesquisa demonstra que o uso das informações de receituário ou prescrição médica tem fundamental valor para a compreensão das correlações da dinâmica da resistência bacteriana comunitária. Além disso, a análise dos dados gerada pode ajudar a estabelecer medidas e políticas de saúde pública mais adequadas para o controle e a otimização do consumo de antimicrobianos. Para isso, o artigo usa como base o modelo lógico desenvolvido pelo Projeto EUREQA voltado para aquisição, classificação, interpretação e análise das informações relacionadas à prescrição dos antimicrobianos de uso oral.

This study demonstrates that the use of information from medical prescriptions is essential for understanding the dynamics of community bacterial resistance. The resulting analysis can also influence and help establish more adequate public health policies on the control and optimization of antimicrobial use. The article demonstrates the use of a logical model developed by the EUREQA project for acquisition, classification, interpretation, and analysis of data from prescriptions for oral antimicrobial use.

Spatial exploration of Streptococcus pneumoniae clonal clustering in São Paulo, Brazil

OBJECTIVES: To examine the spatial distribution of Streptococcus pneumoniae and its clonal patterns collected between 2002 and 2006 in São Paulo, Brazil. METHODS: As part of an observational study in São Paulo city, Brazil, S. pneumoniae isolates routinely cultured from blood, respiratory specimens, or cerebrospinal and other profound fluids were selected. Additionally, only isolates with either penicillin (PEN) intermediate (I) or resistant (R) status on routine antibiogram were included, in order to obtain a higher probability of clonal isolates. A single I/R S. pneumoniae isolate per patient was included and submitted to genotypic determination by pulsed field gel electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) were determined for the isolates by Etest® to PEN and other antimicrobials. Each isolate was geocoded in a digital map. The Kernel function and ratio methods between total isolates vs. clones were used in order to explore possible cluster formations. RESULTS: Seventy-eight (78) S. pneumoniae community isolates from two major outpatient centers in São Paulo, Brazil, were selected from the databank according to their penicillin susceptibility profile, i.e. R or I to penicillin assessed by oxacillin disc diffusion. Of these, 69 were submitted to PFGE, 65 to MIC determination, and 48 to spatial analytical procedures. Preliminary spatial analysis method showed two possible cluster formation located in southwest and southeast regions of the city. CONCLUSION: Further analyses are required for precisely determining the existence of S. pneumoniae clusters and their related risk factors. Apparently there is a specific transmission pattern of S. pneumoniae clones within certain regions and populations. GIS and spatial methods can be applied to better understand epidemiological patterns and to identify target areas for public health interventions.

A pharmacodynamic strategy to optimize empirical antibiotic therapy for gram-negative bacteria in a Brazilian Intensive Care Unit

Pharmacodynamic analyses were proposed to determine optimal empirical antibiotic therapy against Gram-negative bacteria isolated in a Brazilian ICU. Due to high resistance rates, standard regimens of cefepime, ciprofloxacin, meropenem, and piperacillin/tazobactam were not able to attain significant bactericidal CFR. Prolonged infusion of meropenem achieved 88 percent CFR, making it a possible empirical regimen in this ICU until susceptibilities become available. Still, even through administration of high dose prolonged infusions, 12.0 percent of simulated subjects did not achieve bactericidal exposure, suggesting that combination therapy would frequently be required in this setting. In conclusion, we recommend that in the presence of identified resistance problems among Gram-negative bacteria in a unit or hospital, MIC testing of formulary agents should be conducted along with pharmacodynamic simulation to assist in choosing an optimal antibiotic and dosage regimen for empirical use of severe infections until cultures and susceptibilities become available.

Antibiotic resistance and trend of urinary pathogens in general outpatients from a major urban city

OBJECTIVE: We assessed the antimicrobial resistance patterns of pathogens responsible for urinary tract infections (UTI) in outpatients in São Paulo, Brazil, as well as the Escherichia coli antimicrobial resistance trend. MATERIALS AND METHODS: Outpatients urine cultures were collected from January 2000 to December 2003. Statistical analysis considered positive results for one bacterial species with colony count > 100,000 CFU/mL. Stratification was done on age group and gender. Statistical tests used included chi-square and the chi-square test for trend to evaluate differences between susceptibility rates among age groups and ordering in the E. coli resistance rates per year, respectively. RESULTS: There were 37,261 positive results with Enterobacteriaceae isolated in 32,530 (87.3 percent) and Gram-positive cocci in 2,570 (6.9 percent) cultures. E. coli had the highest prevalence (71.6 percent). Susceptibility tests were performed in 31,716 cultures. E. coli had elevated resistance rates (> 30 percent) to ampicillin, trimethoprim-sulfamethoxazole, and tetracycline. Significant differences between age groups and ordering among years were observed. CONCLUSIONS: The use of trimethoprim-sulfamethoxazole is precluded in the population studied due to elevated resistance rates (> 30 percent) among most prevalent pathogens. Significant resistance rate differences among age groups and years were observed, particularly for fluoroquinolones. Fluoroquinolones should be used with caution. Nitrofurantoin should be used as empirical therapy for primary, non-complicated urinary tract infections.

Antimicrobial susceptibility of Gram-negative bacteria in Brazilian hospitals: the MYSTIC Program Brazil 2003

Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2003. Gram-negative bacteria (n = 1,550) causing nosocomial infections were collected at 20 Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by Etest methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). Pseudomonas aeruginosa (30.3 percent) was the most frequent isolate, followed by E. coli (18.6 percent), Klebsiella pneumoniae (16.9 percent), Acitenobacter baumannii (8.8 percent), and Enterobacter cloacae (7.1 percent). Pseudomonas aeruginosa (n=470) isolates presented susceptibility rates of 64 percent to meropenem, 63.8 percent to piperacillin/tazobactam, 63.4 percent to amikacin, 58.7 percent to imipenem. Acitenobacter baumannii presented susceptibility rates to meropenem of 97.1 percent, and 73 percent to tobramycin. E. coli and K. pneumoniae were highly susceptible to both carbapenems.Carbapenem resistance among the Enterobacteriaceae is still rare in the region. Acitenobacter baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since they play an important role in nosocomial infections in this environment, the use of empirical combination therapy to treat these pathogens may be justified.

Antimicrobial susceptibility in intensive care units: MYSTIC Program Brazil 2002

OBJECTIVE: Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2002. MATERIAL AND METHODS: Gram-negative bacteria (n = 503) causing nosocomial infections were collected at seven Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by E-test methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: Pseudomonas aeruginosa (33 percent) was the most frequently isolated, followed by A. baumannii (17.1 percent), K. pneumoniae (12.1 percent), E. coli (10.5 percent), and E. cloacae (7.9 percent). Pseudomonas aeruginosa isolates had susceptibility rates of 67.5 percent to piperacillin/tazobactam, 59.8 percent to meropenem, 57.3 percent to imipenem. A. baumannii presented susceptibility rates to meropenem of 89.5 percent, 88.4 percent to imipenem, and 74.4 percent to tobramycin. E. coli and K. pneumoniae were fully susceptible to both carbapenems. CONCLUSIONS: Carbapenem resistance among Enterobacteriaceae is still rare in this region. A. baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since these two bacterial species play an important role in nosocomial infections, the use of empirical combination therapy to treat these pathogens may be justified.

Klebsiella pneumoniae with multiple antimicrobial resistance

A Klebsiella pneumoniae strain was isolated from the urine of a patient at one of the centers participating in the 2001 edition of the MYSTIC program in Brazil. The initial phenotypic findings of the isolated K. pneumoniae presented an unusual MIC of 8 ìg/mL to meropenem, 2 ìg/mL to imipenem, elevated MICs to broad spectrum cephalosporins (ceftazidime/cefotaxime/cefepime MIC > 256 ìg/mL), aminoglycosides (gentamycin > 256 ìg/mL and tobramycin = 48 ìg/mL), piperacillin/tazobactam (MIC > 256 ìg/mL) and susceptibility to ciprofloxacin (MIC = 0.25 ìg/mL). The strain also tested positive for ESBL production with double-disk and E-test methodologies. More detailed investigation revealed that the strain produced a SHV-4 type enzyme and also lacked a 36 kDa outer membrane porin.

Estimated prevalence of immunity to poliomyelitis in the city of Säo Paulo, Brazil: a population-based survey

OBJECTIVES: Estimate the prevalence of immunity to poliomyelitis (anti-polio antibodies) in the city of Säo Paulo/Brazil through a population-based survey. METHODS: A quantitative and inductive method was used to draw a representative sample of the population. Randomization and stratification (based on sex, age and residence region) was done, and 1,059 individuals were studied on a home-visit basis (structured questionnaires and blood samples). A microneutralization test was performed to detect anti-polio antibodies against serotypes 1, 2 and 3. RESULTS: The estimated prevalence of immunity to poliomyelitis was high, with 94.6 percent prevalence of anti-polio 1 antibodies, 98.8 percent anti-polio 2 and 91.9 percent anti-polio 3. Despite this high prevalence, there were significantly lower prevalence levels in some groups, specially among age and residence region groups. DISCUSSION: Routine child immunization and NIDs with OPV have provided excellent levels of serological immunity to poliomyelitis in the population of the city of Säo Paulo, Brazil. However, there may be specific groups with a lower prevalence of immunity. Estimations of the prevalence of immunity to poliomyelitis were made in a population-based survey, which could be used as an auxiliary tool for supporting the polio eradication program

Avaliaçäo in vitro de macrolídeos e antibióticos B-lactâmicos orais ante a microrganismos isolados no tato respiratório / In vitro evaluation of oral macrolides and B-lactam antibiotics against isolated Pathogens from the respiratory tract

No período de setembro de 1999 a julho de 2000, analisamos a atividade in vitro de seis antimicrobianos, respectivamente, azitromicina, claritromicina, amoxicilina, amoxicilina/ácido clavulânico, cefprozil e cefaclor ante a um total de 597 amostras bacterianas isoladas do trato respiratório superior e inferior de pacientes da comunidade, sem restriçäo de faixa etária, assim distribuídas: 247 cepas de H. influenzae, 147 S. aureus, 114 S. pneumoniae, 51 S. pyogenes e 38 M catarrhalis. A determinaçäo da Concentraçäo Inibitória Mínima (MIC) foi realizada pelo método do Etest e interpretadas de acordo com critérios padronizados pelo NCCLS. Entre as 247 cepas de H. influenzae, 9,7 porcento eram produtoras de B-lactamase, sendo que 100 porcento destas cepas foram sensíveis à amoxicilina/ác. clavulânico e cefaclor, 98 porcento à cefprozil, 96 porcento à azitromicina e 90 porcento à claritromicina. Das 147 cepas de S. aureus, 100 porcento eram sensíveis à oxacilina, amoxilina/ác. clavulânico, cefprozil e cefaclor, 71 porcento à claritromicina e 68 porcento à azitromicina. Entre as 114 cepas de S. peneumoniae, nenhuma cepa apresentou resistência total à penicilina, 14 cepas apresentaram resistência intermediária para penicilina, sendo que 100 porcento das cepas foram sensíveis à amoxicilina e amoxicilina/àc. clavulânico, 99 porcento à cefprozil e cefaclor, 88 porcento à azitromicina e 86 porcento à claritromicina. Entre as 14 cepas de pneumococos com resistência intermediária para penicilina, 3 cepas eram resistentes à azitromicina e 4 cepas à claritromicina. Entrre as 51 amostras de S. pyogenes, 4 cepas apresentaram resistência à azitromicina e claritromicina. Para M. catarrhalis, 100 porcento das cepas eram produtoras de B-lactamase e o MIC para azitromicina, claritromicina, amoxicilina, amoxicilina/ác. clavulânico, cefprozil e cefaclor foram 0,25; 0,25; 3; 0,25; 4 e 1,5 ug/ml, respectivamente.(au)

Treatment of nosocomial pneumoniae: an experience with meropenem

This study aimed at evaluating the efficacy and safety of meropenem as first choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in Hospital das Clínicas (HC) - University of Säo Paulo; a hospital with high incidence of antimicrobial resistence. Prospective, open, and non-comparative trial with meropenem were done in patients with ventilator-assiciated or aspiration NP in 2 ICUs at HC - University od Säo Paulo. Etiologic investigation was done through bronchoalveolar lavage and blood cultures prior to study entry. Twenty-five (25) critically ill patients with NP were enrolled (mean age 40 years). Ventilator-acquired pneumonia was responsible for 76 percent of cases and aspiration NP for 24 percent. Specific etiologic agents were identified and considered to be clinically and temporally responsible for NP in 11 (44 percent) patients. A.baumanii was responsible for 6 cases (55 percent), P.aeruginosa for 3 (27 percent), and S.aureus for 2 (18 percent). At completion of treatment, 19 patients (76 percent) showed either cure (48 percent) or improvement (28 percent) after use of meropenem therapy. Mortality was 12 percent at the end therapy (8 perecent after excluding 1 non-evaluable patient). After 4 to 6 weeks of follow-up, 12 (48 percent) patients has improved or been totally cured, and overall mortality was 24 percent. Clinical complications were observed in 11 patients (44 percent), with none of them definitely related to the study drug. Meropenem as monotherapy was effective and well-tolerated in most NP patients in our ICU. The low mortality rate in this study might have been due to first choice use of this drug. Controlled, drug comparative clinical trials are needed to support this preliminary observation.