Completed genome and emergence scenario of the multidrug-resistant nosocomial pathogen Staphylococcus epidermidis ST215.

BACKGROUND: A multidrug-resistant lineage of Staphylococcus epidermidis named ST215 is a common cause of prosthetic joint infections and other deep surgical site infections in Northern Europe, but is not present elsewhere. The increasing resistance among S. epidermidis strains is a global concern. We used whole-genome sequencing to characterize ST215 from healthcare settings. RESULTS: We completed the genome of a ST215 isolate from a Swedish hospital using short and long reads, resulting in a circular 2,676,787 bp chromosome and a 2,326 bp plasmid. The new ST215 genome was placed in phylogenetic context using 1,361 finished public S. epidermidis reference genomes. We generated 10 additional short-read ST215 genomes and 11 short-read genomes of ST2, which is another common multidrug-resistant lineage at the same hospital. We studied recombination's role in the evolution of ST2 and ST215, and found multiple recombination events averaging 30-50 kb. By comparing the results of antimicrobial susceptibility testing for 31 antimicrobial drugs with the genome content encoding antimicrobial resistance in the ST215 and ST2 isolates, we found highly similar resistance traits between the isolates, with 22 resistance genes being shared between all the ST215 and ST2 genomes. The ST215 genome contained 29 genes that were historically identified as virulence genes of S. epidermidis ST2. We established that in the nucleotide sequence stretches identified as recombination events, virulence genes were overrepresented in ST215, while antibiotic resistance genes were overrepresented in ST2. CONCLUSIONS: This study features the extensive antibiotic resistance and virulence gene content in ST215 genomes. ST215 and ST2 lineages have similarly evolved, acquiring resistance and virulence through genomic recombination. The results highlight the threat of new multidrug-resistant S. epidermidis lineages emerging in healthcare settings.

Colonization with multidrug-resistant organisms is associated with impaired survival of patients with surgically resected cholangiocarcinoma.

BACKGROUND & AIMS: Colonization with multidrug-resistant organisms (MDRO) has been shown to impair survival in patients with various malignancies. Despite the increasing spread of MDRO, its impact on patients with cholangiocarcinoma (CCA) is unclear. Aim of this study was to analyse the impact of MDRO-colonization on overall prognosis in CCA patients. METHODS: All patients with surgically resected CCA diagnosed between August 2005 and November 2021 at the University Hospital Frankfurt were screened for MDRO. CCA patients with a positive MDRO screening before or within the first 90 days after diagnosis of CCA were defined as colonized. Patients with a negative MDRO screening were defined as non-colonized. RESULTS: Hundred and sixty nine patients were included. 32% (n = 54) were screened MDRO positive, while 68% (115) were non-colonized. Median overall survival (OS) for colonized patients was 17.1 months (95% CI = 9-25.2 months) compared to 50 months (95% CI = 37.1-62.8) for MDRO-negative patients (p ≤ .001). Non-cancer-related mortality (p ≤ .001) and infectious-related death (p ≤ .001) was significantly higher in the MDRO-colonized group. In multivariate analysis, MDRO colonization (HR = 2.1, 95% CI = 1.4-3.3, p = .001), ECOG 1 (HR = 2.5, 95% CI = 1.6-4, p ≤ .001) and N1 status (HR = 1.7, 95% CI = 1.1-2.6, p = .017) were independent risk factors for OS. CONCLUSION: MDRO-colonization contributes to poor survival in patients with surgically resected CCA. MDRO surveillance is necessary to optimize clinical management of infections and to potentially reduce mortality in this critical population.

Antibiogram of Multidrug-Resistant Bacteria Based on Sepsis Onset Location in Korea: A Multicenter Cohort Study.

BACKGROUND: Administration of adequate antibiotics is crucial for better outcomes in sepsis. Because no uniform tool can accurately assess the risk of multidrug-resistant (MDR) pathogens, a local antibiogram is necessary. We aimed to describe the antibiogram of MDR bacteria based on locations of sepsis onset in South Korea. METHODS: We performed a prospective observational study of adult patients diagnosed with sepsis according to Sepsis-3 from 19 institutions (13 tertiary referral and 6 university-affiliated general hospitals) in South Korea. Patients were divided into four groups based on the respective location of sepsis onset: community, nursing home, long-term-care hospital, and hospital. Along with the antibiogram, risk factors of MDR bacteria and drug-bug match of empirical antibiotics were analyzed. RESULTS: MDR bacteria were detected in 1,596 (22.7%) of 7,024 patients with gram-negative predominance. MDR gram-negative bacteria were more commonly detected in long-term-care hospital- (30.4%) and nursing home-acquired (26.3%) sepsis, whereas MDR gram-positive bacteria were more prevalent in hospital-acquired (10.9%) sepsis. Such findings were consistent regardless of the location and tier of hospitals throughout South Korea. Patients with long-term-care hospital-acquired sepsis had the highest risk of MDR pathogen, which was even higher than those with hospital-acquired sepsis (adjusted odds ratio, 1.42; 95% confidence interval, 1.15-1.75) after adjustment of risk factors. The drug-bug match was lowest in patients with long-term-care hospital-acquired sepsis (66.8%). CONCLUSION: Gram-negative MDR bacteria were more common in nursing home- and long-term-care hospital-acquired sepsis, whereas gram-positive MDR bacteria were more common in hospital-acquired settings in South Korea. Patients with long-term-care hospital-acquired sepsis had the highest the risk of MDR bacteria but lowest drug-bug match of initial antibiotics. We suggest that initial antibiotics be carefully selected according to the onset location in each patient.

[Patient- and provider-related factors in the success of multidrug tuberculosis treatment in ColombiaFatores de êxito do tratamento da tuberculose multirresistente relacionados com o paciente e com a equipe de saúde na Colômbia]. / Factores de éxito del tratamiento de la tuberculosis multidrogorresistente relacionados con el paciente y el personal sanitario en Colombia.

OBJECTIVE: To identify patient- and provider-related factors associated with the success of multidrug-resistant tuberculosis (MDR-TB) treatment in the six municipalities of Colombia with the highest number of MDR-TB cases. METHODS: Bivariate and multivariate logistic regressions were used to analyze the association between treatment success (cure or treatment completion) and characteristics of the patients and physicians, nursing professionals, and psychologists involved in their treatment. The importance of knowledge in the management of MDR-TB cases was explored through focus groups with these providers. RESULTS: Of 128 cases of TB-MDR, 63 (49.2%) experienced treatment success. Only 52.9% of the physicians and nursing professionals had satisfactory knowledge about MDR-TB. Logistic regression showed that being HIV negative, being affiliated with the contributory health insurance scheme, being cared for by a male physician, and being cared for by nursing professionals with sufficient knowledge were associated with a successful treatment outcome (p ≤ 0.05). Qualitative analysis showed the need for in-depth, systematic training of health personnel who care for patients with MDR-TB. CONCLUSIONS: Some characteristics of patients and healthcare providers influence treatment success in MDR-TB cases. Physicians' and nurses' knowledge about MDR-TB must be improved, and follow-up of MDR-TB patients who are living with HIV and of those affiliated with the subsidized health insurance scheme in Colombia must be strengthened, as these patients have a lower likelihood of a successful treatment outcome.

OBJETIVO: Identificar os fatores associados ao êxito do tratamento da tuberculose multirresistente (TBMR) relacionados ao paciente e à equipe de saúde nos seis municípios da Colômbia com o maior número de casos. MÉTODOS: Mediante regressão logística bifatorial e multifatorial, analisou-se a associação entre o êxito do tratamento (cura ou completude do tratamento) e as características dos pacientes e dos médicos, profissionais de enfermagem e psicólogos envolvidos neste. Explorou-se a importância do conhecimento no manejo de casos de TBMR mediante grupos focais com os mesmos profissionais. RESULTADOS: Dos 128 casos de TBMR, 63 (49.2%) lograram êxito no tratamento. Somente 52.9% dos médicos e profissionais de enfermagem tinham conhecimentos satisfatórios sobre TBMR. A regressão logística demonstrou que soronegatividade para o HIV, cobertura pelo sistema de saúde sob o regime de contribuinte, atendimento por um médico do sexo masculino e atendimento por profissionais de enfermagem com conhecimento suficiente foram fatores associados ao êxito do tratamento (p ≤ 0,05). A análise qualitativa demonstrou necessidade de aprofundar e sistematizar a capacitação do pessoal de saúde que atende casos de TBMR. CONCLUSÕES: Algumas características do paciente e da equipe de saúde influenciam no êxito do tratamento de casos de TBMR. É preciso fortalecer os conhecimentos dos médicos e profissionais de enfermagem sobre a TBMR e reforçar o seguimento dos pacientes com TBMR que vivem com HIV e os filiados ao sistema de saúde colombiano pelo regime subsidiado, os quais têm menor probabilidade de êxito do tratamento.

Bacterial sepsis : Diagnostics and calculated antibiotic therapy.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ß­lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).

[Bacterial sepsis : Diagnostics and calculated antibiotic therapy]. / Bakterielle Sepsis : Diagnostik und kalkulierte Antibiotikatherapie.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

BACKGROUND/AIMS: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. METHODS: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. RESULTS: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). CONCLUSION: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

[Precision medicine in infectious diseases]. / Präzisionsmedizin in der Infektiologie.

Infectious medicine faces a variety of challenges, such as the increase in antibiotic resistance and the emergence and spread of infectious diseases fueled by climate change and globalization. Precision medicine can provide solutions to many of these challenges. Since an untargeted request for diagnostic tests can lead to test results without clinical relevance, which can increase the use of non-indicated antibiotics, the principle aimed at is: targeted diagnostics (the right test) and consideration of patient characteristics (the right person) to optimize management (the right action). At the same time, one must always decide whether empirical therapy must be immediately initiated, even if the results of the initiated diagnostics are not yet available. In addition, many new diagnostics as well as therapies have recently been developed for the rapid detection and more specific treatment of bacterial infections. Molecular genetic methods, which offer more rapid results than classical bacterial cultures, are gaining ground as new diagnostics. New therapeutics such as bacteriophages, antibodies or antibacterial peptides allow increasingly precise treatment of certain bacterial infections. Precision medicine will also play an increasingly important role in infectious medicine in the future.

Risk factors for hospital mortality in intensive care unit survivors: a retrospective cohort study.

BACKGROUND: Deaths can occur after a patient has survived treatment for a serious illness in an intensive care unit (ICU). Mortality rates after leaving the ICU can be considered indicators of health care quality. This study aims to describe risk factors and mortality of surviving patients discharged from an ICU in a university hospital. METHODS: Retrospective cohort study carried out from January 2017 to December 2018. Data on age, sex, length of hospital stay, diagnosis on admission to the ICU, hospital discharge outcome, presence of infection, and Simplified Acute Physiology Score (SAPS) III prognostic score were collected. Infected patients were considered as those being treated for an infection on discharge from the ICU. Patients were divided into survivors and non-survivors on leaving the hospital. The association between the studied variables was performed using the logistic regression model. RESULTS: A total of 1,025 patients who survived hospitalization in the ICU were analyzed, of which 212 (20.7%) died after leaving the ICU. When separating the groups of survivors and non-survivors according to hospital outcome, the median age was higher among non-survivors. Longer hospital stays and higher SAPS III values were observed among non-survivors. In the logistic regression, the variables age, length of hospital stay, SAPS III, presence of infection, and readmission to the ICU were associated with hospital mortality. CONCLUSIONS: Infection on ICU discharge, ICU readmission, age, length of hospital stay, and SAPS III increased risk of death in ICU survivors.

Decreasing Antibiotic Resistance Trends Nationally in Gram-Negative Bacteria Across United States Veterans Affairs Medical Centers, 2011-2020.

INTRODUCTION: Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria. METHODS: The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic. RESULTS: Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p < 0.05). The largest decreases were seen in carbapenem-resistant phenotypes of P. mirabilis, Klebsiella, and M. morganii (AAPCs: - 22.9%, - 20.7%, and - 20.6%, respectively). In 2020, percent susceptibility was over 80% for all organisms tested against aminoglycosides, cefepime, ertapenem, meropenem, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. CONCLUSION: We observed significant decreases in antibiotic resistance for P. aeruginosa and Enterobacterales over the past decade. According to the 2020 antibiogram, in vitro antimicrobial activity was observed for most treatment options. These results may be related to the robust infection control and antimicrobial stewardship programs instituted nationally among VAMCs.

Reducing the duration of antibiotic therapy in surgical patients through a specific nationwide antimicrobial stewardship program. A prospective, interventional cohort study.

BACKGROUND: Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to reduce the duration of treatments in surgical patients to <7 days. METHODS: Prospective cohort study evaluating surgical patients receiving antibiotics ≥7 days in 32 hospitals. Indication for treatment, quality of source control, type of recommendations issued, and adherence to the recommendations were analysed. Temporal trends in the percentages of patients with treatment >7 days were evaluated using a linear regression model and Pearson's correlation coefficients. RESULTS: A total of 32 499 patients were included. Of these, 13.7% had treatments ≥7 days. In all, 3912 stewardship interventions were performed, primarily in general surgery (90.7%) and urology (8.1%). The main types of infection were intra-abdominal (73.4%), skin/soft tissues (9.8%) and urinary (9.2%). The septic focus was considered controlled in 59.9% of cases. Out of 5458 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (21.7%), metronidazole (11.2%), amoxicillin/clavulanate (10.3%), meropenem (10.7%), ceftriaxone (9.3%) and ciprofloxacin (6.7%). The main recommendations issued were: treatment discontinuation (35.0%), maintenance (40.0%) or de-escalation (15.5%), and the overall adherence rate was 91.5%. With adequate source control, the most frequent recommendation was to terminate treatment (51.2%). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (Pc=-0.69;P < 0.001). CONCLUSIONS: This stewardship programme reduced the duration of treatments in surgical departments. Preference was given to general surgery services, intra-abdominal infection, and beta-lactam antibiotics, including carbapenems. Adherence to the issued recommendations was high.

[Treatment refractory multidrug-resistant bacterial keratitis]. / Therapierefraktäre 4-MRGN-Keratitis.

This article reports a case of severe, treatment refractory infectious keratitis. Multiple samples of the cornea and the anterior chamber were taken without detection of any pathogens. Ultimately a multidrug-resistant Pseudomonas aeruginosa was isolated and successfully treated with tobramycin and amikacin, according to its antibiotic sensitivity. If there is a clinical suspicion multiple samples should be taken and multidrug-resistant pathogens considered as a differential diagnosis.

Hand Hygiene Practices, Attitudes, and Microbial Hand Populations of Practicing Doctors of Chiropractic.

OBJECTIVE: Hand hygiene practice is important in health care settings to reduce the spread of infection. To date, no hand hygiene study has been conducted with doctors of chiropractic that included microbiological analysis of hand specimens. The primary objective of this study was to examine the relationship between self-reported hand hygiene practices and attitudes of chiropractors with the number and type of pathogenic bacteria and yeast present on their hands. METHODS: In this cross-sectional study, a microbiological analysis of the chiropractor's dominant hand was performed along with completion of a survey concerning practices and attitudes regarding hand hygiene. The relationship between self-reported measures with laboratory findings was conducted using generalized linear modeling. RESULTS: Participants who responded to the survey indicated that hand hygiene was important, and most reported performing hand hygiene before and/or after patient contact. However, 7 (26.9%) participants had multidrug-resistant bacteria isolated from their hands. There was no correlation between the survey responses and hand specimens with the exception of the number of handwashing episodes. From the hand specimens, 16 (45.7%) coagulase-negative staphylococci isolates were oxacillin resistant, and 9 (25.7%) were multidrug resistant. CONCLUSION: This study found that like other health care workers, chiropractors had antimicrobial-resistant bacteria on their hands, some of which were multidrug resistant. Multidrug resistant bacteria have the potential to be transferred to patients and patient contact surfaces. These findings indicate that chiropractic offices could play a role in health care-associated infections. Formal hand hygiene training should be included as part of the chiropractic education curriculum and continuing education for doctors of chiropractic.

[The Age of Multidrug Resistance: Ten Year Incidence in a Neonatal Intensive Care Unit]. / A Era da Multirresistência: Incidência em Dez Anos Numa Unidade de Cuidados Intensivos Neonatais.

INTRODUCTION: The emergence of multidrug-resistant bacteria is a medical challenge nowadays. The objective of the present study was to determine the incidence of multidrug-resistant bacteria infections in a neonatal Intensive Care unit. MATERIAL AND METHODS: Retrospective, descriptive, incidence study of infectious episodes by multidrug-resistant bacteria from 2008 to 2017 in a differentiated perinatal support unit. RESULTS: Sixty-four infectious episodes included (median gestational age of 28 weeks and birth weight of 885 g). The isolated bacteria were: Enterobacteriaceae (n = 46); Methicillin-resistant Staphylococcus aureus (n = 12); Acinetobacter baumannii (n = 4); Pseudomonas aeruginosa (n = 2). A risk factor was identified in 90.6% of the episodes, with emphasis on central catheter (89%) and previous antibiotic therapy (78%). The lethality rate of these infections was 10.9% (Unit mortality rate: 4.4%). The overall incidence rate was 3.2 infectious episodes/100 hospitalizations, corresponding to 1.7 episodes/1000 days of hospitalization. There were three infectious outbreaks, with an increasing impact of Enterobacteriaceae. DISCUSSION: The reported incidence rate reflects a risk population, hospitalized in an Intensive Care unit, over a long period of time. The distribution of isolated bacteria, with Enterobacteriaceae predominance, is in accordance with the shift in multidrug resistance reported worldwide. The outbreaks point to the need of understanding risk factors and means of local dissemination. The relevance of these infections is evident in their lethality rate, which is higher compared to that of general hospital infections. CONCLUSION: The incidence rate reflects the local dimension of the problem, representing a quality indicator which is relevant for controlling these infections.

Introdução: A emergência de bactérias multirresistentes constitui um desafio médico na atualidade. O objetivo do presente estudo foi determinar a incidência das infeções por bactérias multirresistentes numa unidade de Cuidados Intensivos Neonatais. Material e Métodos: Estudo de incidência, retrospetivo, descritivo dos episódios infeciosos por bactérias multirresistentes, de 2008 a 2017, numa unidade de apoio perinatal diferenciado. Resultados: Incluíram-se 64 episódios infeciosos (medianas - idade gestacional: 28 semanas; peso ao nascimento: 885 g). As bactérias isoladas foram: Enterobacteriaceae (n = 46); Staphylococcus aureus meticilino-resistente (n = 12); Acinetobacter baumannii (n = 4); Pseudomonas aeruginosa (n = 2). Identificou-se um fator de risco em 90,6% dos episódios, destacando-se cateter central (89%) e antibioticoterapia prévia (78%). A taxa de letalidade associada foi 10,9% (taxa de mortalidade unidade: 4,4%). A incidência global foi 3,2 episódios infeciosos/100 internamentos, correspondentes a 1,7 episódios/1000 dias de internamento. Verificaram-se três surtos infeciosos com impacto crescente de Enterobacteriaceae.Discussão: A taxa de incidência descrita reflete uma população de risco, internada numa unidade de Cuidados Intensivos e num período longo de tempo. A distribuição das bactérias isoladas evidencia a evolução da multirresistência relatada internacionalmente, com predomínio crescente de Enterobacteriaceae. A ocorrência de surtos aponta para a necessidade de perceber fatores de risco e meios de disseminação local. A relevância destas infeções está patente na taxa letalidade, superior às infeções hospitalares em geral. Conclusão: A taxa de incidência reflete a dimensão local do problema, constituindo um indicador de qualidade, relevante para o controlo destas infeções.

Broad spectrum antibiotics in newborns increase multi-drug resistant infections.

Our objective was to determine if broad spectrum antibiotics (BSA) are associated with multi-resistant bacterial (MRB) infections in neonatal patients. We conducted a case-control study with two groups of patients: those with and without a MRB infection. We included 43 cases and 43 controls. MRB strains were: 21 S. maltophila (49%), 11 ESBL-producing Enterobacteriae (25%), 8 P. aeruginosa (19%) and 3 MRSA (7%). Odds ratio (OR) for MRB after seven days of carbapenems was 4.25 (95% confidence interval (CI) 1.4-17.4) and OR for MRB after seven days of third generation cephalosporin was 8 (95% CI 1.1-34.9). BSA longer than seven days, increases MRB infections 22.5 times in patients with bronchopulmonary dysplasia (BPD). Our data show a clear association between the use of BSA and the development of MRB infections, especially in BPD. Although we cannot state this is a causal relationship, we can recommend avoiding prolonged treatment with these antibiotics in preterm babies at risk of BPD.

[Antimicrobial Susceptibility Patterns in Outpatient Urinary Tract Infection in the District of Coimbra, Portugal: A Cross-Sectional Study]. / Perfil de Sensibilidade aos Antibióticos na Infeção Urinária em Ambulatório no Distrito de Coimbra: Um Estudo Transversal.

INTRODUCTION: Urinary tract infections in the community setting are quite common. It is necessary to be aware of antibiotic susceptibility patterns in order to provide rational empirical therapy. The aim of this study is to determine the frequency and antimicrobial susceptibility of the strains responsible for urinary tract infections in primary health care, in the district of Coimbra, Portugal. MATERIAL AND METHODS: In this observational and cross-sectional study, we analyzed 7134 positive urine cultures of outpatient laboratories in the district of Coimbra, over one year. In most cases, a positive culture was defined by a threshold of 105 colony-forming units per milliliter and was conducted by the automated system VITEK® 2, by bioMérieux. We used descriptive and inferential statistics to determine the prevalence and antimicrobial susceptibility of bacteria and to ascertain whether there were differences associated with sex and age. RESULTS: From the total of positive cultures, 83.4% pertained to females and 41.0% to individuals over 75 years old. Escherichia coli was the most frequent strain (63.9%), although its prevalence was lower (p < 0.001) in males and individuals over 75 years old. Its susceptibility to fosfomycin and nitrofurantoin was higher than 95% and with ciprofloxacin and trimethoprim/sulfamethoxazole it was lower than 80%. Resistances were more frequent (p < 0.001) in males and in the elderly. DISCUSSION: Escherichia coli was the most frequent strain, revealing less resistance to fosfomycin and nitrofurantoin. Antimicrobial susceptibility was lower in the elderly and in males, populations in whom empirical therapy may be less successful. CONCLUSION: In order to improve clinical results, we recommend periodic surveillance of antimicrobial susceptibility, which could enable the provision of efficient information to clinicians, namely those who prescribe empirically for such infections, as well as standardization of identification methods of bacterial strains diagnosis and of the antibiotic kits to be tested.

Introdução: As infeções do trato urinário são muito frequentes na comunidade. É essencial conhecer o padrão de sensibilidade aos antibióticos para uma terapêutica empírica racional. O objetivo deste estudo é determinar a prevalência e o perfil de suscetibilidade aos antibióticos dos microrganismos implicados em infeções urinárias a nível dos cuidados primários de saúde, no distrito de Coimbra.Material e Métodos: Neste estudo observacional e transversal, analisámos 7134 uroculturas positivas de laboratórios de ambulatório do distrito de Coimbra, no período de um ano. Na maioria dos casos, a urocultura positiva foi definida por um limiar de 105 unidadesformadoras de colónias por mililitro e executada através do sistema automatizado VITEK® 2, da bioMérieux. Usámos estatística descritiva e inferencial para determinar a prevalência e a sensibilidade aos antibióticos dos microrganismos e averiguar a relação destas com o sexo e com a idade.Resultados: Do total de uroculturas positivas, 83,4% pertencia ao sexo feminino e 41,0% pertencia à população acima dos 75 anos. A Escherichia coli foi o microrganismo mais frequente (63,9%), mas a sua prevalência foi inferior (p < 0,001) no sexo masculino e acima dos 75 anos. A sua sensibilidade à fosfomicina e à nitrofurantoína foi superior a 95% e à ciprofloxacina e ao cotrimoxazol foi inferior a 80%. As resistências foram mais frequentes (p < 0,001) no sexo masculino e nos mais idosos.Discussão: A Escherichia coli foi o microrganismo mais frequente, verificando-se menores percentagens de resistência desta à fosfomicina e à nitrofurantoína. A sensibilidade aos antibióticos foi menor em idades mais avançadas e também no sexo masculino (p < 0,001), populações onde a antibioterapia empírica pode ter maior risco de insucesso.Conclusão: Recomendamos a monitorização periódica do perfil de sensibilidade aos antibióticos, para eficaz informação aos médicos que têm de proceder a terapêutica empírica deste tipo de infeções, bem como a uniformização das técnicas de identificação das estirpes bacterianas e dos conjuntos de antibióticos a serem testados nos antibiogramas.

Hospital-Acquired Pneumonia in a Multipurpose Intensive Care Unit: One-Year Prospective Study.

INTRODUCTION: Hospital-acquired pneumonia continues to be a frequent complication in the intensive care unit and an important cause of admission in the intensive care unit. The aim of our study was to evaluate the demography, incidence, risk factors, causative bacterial pathogens and outcome of all episodes of Hospital-acquired pneumonia in our unit. MATERIAL AND METHODS: Prospective observational study, at a tertiary university hospital during one year (2014) including all the cases of hospital-acquired pneumonia in the intensive care unit. RESULTS: Sixty patients were identified with pneumonia. Thirty-five (58.3%) had an intensive care unit acquired pneumonia, corresponding to 6.9 cases/1000 intubation-days. Antibiotic treatment in the previous 30 days was present in 75% of the cases. The incidence of Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii was 26.2%, 20.0% and 9.2%, respectively. Patients with late-onset hospital-acquired pneumonia (≥ 7 days) showed higher frequency of non-fermenting Gram-negative bacilli isolates, and methicillin-resistant S. aureus. Combination therapy was performed in 67.0%, and de-escalation in 18.3%. The mortality rate was 18.3%. The adjusted odds ratio for intensive care unit mortality in the group of patients with non-intensive care unit acquired pneumonia was 5.2 (95% CI of 1.02 - 22.10; p = 0.046). DISCUSSION: The knowledge of local bacterial flora and resistance patterns is of crucial importance and strongly recommended. This evidence increases the probability of success of empiric antibiotic therapy. CONCLUSION: S. aureus was the predominant causative agent of nosocomial pneumonia. The most frequent risk factor identified for infection with multidrug-resistant organisms was previous treatment with antibiotics. Multidrug-resistant organisms were present in 45% of documented hospital-acquired pneumonias. In admitted patients with non-intensive care unit acquired pneumonia, the intensive care unit mortality rate was nearly five times higher compared to intensive care unit acquired pneumonia.

Introdução: A pneumonia adquirida no hospital é uma complicação frequente nos doentes críticos e uma importante causa de admissão nos Cuidados Intensivos. O objetivo deste estudo foi avaliar a demografia, incidência, fatores de risco, microbiologia e outcome da pneumonia nosocomial num Serviço de Medicina Intensiva. Material e Métodos: Estudo prospectivo e observacional, num hospital universitário terciário, durante o período de um ano (2014). Resultados: Foram avaliados 60 doentes. Trinta e cinco (58,3%) com pneumonia nosocomial adquirida no Serviço de Medicina Intensiva, correspondendo a 6,9 casos/1000 dias de intubação. A antibioterapia nos últimos 30 dias esteve presente em 75% dos casos. A incidência de Staphylococcus aureus, Pseudomonas aeruginosa e Acinetobacter baumannii foi de 26,2%, 20,0% e 9,2% respetivamente. Os doentes com pneumonia de início tardio (≥ 7 dias) apresentaram maior frequência de bacilos Gram-negativos não-fermentadores e S. aureus resistente à meticilina. A antibioterapia em associação foi aplicada em 67,0% e a descalação em 18,3% dos doentes. A taxa de mortalidade foi 18,3%. O odds ratio ajustado de mortalidade no grupo de doentes críticos com pneumonia nosocomial adquirida fora da UCI foi de 5,2 (95% CI de 1,02 ­ 22,10; p = 0,046). Discussão: O conhecimento da flora local bacteriana e os padrões de resistência bacteriana são de grande importância e amplamente recomendados. Esta evidência aumenta a probabilidade de sucesso da antibioterapia empírica. Conclusão: O S. aureus foi o agente causador predominante da pneumonia. O fator de risco mais frequente para infecção por organismos multirresistentes foi o tratamento prévio com antibióticos. Organismos multirresistentes estavam presentes em 45% das pneumonias adquiridas no hospital de origem bacteriana comprovada. O grupo de doentes críticos com pneumonia nosocomial não adquirida no Serviço de Medicina Intensiva apresentou um risco de mortalidade cerca de cinco vezes maior comparativamente aos doentes com pneumonia nosocomial adquirida no Serviço de Medicina Intensiva.

Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes.

Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this review, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.

Resistencia antimicrobiana, una pandemia silenciosa / Antimicrobial resistance, a silent pandemic / Resistência antimicrobiana, uma pandemia silenciosa

Introducción: la resistencia a los antimicrobianos ha sido una problemática creciente a nivel global, la problemática afecta no solo la salud de personas, animales y el ambiente en general, sino que ha generado impactos de índole productivo y comercial. Una de las estrategias para abordar esta problemática es el enfoque de una salud. Este enfoque destaca la participación multidisciplinaria para combatir la resistencia antimicrobiana; y es así que cada profesión o actividad laboral genera unas responsabilidades innatas para la profesión veterinaria. Los veterinarios tienen un rol fundamental para este propósito, ya que son ellos quienes integran la aplicabilidad de estrategias de promoción y prevención a nivel agropecuario, y de consolidación e interlocución entre los diferentes componentes del enfoque (animal, humano, ambiente) desde el ámbito de la salud pública veterinaria. Materiales y Método: se realizó una búsqueda de la literatura en diferentes bases de datos, con el objetivo de realizar una revisión actualizada sobre la resistencia antimicrobiana. Resultados: dentro de las principales estrategias se debería fomentar un uso adecuado y bajo prescripción de antimicrobianos en la producción animal. Promover buenas prácticas de higiene, bioseguridad y vacunación, facilitando un correcto diagnóstico de enfermedades infecciosas en animales. Discusión: la adopción de normas internacionales para el uso responsable de los antibióticos y las directrices establecidas por la Organización Mundial de la Salud y Organización de las Naciones Unidas para la Alimentación y la Agricultura, a través del Codex Alimentarius y la Organización Mundial de Sanidad Animal, son fundamentales para hacer frente al desafío que representa el problema de la resistencia a los antimicrobianos.

Introduction: Antimicrobial resistance has been a growing problem at a global level, affecting not only the health of people, animals and the environment in general, but it has also generated impacts of a productive and commercial nature. One of the strategies to address this problem is the one-health approach. This approach emphasizes multidisciplinary participation to combat antimicrobial resistance; and thus, each profession or work activity generates innate responsibilities for the veterinary profession. Veterinarians have a fundamental role for this purpose, since they are the ones who integrate the applicability of promotion and prevention strategies at the agricultural level, and of consolidation and interlocution between the different components of the approach (animal, human, environment) from the field of veterinary public health. Materials and Method: a literature search was carried out in different databases, with the aim of carrying out an updated review on antimicrobial resistance. Results: one of the main strategies should be to promote an adequate use and under prescription of antimicrobials in animal production. Promote good hygiene, biosecurity and vaccination practices, facilitating a correct diagnosis of infectious diseases in animals. Discussion: the adoption of international standards for the responsible use of antibiotics and the guidelines established by the World Health Organization and the Food and Agriculture Organization of the United Nations, through Codex Alimentarius and the World Organization for Animal Health, are fundamental to face the challenge posed by the problem of antimicrobial resistance.

Introdução: A resistência antimicrobiana tem sido um problema crescente em todo o mundo, afetando não apenas a saúde dos seres humanos, dos animais e do meio ambiente em geral, mas também causando impactos na produção e no comércio. Uma das estratégias para lidar com esse problema é a abordagem One Health. Essa abordagem enfatiza o envolvimento multidisciplinar no combate à resistência antimicrobiana, com cada profissão ou atividade de trabalho gerando responsabilidades inatas à profissão veterinária. Os veterinários têm um papel fundamental nesse sentido, pois são eles que integram a aplicabilidade das estratégias de promoção e prevenção em nível agropecuário e de consolidação e interlocução entre os diferentes componentes da abordagem (animal, humano, ambiental) do campo da saúde pública veterinária. Materiais e Métodos: foi realizada uma pesquisa bibliográfica em diferentes bases de dados, com o objetivo de realizar uma revisão atualizada sobre a resistência antimicrobiana. Resultados: uma das principais estratégias deve ser a promoção do uso adequado e com baixa prescrição de antimicrobianos na produção animal. Promover boas práticas de higiene, biossegurança e vacinação, facilitando o diagnóstico correto de doenças infecciosas em animais. Discussão: A adoção de padrões internacionais para o uso responsável de antibióticos e as diretrizes estabelecidas pela Organização Mundial da Saúde e pela Organização das Nações Unidas para Agricultura e Alimentação, por meio do Codex Alimentarius e da Organização Mundial de Saúde Animal, são essenciais para enfrentar o desafio representado pelo problema da resistência antimicrobiana.

Factors associated with multidrug-resistant bacteria in healthcare-associated infections: a pediatric intensive care unit case-control study

ABSTRACT Objective To investigate the prevalence of factors related to healthcare-associated infections, caused by multidrug-resistant bacteria, in a pediatric intensive care unit. Methods A retrospective case-control study conducted from January 1, 2007 to December 31, 2018, in São Paulo (SP), Brazil. The study was carried out at the pediatric intensive care unit of a high-complexity, tertiary care general hospital. The study included patients aged 1 month to 19 years, admitted to the pediatric intensive care unit, diagnosed as healthcare-associated infections. Results There was significant evidence of infection by multidrug-resistant bacteria associated with immunosuppressed patients (p<0.001), in whom the likelihood of multidrug-resistant bacteria infection was estimated to be nine-fold higher than among non-immunosuppressed patients (OR 8.97; 95%CI 2.69-29.94). In the analysis of multiple logistic regression model, we observed that immunosuppressed patients had an 8.5-fold higher chance of multidrug-resistant bacteria infection when compared to non-immunosuppressed patients (OR 8.48; 95%CI 2.54-28.35; p=0.001). There is evidence of association between the Case Group and presence of Gram-positive (p=0.007), coagulase-negative Staphylococcus (p<0.001), and Gram-negative (p=0.041) microorganisms. Conclusion The immunocompromised-state variable is a factor related to healthcare-associated infections caused by multidrug-resistant bacteria, and the Case Group presented higher proportions of Gram-positive microorganisms and coagulase-negative Staphylococcus.