Clinical Outcomes and Treatment Strategies in Patients With Non-Carbapenemase-producing Carbapenem-Resistant Versus Carbapenem-Susceptible Enterobacterales Infections.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are difficult to treat and can cause significant morbidity and mortality, however most data reflect carbapenemase-producing infections. OBJECTIVE: Our objective was to evaluate clinical outcomes of non-carbapenemase-producing CRE (nCP-CRE) compared with carbapenem-susceptible Enterobacterales (CSE) infections. METHODS: This was a retrospective, multicenter, observational study (January 1, 2018 to December 31, 2020). The primary outcome was clinical success at 30 days with secondary outcomes, including clinical success at 90 days, clinical success based on treatment for nCP-CRE, persistent bacteremia, intensive care unit (ICU) admission, length of stay, and rate of Clostridioides difficile or multidrug resistant infections. RESULTS: The final analysis included 211 patients: 142 (67%) with CSE and 69 (33%) with nCP-CRE infections. Prior carbapenem exposure was more common with nCP-CRE (15% vs 4%, P = 0.01). Clinical success at 30 days was similar between groups (77% vs 74%, P = 0.73). There were no differences in secondary outcomes. There was an overall low use of carbapenems (empiric 6%, definitive 7%). Most nCP-CRE infections were treated with a monotherapy carbapenem-sparing regimen (empiric 88%, definitive 90%). Limitations include the retrospective design and the high rate of urinary infections. CONCLUSION AND RELEVANCE: Our study found no difference in clinical outcomes between nCP-CRE and CSE infections. Application of this study with future studies would help in determining optimal regimens for these infections.

The incidence of intestinal colonization of carbapenem-resistant Enterobacterales and its risk factors for bloodstream infection / 中华检验医学杂志

Objective:The aim of this study was to determine the colonization rate of carbapenem-resistant Enterobacterales (CRE) and identify the proportion and risk factors for bloodstream infection.Methods:This was a retrospective study conducted at the Department of Clinical Laboratory, Peking University People′s Hospital from January 2018 to December 2021. A total of 4 993 patients underwent rectal swab CRE screening for CRE, of which 137 were found to be positive. Clinical and laboratory data of the positive patients were collected, and the following parameters were analyzed: the positive rate of CRE screening in high-risk population, the species of colonized bacteria, antimicrobial resistance and the risk factors of CRE bloodstream infection in colonized patients. Statistical analysis was performed using SPSS 26.0 software. Univariate analysis was conducted using the chi-square (χ 2) test, while multivariate analysis was performed using binary logistic regression. The results were expressed as relative risk (odds ratio, OR) and 95% confidence interval ( CI). A significance level of 0.05 was considered statistically significant. The drug resistance rate of pathogen was analyzed by WHONET 5.6 software. Results:During the study period, a total of 4 991 patients who underwent rectal swab screening were eligible for inclusion, of which 137 patients were screened positive, resulting in a positive rate of 2.7% (137/4 991). The positive rates were higher in the intensive care ward and hematology ward, with rates of 5.5% (27/493) and 3.3% (109/3 321), respectively. A total of 145 colonization strains were isolated from patients with positive CRE screening, including 63 strains of Klebsiella pneumoniae (43.4%, 63/145), 52 strains of Escherichia coli (35.9%, 52/145), 16 strains of Enterobacter cloacae (11.0%, 16/145) and 14 strains of other Enterobacterales (9.7%, 14/145). The metal β-lactamase production type was the main component of CRE positive colonizing bacteria. The antimicrobial resistance of 145 strains to 22 antibacterial agents revealed that amikacin and tigacycline were the most sensitive. Among 137 CRE screening-positive patients, 14 (10.2%, 14/137) developed bloodstream infection. The isolated pathogenic bacteria included 10 Klebsiella pneumoniae strains and 4 Escherichia coli strains, with a predominant serine carbapenemase producing. Notably, the enzyme type and antimicrobial resistance of the bloodstream infection isolates in the same patient were highly consistent with those of the previous screening strains. Comparison was made between patients with positive CRE screening and those with CRE conversion to bloodstream infection. The unifactor analysis revealed significant differences in surgical history, neutropenia, hematopoietic stem cell transplantation, history of antibiotic use before rectal swab screening, screening within 48 hours after admission, and serine carbapenemase production by strains ( P<0.05). The multivariate analysis indicated that surgical history ( OR 24.659, 95% CI 2.540-239.411, P=0.006) and neutropenia ( OR 93.796, 95% CI 6.294-1 397.804, P=0.001) remained significantly associated with the risk of CRE bloodstream infection ( P<0.05). Conclusions:The CRE colonization rate was low in our hospital, but the proportion of patients with positive screening converted to bloodstream infection was high. Surgical history and neutropenia are risk factors for bloodstream infection transmission. Thus, it is essential to enhance monitoring in high-risk areas and susceptible patients.

ß-lactamasas de espectro extendido y factores de virulencia en Escherichia coli uropatógenas en asilos de ancianos en Lima, Perú / ß-lactamases and virulence factors in uropathogenic Escherichia coli in nursing homes in Lima, Peru

RESUMEN Los asilos de ancianos son instituciones con una alta prevalencia de infecciones del tracto urinario ocasionado por Escherichia coli productoras de ß-lactamasas de espectro extendido (BLEE), con diversos factores de virulencia. El objetivo del estudio fue determinar la frecuencia del gen bla CTX-M y de ocho genes de virulencia en 35 E. coli uropatógenas productoras de BLEE provenientes de seis asilos en Perú, durante el 2018. El 57,1% (20/35) de las E. coli fueron portadores del gen bla CTX-M. Además, se obtuvo una frecuencia del 46% (15/35) y 37% (13/35) de hly-alfa y cnf-1, respectivamente; elevada presencia de los genes iucC (63%, 22/35), aer (94%, 33/35) y chuA (94%, 33/34) y una frecuencia del 46% (16/35) y del 91% (32/34) de los genes pap GII y nanA, respectivamente. Existe predominancia en la distribución del gen bla CTX-M, además de una alta frecuencia de exotoxinas que le confieren una ventaja competitiva para diseminarse hacia el torrente sanguíneo.

ABSTRACT Nursing homes are institutions with high prevalence of urinary tract infections caused by ESBL-producing E. coli with several virulence factors. The aim of this study was to determine the frequency of the bla CTX-M gene and eight virulence genes in 35 ESBL-producing uropathogenic E. coli from six nursing homes in Peru during 2018. Of the E. coli samples, 57.1% (20/35) were carriers of the bla CTX-M gene. Furthermore, we obtained frequencies of 46% (15/35) and 37% (13/35) for hly-alpha and cnf-1, respectively; we also found high presence of the iucC (63%, 22/35), aer (94%, 33/35) and chuA genes (94%, 33/34) as well as a frequency of 46% (16/35) and 91% (32/34) for the pap GII and nanA genes, respectively. The bla CTX-M gene is predominant and a high frequency of exotoxins gives it a competitive advantage for spreading into the bloodstream.

Ceftazidime-avibactam: effectiveness and safety in the clinical practice. A third hospital level experience / Ceftazidima-avibactam: efectividad y seguridad en práctica clínica habitual. Experiencia de un hospital de tercer nivel

Objectives: Ceftazidime/avibactam (CZA) is a third generation cephalosporin and the first non-beta-lactam beta-lactamase inhibitor combination. The main outcome was to assess the effectiveness and safety of CZA in the clinical practice.Methods: It was a retrospective observational study. The inclusion criteria were age >18 years and receipt of >24 hours of CZA between January 2016 and October 2018. Variables studied included demographic, clinical, and treatment.Results: 63 inpatients in treatment with CZA were included, 39 (61.9 %) were male and the mean (SD) age was 64.3 (15.8) years. Thirty-eight (60.3%) patients presented bacteremia and 28 (44.4%) were admitted in Intensive Care Unit (ICU). Klebsiella pneumoniae were isolated in 43 (68.3) patients, and OXA-48 carbapenemase in 51 (81.0%). Concomitant antibiotic was used in 40 (63.5%) patients. Mortality at 14 and 30 days were 6 (9.5%) and 4 (6.3%) patients, respectively.Thirty-five (55.6%) patients reached microbiological cure and 47 (74.6%) clinical cure. Infection recurrence evaluated at 90 days was achieved in 23 (36.5%) patients. ICU admission and bacteremia showed decreased in clinical cure (p=0.023 and p=0.01, respectively). Only ICU admission had a diminution in microbiological cure (p=0.035) and bacteremia a higher recurrence evaluated at 90 days (p=0.003). Only 3 (4.8%) patients interrupted treatment because of the adverse events.Conclusions: ICU admission had demonstrated a microbiological and clinical cure decreasing. Recurrence evaluated a 90 days was statically significant higher in patients with bacteremia. CZA was a security antibiotic, with a very low incidence of treatment interruptions. (AU)

Objetivo: Ceftazidima/avibactam (CZA) es una cefalosporina de tercera generación y el primer inhibidor de beta-lactamasas no beta-lactámico. El objetivo principal fue evaluar su efectividad y seguridad en la práctica clínica.Métodos: Se realizó un estudio observacional retrospectivo. Los criterios de inclusión fueron: edad >18 años y administración de >24 horas de CZA entre enero de 2016 y octubre de 2018. Las variables estudiadas incluyeron demograficas, clínicas y de tratamiento.Resultados: Se incluyeron 63 pacientes con CZA, 39 (61,9 %) fueron hombres, media (SD) de edad de 64,3 (15,8) años. 38 (60,3%) pacientes presentaron bacteriemia y 28 (44,4%) fueron ingresados en la Unidad de Cuidados Intensivos (UCI). Klebsiella pneumoniae se aisló en 43 (68,3) pacientes y OXA-48 carbapenemasa en 51 (81,0%). 40 (63,5%) pacientes recibieron antibiótico concomitante. La mortalidad a los 14 y 30 días fue de 6 (9,5%) y 4 (6,3%), respectivamente.Treinta y cinco (55,6%) alcanzaron curación microbiológica y 47 (74,6%) curación clínica. Recurrencia de la infección a los 90 días sucedió en 23 (36,5%). El ingreso en UCI y la bacteriemia demostraron una disminución de la curación clínica (p-0,023 y p-0,01, respectivamente). El ingreso en UCI tuvo una disminución en curación microbiológica (p-0,035) y la bacteriemia en una mayor recurrencia a los 90 días (p-0,003). 3 (4,8%) interrumpieron el tratamiento por toxicidad.Conclusiones: El ingreso en UCI se relacionó con disminución de curación microbiológica y clínica. La recurrencia a los 90 días fue mayor en pacientes con bacteriemia. CZA presenta una incidencia baja de interrupciones del tratamiento. (AU)

Third-generation cephalosporin resistant Enterobacteriaceae in neonates and young infants: impact and outcome.

OBJECTIVE: Third-generation cephalosporins resistant Enterobacteriaceae (3GCR-EB) are a major threat in severely ill neonates hospitalized in Neonatal Intensive Care Units. Still, the particular impact of 3GCR-EB on outcomes in the wide neonatal population is not well-appreciated. We aimed to study the impact of 3GCR-EB on the length of hospital stay and mortality of a general population of neonates and young infants. STUDY DESIGN: This was a retrospective cohort study of neonates and young infants born in eight Israeli hospitals between 2009 and 2013, with a culture taken within three months after birth that tested positive for Enterobacteriaceae (EB). Data for this study were taken from centralized electronic health records included inpatient, outpatient, socio-demographic, administrative and laboratory information. The main outcomes were length of stay and mortality. The main explanatory variable was an isolation of 3GCR-EB in any bacterial culture taken from a neonate or young infant. RESULTS: Cultures were taken for 31,921 neonates and young infants; 2647 (8.3%) tested positive for EB and 290 (11%) tested positive for 3GCR-EB. Length of stay for those who tested positive was 2.8 times longer (95%CI: 2.70-2.91, p ˂ .001) than patients who tested positive for 3GC-susceptible EB. 3GCR-EB were also associated with increased mortality (OR: 12.06, 95%CI: 4.92-32.29). CONCLUSIONS: Neonates with third-generation cephalosporins resistant Enterobacteriaceae had extended hospitalization and increased mortality, which was mostly significant in normal gestational weight newborns.

Late-onset sepsis caused by Leclercia adecarboxylata in a preterm neonate: case report and literature review / 中华围产医学杂志

Objective:To summarize the clinical characteristics of neonatal late-onset sepsis (LOS) caused by Leclercia adecarboxylata, and provide evidence for its diagnosis and treatment. Methods:We report a case of Leclercia adecarboxylata induced LOS in a male preterm neonate diagnosed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) at the Affiliated Suzhou Hospital of Nanjing Medical University. Relavant literature was retrieved from Wanfang, VIP, CNKI, and PubMed databases up to April 2021, using terms including "neonate" "sepsis" and " Leclercia adecarboxylata". Results:The patient presented with dyspnea immediately after birth with gestational age of 34 +3 weeks and birth weight of 2 050 g. After admission at 14 min after birth, he was incubated at temperature of 33-35 ℃ and humidity of 50%-60% and received active treatment, consisting of nasal continuous positive airway pressure, tracheal intubation, intratracheal injection of pulmonary surfactant, invasive mechanical ventilation, and anti-infective treatment with piperacillin, cefoperazone/sulbactam, and meropenem. However, the patient developed LOS on day 11 of life and eventually died of disseminated intravascular coagulation and multiple organs failure despite volume expansion, anti-infective therapy, and respiratory support. The blood culture was positive for Gram-negative rod and confirmed as a multi-drug resistant strain of Leclercia adecarboxylata. Two cases of LOS caused by sensitive strain of Leclercia adecarboxylata in premature female infants were retrieved in the literature with atypical symptoms, of whom one was successfully treated and one died after active treatment. Conclusions:Leclercia adecarboxylata infection alone can lead to LOS in preterm infants without typical manifestations. MALDI-TOF MS is helpful for the diagnosis and rational application of antibiotics.

Tipos de carbapenemasas expresadas en Klebsiella spp, y Pseudomonas aeruginosa resistente a carbapenémicos en seis hospitales de alta complejidad de la Ciudad de Bogotá - Colombia / Carbapenemases produced in Klebsiella spp, and Pseudomonas aeruginosa in six hospitals in Bogotá - Colombia

INTRODUCCIÓN: En las últimas décadas, se ha incrementado la prevalencia de infecciones por bacilos gramnegativos resistentes a carbapenémicos. OBJETIVO: Determinar los tipos y la frecuencia de las distintas carbapenemasas en aislados de Klebsiella spp. y Pseudomonas aeruginosa, en seis hospitales de alta complejidad de Bogotá-Colombia. MÉTODOS: Estudio observacional descriptivo en seis hospitales de la ciudad de Bogotá, en el período de enero de 2017 a agosto de 2018. Se realizaron RPC para genes de KPC, GES, VIM, NDM, IMP y OXA-48 en cepas de Klebsiella spp y P aeruginosa resistentes a carbapenémicos. RESULTADOS: 52 aislados de P aeruginosa amplificaron para una carbapenemasa, de los cuales 39 (75%) fueron positivos para KPC, 11 (21%) para VIM y 2 co-producciones de KPC y VIM. En cuanto a Klebsiella spp., 165 cepas amplificaron al menos para una carbapenemasa, 98% expresaron KPC y 4 aislados tuvieron co-producciones de metalo-beta-lactamasas y KPC. DISCUSIÓN: Este estudio aporta información valiosa, como el incremento de producción de KPC en P. aeruginosa y la co-producción de KPC y metalo-beta-lactamasas, locual tiene una implicancia tanto en la selección del tratamiento, las medidas de aislamiento de contacto y el pronóstico de los pacientes.

BACKGROUND: In the last decades, the prevalence of infections by carbapenem resistant gram-negative bacilli has been increased. OBJECTIVE: To determine types and frequency of the different carbapenemases in Klebsiella spp. and Pseudomonas aeruginosa, in six hospitals in Bogotá-Colombia. METHODS: Descriptive and observational study, in six hospitals in the city of Bogotá, in the period ftom January 2017 to August 2018. PCR were performed for KPC, GES, VIM, NDM, IMP and OXA-48 genes, in carbapenem resistant Klebsiella spp. and P aeruginosa. RESULTS: 52 P aeruginosa isolates amplified a carbapenemase gene, of which 39 (75%) were positive for KPC, 11 (21%) for VIM and two co-productions of KPC and VIM. Regarding Klebsiella spp. 165 strains amplified at least one carbapenemase gene, 98% expressed KPC and four isolates had co-productions of metallo-P-lactamases and KPC. DISCUSSION: This study provides valuable information, such as the increased production of KPC in P. aeruginosa información valiosa, como el incremento de producción de KPC en P. aeruginosa and the co-production of KPC plus metallobetalactamases, which has an implication both in treatment selection, isolation precautions and patient prognosisy.

Validation of a Prediction Score for Drug-Resistant Microorganisms in Community-acquired Pneumonia.

Rationale: Recommended initial empiric antimicrobial treatment covers the most common bacterial pathogens; however, community-acquired pneumonia (CAP) may be caused by microorganisms not targeted by this treatment. Developed in 2015, the PES (Pseudomonas aeruginosa, extended-spectrum ß-lactamase-producing Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus) score was developed in 2015 to predict the microbiological etiology of CAP caused by PES microorganisms.Objective: To validate the usefulness of the PES score for predicting PES microorganisms in two cohorts of patients with CAP from Valencia and Mataró.Methods: We analyzed two prospective observational cohorts of patients with CAP from Valencia and Mataró. Patients in the Mataró cohort were all admitted to an intensive care unit (ICU).Results: Of the 1,024 patients in the Valencia cohort, 505 (51%) had a microbiological etiology and 31 (6%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.81 (95% confidence interval [95% CI], 0.74-0.88). For a PES score ≥5, sensitivity, specificity, the negative and positive predictive values as well as the negative and positive likelihood ratios were 72%, 74%, 98%, 14%, 0.38, and 2.75, respectively. Of the 299 patients in the Mataró cohort, 213 (71%) had a microbiological etiology and 11 (5%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.73 (95% CI 0.61-0.86). For a PES score ≥ 5, sensitivity, specificity, the negative and positive predictive values, and the negative and positive likelihood ratios were 36%, 83%, 96%, 11%, 0.77, and 2.09, respectively. The best cutoff for patients admitted to the ICU was 4 points, which improved sensitivity to 86%. The hypothetical application of the PES score showed high rates of overtreatment in both cohorts (26% and 35%, respectively) and similar rates of undertreatment.Conclusions: The PES score showed good accuracy in predicting the risk for microorganisms that required different empirical therapy; however, its use as a single strategy for detecting noncore pathogens could lead to high rates of overtreatment. Given its high negative predictive value, the PES score may be used as a first step of a wider strategy that includes subsequent advanced diagnostic tests.

[Clinical characteristics of carbapenem-resistant Enterobacteriaceae infection in pediatric liver transplantation recipients].

Objective: To explore the clinical features and treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in pediatric liver transplantation recipients and discuss the significance of CRE colonization by screening with rectal swabs. Methods: A total of 286 cases of pediatic liver transplantation recipients, who came from Tianjin First Central Hospital during August 1,2017 to August 1, 2018, were retrospectively investigated. The clinical characteristics, antibiotic susceptibity test, treatment outcomes and prognosis of CRE infection patients were analyzed. CRE colonization were screened by rectal swabs after liver transplantation. All cases were divided into CRE colonization group and non-CRE colonization group based on CRE colonization results. The high risk factors of CRE colonization and its relationship with CRE infection were investigated. χ(2) test was used for the comparison between groups.The single-factor analysis was used to screen risk factors. Results: The 286 cases included 132 male and 154 female cases. The age was (8±4) months.CRE infection rate after liver transplantation was 7.3% (21/286). The time of CRE infection was the 5(th) (1(th)-14(th)) days after transplantation. Abdominal infection was the most common (95.2%, 20/21), followed by bloodstream infection (12 cases) and pulmonary infection (8 cases). Infection in two or more sites accounted for 71.4% (15/21); 27 CRE strains, in which 24 strains were carbapenem-resistant Klebsiella pneumonia (88.9%), 2 strains were carbapenem-resistant Escherichia coli (7.4%) and one strain was carbapenem-resistant Enterobacter aerogenes (3.7%). The drug resistance rate of CRE strains to carbapenems, penicillin antibiotics, second-and third-generation cephalosporin was 100.0%. Medication treatment included meropenem+fosfomycin (13 cases) and meropenem+tegacycline (8 cases). The treatment was effective in 16 cases and the time was 19 (1-27) d. The 1-year survival rate among CRE infection group and non-CRE infection group were 71.4% (15/21) and 98.1% (260/265), respectively (χ(2)=37.460, P<0.01). CRE infection rate among CRE colonization group and non-CRE colonization group were 26.4% (19/72) and 0.9% (2/214), respectively (χ(2)=51.300, P<0.01). Factors before transplantation, including third-generation cephalosporin or carbapenems exposure, prolonged hospital stay within 3 months, CRE infection, and factors after transplantation, including emergency surgery, mechanical ventilation more than 24 hours (χ(2)=20.570, 6.411, 13.960, 14.600, 9.560, all P<0.01) were high risk factors for CRE colonization. Conclusions: The prognosis of CRE infection after pediatric liver transplantation is poor. Timely diagnosis and treatment are of great importance. Much attention should be paid on CRE rectal colonization and its risk factors. Screening of CRE colonization is important for early warning and control of CRE infection.

[Urinary Tract Infections Caused by Community-Acquired Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae in a Level III Hospital - A Retrospective Study]. / Infeções Urinárias Causadas por Enterobacteriaceae Produtoras de ß-Lactamases de Espetro Expandido Adquiridas na Comunidade num Hospital de Nível III - Um Estudo Retrospetivo.

INTRODUCTION: The emergence of ß-lactamases producing bacteria is a problem worldwide, with increasing importance in communityacquired infections, especially in urinary tract infections. Data regarding the use of non-carbapenem antimicrobials in these infections are scarce. The aim of this study was to analyse the treatment and outcome of urinary tract infections caused by community-acquired ß-lactamase-producing bacteria in children. MATERIAL AND METHODS: Retrospective study performed in a level III paediatric hospital, between June 2007 and December 2017. All children with ß-lactamase-producing Enterobacteriaceae identified in aseptically collected urine culture were included. RESULTS: A total of 175 urinary infections caused by ß-lactamases producing bacteria were diagnosed, 34 (19%) were community-acquired: 25 Escherichia coli (74%), 4 Klebsiella pneumoniae (12%), 4 Proteus mirabilis (12%) and 1 Proteus vulgaris (3%). In 30 (88%) cases, it was the first urinary infection. After identification of the microorganism and antimicrobial susceptibility, 33 (97%) children were re-evaluated and 24 (71%) had a repeat urine culture, which was positive in three (13%). In six (18%) cases, antibiotic treatment was modified. Four (12%) children had another UTI in the following month. In 30 (88%) children, imaging was carried out, with no nephrourological malformations detected. DISCUSSION: In the last decade, about 20% of urinary infections caused by ß-lactamase-producing Enterobacteriaceae were community-acquired with a relatively stable number of cases over the years. No nephro-urological malformations were identified in these children. CONCLUSION: Although the number of cases is small, the clinical and microbiological outcomes showed that most were successfully treated with non-carbapenem antibiotics, with low recurrence of new episodes of urinary tract infections.

Introdução: A emergência de bactérias produtoras de ß-lactamases de espetro expandido é um problema mundial, com importância crescente nas infeções adquiridas na comunidade, nomeadamente nas infeções urinárias. Os dados pediátricos de utilização de antimicrobianos não carbapenemos nestas infeções são escassos. O objetivo do estudo foi analisar a terapêutica antibiótica instituída nas infeções urinárias causadas por estes agentes, assim como a evolução clínica e laboratorial.Material e Métodos: Estudo retrospetivo efetuado num hospital pediátrico entre junho de 2007 e dezembro de 2017. Foram incluídas todas as crianças com urocultura positiva para Enterobacteriaceae produtoras de ß-lactamases.Resultados: Foram diagnosticadas 175 infeções urinárias causadas por Enterobacteriaceae produtoras de ß-lactamases, das quais 34 (19%) foram adquiridas na comunidade: 25 Escherichia coli (74%), 4 Klebsiella pneumoniae (12%), 4 Proteus mirabilis (12%) e 1 Proteus vulgaris (3%). Em 30 (88%) episódios tratou-se da primeira infeção urinária. Após conhecimento do microrganismo e suas suscetibilidades, 33 (97%) crianças foram reavaliadas e 24 (71%) repetiram urocultura, que foi positiva em três (13%). Em seis (18%) casos foi alterado o antimicrobiano. No mês subsequente, quatro (12%) crianças tiveram nova infeção urinária e 30 (88%) crianças realizaram investigação imagiológica, sem deteção de malformações nefro-urológicas.Discussão: Na última década, cerca de 20% das infeções urinárias causadas por Enterobacteriaceae produtoras de ß-lactamases foram adquiridas na comunidade, com um número relativamente estável ao longo dos anos. Estas crianças não apresentavam malformações nefro-urológicas.Conclusão: Embora o número de casos seja pequeno, a evolução clínica e microbiológica mostrou que a maioria foi tratada com sucesso com antimicrobianos não carbapenemos, com baixa ocorrência de novos episódios.

A Case of Plesiomonas Bacteremia Without Reported Freshwater Exposure.

Introduction: Plesiomonas shigelloides is a member of the Enterobacteriaceae family generally found in freshwater. There is little substantive data about the prevalence or distribution of Plesiomonas within the United States. Plesiomonas are most commonly associated with mild, self-limited watery diarrhea among healthy individuals followed by infective colitis. Bacteremia is the most common extraintestinal manifestation of Plesiomonas. Few cases of Plesiomonas bacteremia can be found in the literature. Clinical Findings: An elderly female with multiple comorbidities was admitted to our hospital for evaluation of generalized cramping abdominal pain of several days duration. She denied any freshwater or saltwater exposure. The patient's labs were significant for leukocytosis and lactic acidosis. An abdominopelvic CT showed acute colitis of the descending colon. Outcomes: Surgery was consulted for suspicion of ischemic colitis, and the patient subsequently underwent subtotal colectomy, splenectomy and resection of the distal small bowel with an ileostomy, as extensive necrotic bowel was found. Blood cultures taken on admission grew Plesiomonas shigelloides, for which piperacillin-tazobactam was started. Negative blood cultures were obtained 4 days after positive blood cultures. Conclusions: Relative rarity and variability of presentation, presence or absence of underlying disease or exposure to risk factors, and currently limited data utilizing different antimicrobial regimens contribute to the difficulty in outlining guideline-based regimens for management of Plesiomonas.

The Clinical and Molecular Epidemiology of CTX-M-9 Group Producing Enterobacteriaceae Infections in Children.

INTRODUCTION: The pandemic of extended-spectrum beta-lactamase-(ESBL)-producing Enterobacteriaceae (Ent) is strongly linked to the dissemination of CTX-M-type-ESBL-Ent. We sought to define the epidemiology of infections in children due to an emerging resistance type, CTX-M-9-group-producing-Ent (CTX-M-9-grp-Ent). METHODS: A retrospective matched case-control analysis of children with CTX-M-9-grp-Ent infections who received medical care at three Chicago area hospitals was performed. Cases were defined as children possessing extended-spectrum cephalosporin-resistant (ESC-R) infections due to blaCTX-M-9. PCR and DNA analysis assessed beta-lactamase (bla) genes, multi-locus sequence types (MLST) and phylogenetic grouping of E. coli. Controls were children with ESC-susceptible (ESC-S)-Ent infections matched one case to three controls by age, source, and hospital. The clinical-epidemiologic predictors of CTX-M-9-grp-Ent infection were assessed. RESULTS: Of 356 ESC-R-Ent isolates from children (median age 4.1 years), the CTX-M-9-group was the solely detected bla gene in 44 (12.4%). The predominant species was E. coli (91%) of virulent phylogroups D (60%) and B2 (40%). MLST revealed multiple strain types. On multivariable analysis, CTX-M-9-grp-Ent occurred more often in E. coli than other Ent genera (OR 7.4, 95% CI 2.4, 27.2), children of non-Black-White-Hispanic race (OR 7.4, 95% CI 2.4, 28.2), and outpatients (OR 4.5, 95% CI 1.7, 12.3), which was a very unexpected finding for infections due to antibiotic-resistant bacteria. Residents of South Chicago had a 6.7 times higher odds of having CTX-M-9-grp-Ent infections than those in the reference region (West), while residence in Northwestern Chicago was associated with an 81% decreased odds of infection. Other demographic, comorbidity, invasive-device, and antibiotic use differences were not found. CONCLUSION: CTX-M-9-grp-Ent infection may be associated with patient residence and is occurring in children without traditional in-patient exposure risk factors. This suggests that among children, the community environment may be a key contributor in the spread of these resistant pathogens.

Impacto clínico del desescalamiento a ertapenem en pacientes críticos con infecciones por Enterobacteriaceae / Clinical impact of ertapenem de-escalation in critically-ill patients with Enterobacteriaceae infections

Resumen Introducción: Ertapenem ha demostrado eficacia frente a Enterobacteriaceae productoras de β-lactamasas de espectro extendido, pero carece de actividad contra bacterias no fermentadoras; el desescalamiento a este antimicrobiano cuando no existe la presencia de P. aeruginosa podría reducir la presión selectiva contra esta bacteria y mejorar los resultados clínicos. Objetivo: Evaluar el impacto clínico del desescalamiento de antimicrobianos con cobertura anti-pseudomonas a ertapenem, un agente sin este espectro, en pacientes críticos con infecciones por Enterobacteriaceae. Métodos: Se realizó un estudio de cohorte prospectivo en adultos admitidos a Unidades de Cuidado Intensivo (UCI) con infecciones por Enterobacteriaceae, que habían sido desescalados de una cobertura anti-pseudomonas, a un antimicrobiano sin la misma (ertapenem). Se realizó un modelo de riesgo proporcional de Cox comparando mortalidad por cualquier causa y duración de estancia hospitalaria entre aquellos pacientes que permanecieron con cobertura anti-pseudomonas versus aquellos que fueron desescalados a ertapenem. Resultados: 105 pacientes en el grupo anti-pseudomonas fueron comparados con 148 pacientes del grupo de desescalamiento a ertapenem. El desescalamiento estuvo asociado con una menor mortalidad por cualquier causa comparado con los pacientes que permanecieron con cobertura anti-pseudomonas (hazard ratio ajustado 0,24; IC 95%: 0,12-0,46). La estancia hospitalaria en UCI fue similar en ambos grupos. Discusión: Los pacientes de UCI con infecciones por Enterobacteriaceae desescalados a terapia con ertapenem, tuvieron mejores resultados clínicos comparados con aquellos que permanecieron en terapia anti-pseudomonas, sugiriendo que el desescalamiento es una práctica segura en esta población.

Background: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. Aim: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. Methods: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. Results: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. Discussion: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.

Risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae infection causing septic shock in cancer patients with chemotherapy-induced febrile neutropenia.

Patients with chemotherapy-induced febrile neutropenia (FN) are vulnerable to extended-spectrum b-lactamase-producing Enterobacteriaceae (ESBL-PE) infection. Early identification of patients suspected to have ESBL-PE infection for empirical carbapenem administration is crucial; nevertheless, risk factors for ESBL-PE causing septic shock remain unclear. We identify factors to predict ESBL-PE in septic shock patients with chemotherapy-induced FN. In this observational, prospectively collected registry-based study, consecutive adult chemotherapy-induced FN patients with septic shock who were admitted to the emergency department between June 2012 and June 2018 were enrolled. Clinical and laboratory data extracted from the septic shock registry were assessed to identify risk factors for ESBL-PE. Of 179 chemotherapy-induced FN septic shock patients, ESBL-PE is isolated in 23 (12.8%). ESBL-PE infection is frequently seen in patients with hepatobiliary cancer (17.4% vs. 4.5%, P = 0.037), leukemia (13.0% vs. 2.6%, P = 0.046), and those with profound neutropenia (defined as absolute neutrophil count < 100) (73.9% vs. 43.6%, P = 0.007) in contrast to those with lung cancer (0% vs. 14.7%, P = 0.048) and other solid cancer (0% vs. 19.2%, P = 0.016). Multivariate logistic regression reveals that profound neutropenia (adjusted OR 3.67; 95% CI 1.372-9.799; P = 0.010) is an independent risk factor for ESBL-PE infection after adjusting age, the presence of solid tumor, and the parameters of sepsis severity scores. ESBL-PE is rare (12.9%) in chemotherapy-induced FN patients with septic shock. Early empirical carbapenem therapy might be considered in chemotherapy-induced FN patients with profound neutropenia.

The Role of Cefepime in the Treatment of Extended-Spectrum Beta-Lactamase Infections.

OBJECTIVE: To review the efficacy of cefepime for use in infections caused by extended-spectrum beta-lactamase (ESBL)-producing organisms. DATA SOURCES: A PubMed literature search (May 2000 to June 2017) was performed using the keyword cefepime and the MeSH terms beta-lactamases, cephalosporinases, and Enterobacteriaceae infections. STUDY SELECTION AND DATA EXTRACTION: All human, English language studies evaluating cefepime use for the treatment of ESBL-producing Escherichia coli and Klebsiella pneumoniae infections were included. DATA SYNTHESIS: Studies assessing the use of cefepime for ESBL infections are few, and clinical studies are limited by design and sample size. The largest pharmacokinetic/pharmacodynamic study, a Monte Carlo simulation using data from the U.S. SENTRY antimicrobial surveillance program, evaluating cefepime use for infections due to ESBL-producing organisms found a 95% to 100% probability of target attainment with traditional cefepime dosing regimens. Most clinical studies found that patients treated with cefepime empirically and definitively had higher rates of mortality than those treated with carbapenems. However, in concordance with other studies reporting minimum inhibitory concentration (MIC) data, lower MICs were associated with lower mortality. CONCLUSIONS: Cefepime should be avoided for empiric treatment of suspected ESBL infections and should only be considered for definitive treatment if the MIC ≤1 µg/mL. However, the site and severity of infection, local resistance patterns, and patient-specific risk factors should also help guide antimicrobial selection.

Evolução da resistência bacteriana em infecção comunitária do trato urinário em idosos / Evolution of bacterial resistance in community-acquired urinary tract infection in the elderly / Evolución de la resistencia bacteriana en infección comunitaria del tracto urinario en ancianos

Justificativa e Objetivos: Infecções do trato urinário de origem comunitária em idosos são frequentes. O estudo objetivou avaliar a prevalência e a evolução da resistência das bactérias gram-negativas de infecção comunitária do trato urinário em idosos. Métodos: Estudo transversal, dividido em dois períodos 2011-2012 e 2013-2015, realizado no município de Goiânia, Goiás, de 2011 a 2015, com a participação de quatro laboratórios clínicos. Todos os relatórios positivos de urocultura com o respectivo antibiograma foram considerados. Apenas o primeiro laudo de exame de cada paciente foi incluído na análise, a menos que a reinfecção ocorra três meses após a primeira. Resultados: Foram analisados 3.388 antibiogramas. Os microrganismos mais frequentemente isolados foram sucessivamente E. coli (75,6%), K. pneumoniae (16,6%) e Proteus spp. (5,7%). E. coli apresentou alta taxa de resistência à Sulfonamida (40,5%), Ciprofloxacina (35,0%) e aumento da resistência as Cefalosporinas de 2ª Geração (p = 0,007). As maiores taxas de resistência em K. pneumoniae foram para Sulfonamida (35,2%), Nitrofurantoína (37,9%), Gemifloxacina (46,1%) e Ofloxacina (46,1%) com aumento da evolução da resistência aos carbapenems (p = 0,03) e Cefalosporinas da 1ª Geração (P = 0,049). Para Proteus spp., a maior resistência foi para Gemifloxacina (46,11%), Ofloxacina (46,11%), Nitrofurantoína (76,68%) e Levofloxacina (81,87%). Enterobacter spp., resistência à Gemifloxacina (42,9%), Ofloxacina (42,9%), Cefalosporinas da 1ª Geração (44,3%) e Levofloxacina (77,1%), com evolução da resistência à Cefalosporina de 2ª geração (p = 0,0057). Conclusão: A prevalência da resistência bacteriana foi elevada para os principais antimicrobianos testados e foi identificada tendência para o aumento da resistência entre os microrganismos analisados.(AU)

Background and Objectives: Urinary tract infections of community origin in the elderly are frequent. The study aimed to evaluate the prevalence and evolution of resistance of gram-negative bacteria to community-acquired urinary tract infection in the elderly. Methods: Cross-sectional study, divided into two periods 2011-2012 and 2013-2015, carried out in the municipality of Goiânia, Goiás, Brazil from 2011 to 2015, with the participation of four clinical laboratories. All positive uroculture reports with the respective antibiogram were considered. Only the first report of each patient was included in the analysis, unless reinfection occurred three months after the first. Results: A total of 3,388 antibiograms were analyzed. The most frequently isolated microorganisms were successively E. coli (75.6%), K. pneumoniae, (16.6%) and Proteus spp. (5.7%). E. coli showed a high resistance rate for Sulfonamide (40.5%), Ciprofloxacin (35.0%) and increased resistance to 2nd Generation Cephalosporins (p = 0.007). The highest resistance rates in K. pneumonia were to Sulfonamide (35.2%), Nitrofurantoin (37.9%), Gemifloxacin (46.1%) and Ofloxacin (46.1%) with Increase in resistance evolution to Carbapenems (p = 0.03) and Cephalosporins of the 1st Generation (p = 0.049). For Proteus spp., the highest resistance were to Gemifloxacin (46.11%), Ofloxacin (46.11%), Nitrofurantoin (76.68%) and Levofloxacin (81.87%). Enterobacter spp., had greater resistance to Gemifloxacin (42.9%), Ofloxacin (42.9%), 1st Generation Cephalosporins (44.3%) and Levofloxacin (77.1%), with evolution of resistance to 2nd Generation Cephalosporin (p = 0.0057). Conclusion: The prevalence of bacterial resistance was high for the main antimicrobials tested and a trend was identified for the increase of resistance among the analyzed microorganisms.(AU)

Justificación y objetivos: Las infecciones del tracto urinario de origen comunitario en ancianos son frecuentes. El estudio objetivó evaluar la prevalencia y la evolución de la resistencia de las bacterias gram-negativas de infección comunitaria del tracto urinario en ancianos. Métodos: Estudio transversal, dividido en dos períodos 2011-2012 y 2013-2015, realizado en el municipio de Goiânia, Goiás, Brasil, de 2011 a 2016, con la participación de cuatro laboratorios clínicos. Se consideraron todos los informes positivos de urocultura con el respectivo antibiograma. Sólo el primer laudo de examen de cada paciente fue incluido en el análisis, a menos que la reinfección ocurrió tres meses después de la primera. Resultados: Un total de 3388 antibiogramas fueron analizados. Los microorganismos más frecuentemente aislados fueron sucesivamente E. coli (75,6%), K. pneumoniae (16,6%) y Proteus spp. (5,7%). E. coli presentó alta tasa de resistencia a la Sulfonamida (40,5%), Ciprofloxacino (35,0%) y aumento de la resistencia a las Cefalosporinas de segunda generación (p = 0,007). Las mayores tasas de resistencia en K. pneumoniae fueron para la Sulfonamida (35,2%), la Nitrofurantoína (37,9%), la Gemifloxacina (46,1%) y la Ofloxacina (46,1%) con un aumento de la evolución de la resistencia a los Carbapenemas (p = 0,03) y Cefalosporinas de la 1ª Generación (P = 0,049). Para Proteus spp., La mayor resistencia fue para Gemifloxacina (46,11%), Ofloxacina (46,11%), Nitrofurantoína (76,68%) y Levofloxacina (81,87%). Enterobacter spp., Las mayores tasas de resistencia fueron para a la Gemifloxacina era (42,9%), Ofloxacina (42,9%) de las Cefalosporinas de 1ª generación (44,3%) y Levofloxacina (77,1%), un aumento de la resistencia a la Cefalosporina 2ª generación (p = 0,0057). Conclusión: La prevalencia de la resistencia bacteriana fue elevada para los principales antimicrobianos probados y se identificó una tendencia al aumento de la resistencia entre los microorganismos analizados.(AU)

Identificación de genes de resistencia a carbapenémicos en enterobacterias de hospitales de Perú, 2013-2017 / Identification of carbapenem-resistant genes in enterobacteria from peruvian hospitals, 2013-2017

RESUMEN La diseminación global de carbapenemasas es de importancia en la salud pública. El objetivo del estudio es describir la presencia de genes de resistencia a carbapenémicos tipo KPC y metalobetalactamasas en enterobacterias aisladas de 12 hospitales y remitidos al Laboratorio de Referencia Nacional de Infecciones Intrahospitalarias del Instituto Nacional de Salud de Perú durante los años 2013 al 2017. Las cepas fueron identificadas por métodos convencionales, la resistencia antimicrobiana fue determinada por métodos fenotípicos, bioquímicos y la presencia de genes de resistencia, se detectaron por PCR convencional. Se identificaron 83 cepas con carbapenemasas: 26 (31,3 %) portando el gen blaKPC, 56 (67,5 %) el gen blaNDM y una (1,2 %) cepa con el gen blaIMP. Es el primer reporte que da a conocer los genes de carbapenemasas circulantes en hospitales de Perú, por lo que se requiere mejorar la vigilancia para tener un mejor conocimiento de la situación en Perú.

ABSTRACT The global spread of carbapenemases is a significant public health concern. The aim of this report is to describe the presence of KPC-type carbapenem-resistant genes and enterobacteria isolated in 12 hospitals and forwarded to the Peruvian National Institute of Health's National Infection Reference Laboratory during the period between 2013 and 2017. The strains were identified by conventional methods; antimicrobial resistance was determined by phenotypic and biochemical methods. The presence of resistant genes was detected by conventional PCR. Eighty-three (83) strains harboring carbapenemases were identified: 26 (31.3%) carrying the blaKPC gene, 56 (67.5%) the blaNDM gene, and one strain (1.2%) with the blaIMP gene. This is the first report that shows the circulating carbapenemases genes in Hospitals in Peru of cases submitted for their confirmation to the National Reference Laboratory, so it is necessary to improve the surveillance to better understand their situation in our country.

Genome misclassification of Klebsiella variicola and Klebsiella quasipneumoniae isolated from plants, animals and humans.

OBJECTIVE: Due to the fact that K. variicola, K. quasipneumoniae and K. pneumoniae are closely related bacterial species, misclassification can occur due to mistakes either in normal biochemical tests or during submission to public databases. The objective of this work was to identify K. variicola and K. quasipneumoniae genomes misclassified in GenBank database. MATERIALS AND METHODS: Both rpoB phylogenies and average nucleotide identity (ANI) were used to identify a significant number of misclassified Klebsiella spp. genomes. RESULTS: Here we report an update of K. variicola and K. Quasipneumoniae genomes correctly classified and a list of isolated genomes obtained from humans, plants, animals and insects, described originally as K. pneumoniae or K. variicola, but known now to be misclassified. CONCLUSIONS: This work contributes to recognize the extensive presence of K. variicola and K. quasipneumoniae isolates in diverse sites and samples.

Klebsiella variicola and Klebsiella quasipneumoniae with capacity to adapt to clinical and plant settings.

OBJECTIVE: To compare the genetic determinants involved in plant colonization or virulence in the reported genomes of K. variicola, K. quasipneumoniae and K. pneumoniae. MATERIALS AND METHODS: In silico comparisons and Jaccard analysis of genomic data were used. Fimbrial genes were detected by PCR. Biological assays were performed with plant and clinical isolates. RESULTS: Plant colonization genes such as cellulases, catalases and hemagglutinins were mainly present in K. variicola genomes. Chromosomal ß-lactamases were characteristic of this species and had been previously misclassified. K. variicola and K. pneumoniae isolates produced plant hormones. CONCLUSIONS: A mosaic distribution of different virulence- and plant-associated genes was found in K. variicola and in K. quasipneumoniae genomes. Some plant colonizing genes were found mainly in K. variicola genomes. The term plantanosis is proposed for plant-borne human infections.