Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Practice of precise management of antibiotics in a children′s hospital in combination with key performance indicators / 中华医院管理杂志

Bacterial infection is the main cause of infectious diseases in children. Antibacterials play an important role in anti infection treatment of children. At present, the treatment of antimicrobial drugs in children is facing a severe situation of bacterial resistance. In January 2020, a children′s specialized hospital carried out the practice of precise management of antibiotics in combination with key performance indicators. Through the multi sectoral linkage of management and technology, eight key performance indicators and assessment methods were set up from three levels of antibiotic use, bacterial resistance and hospital infection, to standardize the clinical application of antibiotics and continue to promote the rational use of antibiotics. This practice had improved the performance indicators of antibacterial management. Among them, the use intensity of antibacterial drugs for inpatients decreased from 40.07 DDD in 2019 to 29.00 DDD in 2021, the use rate of antibacterial drugs for inpatients decreased from 81.32% to 64.40%, the percentage of antibacterial drug expenses in total drug expenses decreased from 35.41% to 26.82%, the use proportion of non restricted antibacterial drugs in antibacterial drugs increased from 71.30% to 82.21%, and the drug resistance rate of Salmonella to β-Lactam/enzyme inhibitors decreased from 4.84% to 0.03%, and the incidence of hospital infection decreased from 1.16% to 0.96%. The precise management of antibiotics in combination with key performance indicators improved the level of rational use of antibiotics, effectively curbed bacterial resistance, achieved phased results, so as to provide a reference for the scientific management of antibiotics in children′s hospitals.

Late-onset neonatal infections and bacterial multidrug resistance / Infecções neonatais tardias e multirresistência bacteriana

Abstract Objective: This study aims to describe bacterial and antimicrobial sensibilities in late-onset healthcare-associated infections (HAIs) with laboratory confirmation in a Neonatal Intensive Care Unit (NICU) of a public hospital in Ceará. Methods: This was a cross-sectional study conducted from January 2013 to December 2017. The bacterial types involved in late-onset HAIs, their sensitivity to antimicrobials, and their multidrug resistance were evaluated. The latter was classified according to the criteria revised by the Pan-American Health Organization as multidrug resistance (MDR), extended drug resistance (XDR), or pandrug resistance (PDR). The description of the variables was performed through proportions and frequency distribution depicted in tables. Results: Of the 427 patients with late-onset HAIs, 47 (11.0%) had bacterial infections confirmed by blood cultures, and 7 (14.9%) had infections caused by MDR bacteria. Among the types of bacteria, 26 (55.3%) were Gram-negative bacteria, and 21 (44.7%) were Gram-positive bacteria. Among the Gram-negative bacteria, 92.3% (n=24) showed resistance to more than one antimicrobial, especially to ampicillin (81.2%), cefepime (33.1%), gentamicin (19.4%), and piperacillin/tazobactam (17.2%). Among the MDR ones, three cases had Klebsiella pneumoniae, and three had Pseudomonas aeruginosa, classified as two MDR and one XDR, and three XDR, respectively. Gram-positive resistance to penicillin was the most common one (80.0%), and approximately half of the strains being resistant to oxacillin. Susceptibility was high to vancomycin (97.5%), but one microorganism was resistant to oxacillin and vancomycin. Conclusions: The emergence of MDR strains is a reality in NICUs, carrying the risk of therapeutic failure and requiring continuous prevention protocols aimed at minimizing the risks of contamination by bacteria with high morbidity and mortality.

RESUMO Objetivo: Descrever as bactérias e sensibilidades aos antimicrobianos nas infecções relacionadas à assistência à saúde (IRAS) tardias com confirmação laboratorial em Unidade de Terapia Intensiva Neonatal (UTIN) de um hospital público do Ceará. Métodos: Estudo transversal, de janeiro de 2013 a dezembro de 2017. Foram avaliados os tipos de bactérias das IRAS tardias, a sensibilidade aos antimicrobianos e a multirresistência. Esta foi classificada segundo os critérios revisados pela Organização Pan-Americana da Saúde como MDR, ou multirresistência (multidrug resistance); XDR, ou resistência estendida (extensively drug-resistance); ou PDR, panresistência (pandrug-resistance). A descrição das variáveis foi realizada por meio de proporções e distribuição das frequências na forma de tabelas. Resultados: Dos 427 pacientes com IRAS tardias, 47 (11,0%) apresentaram infecções bacterianas confirmadas por hemoculturas, sete (14,9%) das quais foram causadas por bactérias multirresistentes. Entre os tipos de bactérias, 26 (55,3%) foram Gram-negativas e 21 (44,7%) Gram-positivas. Entre as primeiras, 92,3% (n=24) apresentaram resistências a mais de um antimicrobiano, destacando-se ampicilina (81,2%), cefepima (33,1%), gentamicina (19,4%) e piperacilina/tazobactam (17,2%). Entre as multirresistentes, três foram Klebsiella pneumoniae e três Pseudomonas aeruginosa, classificadas como duas MDR e uma XDR, e três XDR, respectivamente. A resistência das Gram-positivas à penicilina foi a mais comum (80,0%). A susceptibilidade foi alta à vancomicina (97,5%), porém uma bactéria foi resistente à oxacilina e à vancomicina. Conclusões: O aparecimento de cepas multirresistentes é uma realidade em UTIN com risco de falha terapêutica, sendo necessários protocolos contínuos de prevenção a fim de minimizar os riscos de contaminação interpessoal e ambiental por bactérias de alta morbimortalidade.

Antibiotic indication in endodontics by Colombian dentists with different levels of training: a survey / Indicação dos antibióticos em Endodontia por dentistas colombianos com diferentes níveis de formação: uma pesquisa por questionário

ABSTRACT Aim: This study investigated how Colombian dentists with different academic levels indicate antibiotics with therapeutic purposes in endodontics. Materials and method: A cross-sectional survey was conducted among 559 dentists in the form of an online questionnaire. Results: Three hundred and twenty questionnaires were answered (57.2%). There were significant differences among respondents. For irreversible pulpitis, 140 dentists (43.7%) said they prescribe antibiotics (57.5% of general practitioners, 20.1% of specialists and 38.9% of those with Master's and/or PhD degrees), while for symptomatic apical periodontitis, 183 (57.2%) did so (74.1% of general practitioners, 28.4% of specialists and 50.0% of those with Master's and/or PhD degrees) (p < 0.05). Amoxicillin was the most frequently prescribed antibiotic, and its association with clavulanic acid was the most often cited for acute periradicular abscess with systemic involvement. Conclusions: The greatest misunderstandings in prescribing antibiotics occurred among general practitioners. Considering all clinical conditions that do not require antibiotics, 60% of general practitioners and 34% of specialists, on average, indicated antibiotics.

RESUMO Objetivo: Este estudo investigou como dentistas colombianos com diferentes níveis acadêmicos indicaram antibióticos com fins terapêuticos em Endodontia. Materiais e método: Realizou-se um levantamento transversal com 559 dentistas. Foi enviado um questionário online. Resultados: Foram respondidos 320 questionários (57,2%). Houve diferenças significativas entre os profissionais com diferentes níveis de formação. Para pulpite irreversível, 140 (43,7%) dentistas afirmaram indicar antibióticos (57,5% clínicos gerais, 20,1% especialistas e 38,9% com mestrado e/ou doutorado), enquanto para periodontite apical sintomática, 183 (57,2%) prescrevem estes medicamentos (74,1% clínicos, 28,4% especialistas e 50,0% com mestrado e doutorado) (p < 0,05). A amoxicilina foi a mais indicada entre os profissionais, e sua associação com ácido clavulânico foi a mais referida para abscesso perirradicular agudo com acometimento sistêmico. Conclusões: Os maiores equívocos na prescrição de antibióticos ocorreram com os clínicos gerais. Considerando todas as condições clínicas que não requerem antibióticos, 60% dos clínicos gerais e 34% dos especialistas, em média, indicaram estes medicamentos.

Antibiotic Resistance Pattern in Pediatric Deep Neck Space Infection

Abstract Introduction Neck space infection in the pediatric age group is common but can be life-threatening if not diagnosed properly. Since it is a polymicrobial disease, antibiotic usage should be guided by culture sensitivity pattern. Objectives To assess the microbiology, antibiotic resistance pattern and the outcome of the medical and surgical management of deep neck space infection in children. Methods This was a prospective study of children admitted for management of neck space infection from August 2017 to August 2018. The age, gender, organisms isolated, sensitivity and resistance to antibiotics, length of hospital stay, complications, and recurrence were noted. The descriptive data were analyzed. Results Out of 108 cases, there were 51 males (47.2%) and 57 females (52.8%) ranging from 1 month to 15 years, with a mean age of 5.32 +/- 4.35 years. The mean period of hospitalization was 6.98 days. Staphylococcus aureus was the most common organism isolated with less coagulase-negative staphylococci and streptococci. Clindamycin was the most sensitive drug (82.35%) followed by vancomycin and cloxcillin, while amoxicillin/ampicillin, a commonly used drug, was the least sensitive (20.58%). The abscess recurrence rate was 9.28%. The outcomes of either medical treatment or a combined medical or surgical treatment in properly selected cases were comparable. Conclusion Clindamycin or cloxacillin can be used as a first-line option for neck infection in children. Ampicillin/amoxicillin alone has a small role in neck abscess because of high resistance to this type of antibiotic.

Perfil antibiótico de estreptococos del grupo viridans aislados de cavidad oral en individuos con uso prolongado de antibióticos / Antibiotic profile of viridans streptococci group isolated of oral cavity from patients with prolonged use of antibiotics

RESUMEN Los estreptococos del grupo viridans (EGV) son un grupo heterogéneo de bacterias saprófitas anaerobias facultativas que forman parte de la flora normal de cavidad oral. El incremento de la resistencia antibiótica de este grupo de bacterias cobra importancia en pacientes hospitalizados con terapia antibiótica prolongada, en los cuales estos microorganismos pueden ser sustituidos por bacterias multirresistentes. Objetivos: Determinar el porcentaje de cepas de EGV aisladas de cavidad oral resistentes a los antibióticos utilizados en el tratamiento de diversas patologías infecciosas hospitalarias. Material y Métodos: Estudio observacional descriptivo en el que se incluyeron 60 pacientes hospitalizados con historia de terapia antibiótica por más de 3 semanas. Las muestras se procesaron siguiendo protocolos estandarizados de recolección, aislamiento e identificación para EGV de cavidad oral y un protocolo de pruebas de sensibilidad antibiótica. Los resultados se muestran en tablas y gráficas de frecuencia. Resultados: La principal indicación para terapia antibiótica intrahospitalaria fue infección orofacial: 28,33%. La penicilina fue el antibiótico más utilizado ya sea en terapia única, combinada o múltiple en todos los pacientes. Se aislaron en total 108 cepas de EGV, con un promedio de 1,8 cepas por paciente. La especie predominantemente identificada fue S. mutans. El 96,3% de las cepas de EGV fue sensible a todos los antibióticos incluidos en el panel. Conclusiones: El uso de distintas combinaciones y modalidades de terapia antibiótica no tiene efecto en la susceptibilidad de EGV aislados de cavidad oral en pacientes hospitalizados, independiente de la duración del tratamiento.

ABSTRACT Viridans group streptococci (VGS) are a heterogeneous group of saprophytic facultative anaerobic bacteria that are part of the normal flora of the oral cavity. The increased resistance to multiple antibiotics in this group of bacteria becomes important in prolonged antibiotic therapies inpatient where these common microorganisms are replaced by multi-resistant bacteria. Objectives: To determine the percentage of VGS strains isolated from oral cavity resistant to antibiotics used in hospital infectious diseases. Material and methods: This is a descriptive cross-sectional study that included 60 hospitalized patients with a history of antibiotic therapy for more than 3 weeks. The samples were processed following standardized protocols for collection, isolation and identification of oral cavity VGS and a protocol of antibiotic susceptibility testing. The results are shown in tables and graphics of absolute and relative frequencies. Results: The main indication for antibiotic therapy was orofacial infection with a 28.33%. Penicillin was the antibiotic further used either in single, combined or multiple therapies in all patients. A total of 108 samples (1.8 per patient swabs) were collected. The predominantly identified specie was Streptococcus mutans. The 96.3% of all VGS strains were sensitive to all antibiotics included in the panel. Conclusion: Using different combinations and types of antibiotic therapy inpatient has no effect on the susceptibility of VGS isolated from oral cavity separate from treatment.

Caracterización molecular de carbapenemasas en bacilos gramnegativos circulantes en hospitales de Paraguay. Primer cuatrimestre 2021 / Molecular characterization of carbapenemases in Gram-negative bacilli circulating in hospitals of Paraguay. First quarter of 2021

La resistencia a los antimicrobianos (RAM), representa un grave problema por el uso indiscriminado de antimicrobianos de amplio espectro. En nuestro país, durante el primer cuatrimestre del año, se observó un aumento inusual en el número de aislamiento de gérmenes multirresistentes, sobre todo de bacilos gramnegativos, los cuales fueron remitidos al laboratorio de referencia con el objetivo de caracterizar los genes de resistencia a los carbapenemes. Estudio observacional y prospectivo de corte transversal en 456 aislamientos de bacilos gramnegativos provenientes de 11 centros colaboradores de la Red Nacional de Vigilancia de la RAM, remitidos al Laboratorio Central de Salud Pública entre enero y abril de 2021, para la detección molecular (reacción en cadena de la polimerasa múltiple) de los genes de resistencia enzimática bla OXA-51, bla OXA-23, bla OXA-24, bla OXA-48, bla OXA-58, bla NDM, bla KPC, bla IMP, bla VIM. Trescientos sesenta correspondieron a bacilos gramnegativos no fermentadores: 346 Acinetobacter baumannii y 14 Pseudomonas aeruginosa; 96 fueron miembros de Enterobacterales, siendo prevalente Klebsiella pneumoniae (81). Todos los aislamientos de Acinetobacter baumannii resultaron ser productores de carbapenemasas: OXA-23 (94%), NDM (4%), NMD+OXA-58 (2%); en Pseudomonas aeruginosa, 7 de los 14 aislamientos (50%) fueron portadores de metalobetalactamasa del genotipo NDM (100%). Los genotipos NDM (92%) y KPC (8%) fueron confirmados en Enterobacterales. La resistencia plasmídica a carbapenemes es endémica en nuestro país, siendo prevalentes los genotipos OXA-23 en Acinetobacter baumannii y NDM en Pseudomonas aeruginosa y Enterobacterales

Antimicrobial resistance (AMR) represents a serious problem due to the indiscriminate use of broad-spectrum antimicrobials. During the first quarter of the year, an unusual increase in the number of isolation multi-resistant germs, especially gram-negative bacilli was observed, specially of Gram-negative bacilli which were referred to the reference laboratory in order to characterize the carbapenems resistance genes. Observational and prospective cross-sectional study in 456 isolates of Gram-negative bacilli from 11 collaborating centers of the National AMR Surveillance Network, referred to the Central Public Health Laboratory (LCSP) between January and April 2021, for molecular detection (multiple polymerase chain reaction) targeting the enzymatic resistance genes: bla OXA-51, bla OXA-23, bla OXA-24, bla OXA-48, bla OXA-58, bla NDM, bla KPC, bla IMP, bla VIM. Of the 456 isolates studied, 360 corresponded to non-fermenting Gram-negative bacilli, of which 346 were confirmed as Acinetobacter baumannii and 14 Pseudomonas aeruginosa; 96 were Enterobacterales, being Klebsiella pneumoniae (81) the most prevalent. All isolates of Acinetobacter baumannii carried genes encoding carbapenemases, being the OXA-23 (94%) followed by NDM (4%) and NDM +OXA-58 (2%). In Pseudomonas aeruginosa strains, 7 of the 14 isolates (50%) were carriers of NDM metallobetalactamase (100%). No carbapenemase gene was detected in the remaining 7. In all Enterobacterales strains, the presence of carbapenemases of the NDM (92%) and KPC (8%) genotypes were confirmed. Plasmid resistance to carbapenems is endemic in our country, being the OXA-23 genotypes prevalent in Acinetobacter baumannii and NDM in Pseudomonas aeruginosa and Enterobacterales

Elevada proporción de Staphylococcus aureus meticilino resistentes aislados en pacientes atendidos en un servicio ambulatorio dermatológico de referencia nacional: cohorte 2010 a 2019 / High proportion of isolated resistant methicillin-resistant Staphylococcus aureus in patients treated in a national refe rence dermatological outpatient service: cohort 2010 to 2019

Resumen Objetivo: Estimar la resistencia del Staphylococcus aureus frente a diferentes antibióticos usados para el manejo ambulatorio de piodermias. Métodos: Se realizaron análisis descriptivos y de tendencias mediante modelos de regresión segmentada. Resultados: La mayor resistencia se presentó a la oxacilina, con mediana de 54,3% (RIQ: 43 - 58,8), seguido de eritromicina con el 20%, (RIQ: 15,4 - 26,5), clindami cina con el 14% (RIQ: 7,9 - 20), gentamicina con el 7,5% (RIQ: 0 -10), trimetoprima/sulfametoxazol (SXT) con el 5,5% (RIQ: 4 - 11), y ciprofloxacina con 2,1% (RIQ: 2 - 8.4). La tendencia de la resistencia del S. aureus a la oxacilina fue creciente con un cambio anual porcentual no significativo de (0,07) (IC 95%: -3,7; 3,9). Para eritromicina, clindamicina, ciprofloxacina, trimetoprima/sulfametoxazol, y gentamicina hubo decrecimiento. Conclusiones: La resistencia del S. aureus a oxacilina fue ligeramente creciente para el periodo 2010 al 2019 y francamente creciente en los últimos 3 años, superando en promedio a lo reportado a nivel país y Latinoamérica. Los antibióticos con menor resistencia fueron ciprofloxacina, SXT, clindamicina para uso sistémico, y ácido fusídico, mupirocina para manejo tópico y descolonización. Es pertinente articular la vigilancia del S. aureus en la atención ambulatoria a la red de vigilancia nacional.

Abstract Objective: To estimate the resistance trend of Staphylococcus aureus (S. aureus) against different antibiotics in a reference dermatology outpatient center in Colombia. Methods: Descriptive and trend analyzes were performed using segmented regression models for the period 2010 to 2019. Results: The greatest resistance was presented to oxacillin, with a median of 54.3% (RIQ: 43 - 58.8), followed by erythromycin with 20%, (RIQ: 15.4 - 26.5), then clindamycin with 14% (RIQ: 7.9 - 20), gentamicin with 7.5% (RIQ: 0 -10), trimethoprim / sulfamethoxazole (SXT) with 5.5% (RIQ: 4 - 11), and ciprofloxacin with 2.1% (RIQ: 2 - 8.4). The trend of S. aureus resistance to oxacillin from 2010 to 2019 was increasing with a non-significant Annual Percent Change (APC) of (0.07) (95% CI -3.7, 3.9). APC for erythromycin (-1.2) (95% CI: -11.3; 10), clindamycin (-1.7) (95% CI: 11; -12.9), ciprofloxacin (-25.4) (95% CI: -44.6; 0.5) and trimethoprim / sul famethoxazole (-20.7) (95% CI: -43.5; 11.2), were decreasing not significant. For gentamicin the trend was decreasing and significant (-44.2) (95% CI: -19.9; -61.1). Conclusions: The resistance of S. aureus to oxacillin exhibited a slightly increasing trend for the period 2010 to 2019 and increasing in the last 3 years, exceeding on average that reported at the country level and the world average. Antibiotics for outpatient management of skin and soft tissue pyoderma with less resistance were ciprofloxacin, SXT, clindamycin for systemic use, and fusidic acid, mupirocin for topical management and decolonization. It is important to articulate surveillance of S. aureus in outpatient care to the national surveillance network.

Caracterización de Escherichia coli D7111 productora de ß-LACTAMASA TEM-176 / Characterization of Escherichia coli D7111 producing the ß-LACTAMASA TEM-176

RESUMEN El presente reporte es la descripción original de bla TEM-176. Se caracterizaron los mecanismos de resistencia a antimicrobianos de un aislamiento de Escherichia coli enterotoxigénica, determinándose la resistencia a 22 antimicrobianos categorizados en 15 grupos diferentes mediante difusión en agar, estableciéndose grupo filogenético, mecanismos de resistencia y presencia de integrones de Clase 1 y 2 mediante PCR. Integrones y genes de resistencia a β-lactámicos fueron secuenciados. El aislamiento del grupo filogenético A, mostró resistencia o sensibilidad disminuida a ampicilina, amoxicilina más ácido clavulánico, ácido nalidíxico, ciprofloxacino, estreptomicina, kanamicina, tetraciclina, trimetoprim, sulfisoxazol, cotrimoxazol, azitromicina y nitrofurantoina, detectándose la presencia de bla TEM, aadA1/2, aphA1, sul3, tet(A) y un integron de Clase 2 conteniendo un gen dfrA1. La resistencia a quinolonas se relacionó con la substitución Ser83Ala. La secuencia de TEM mostró la substitución Ala222Val, la cual a la fecha no había sido descrita, reportándose como una nueva β-lactamasa, con el nombre de bla TEM-176.

ABSTRACT The present report is the original description of bla TEM-176. The mechanisms of resistance to antimicrobial agents were determined in an enterotoxigenic Escherichia coli, determining the susceptibility to 22 antimicrobials classified in 15 different groups by agar diffusion and establishing the phylogenetic group, mechanisms of resistance and presence of Class 1 and 2 integrons. Integrons and β-lactam resistance genes were sequenced. The isolate, belonging to phylogenetic group A, showed the presence of resistance or diminished susceptibility to a ampicillin, amoxicillin plus clavulanic acid, nalidíxic acid, ciprofloxacin, streptomycin, kanamycin, tetracycline, trimethoprim, sulfisoxazole, cotrimoxazole, azithromycin and nitrofurantoin, carrying bla TEM, aadA1/2, aphA1, sul3, tet(A) and a Class 2 integron containing a dfrA1 gene. Quinolone resistance was related to the substitution Ser83Ala. The TEM sequencing showed the presence of the new substitution Ala222Val, which led to the description of the new β-lactamase bla TEM-176.

Caracterización de Escherichia coli D7111 productora de ß-LACTAMASA TEM-176 / Characterization of Escherichia coli D7111 producing the ß-LACTAMASE TEM-176

RESUMEN El presente reporte es la descripción original de bla TEM-176. Se caracterizaron los mecanismos de resistencia a antimicrobianos de un aislamiento de Escherichia coli enterotoxigénica, determinándose la resistencia a 22 antimicrobianos categorizados en 15 grupos diferentes mediante difusión en agar, estableciéndose grupo filogenético, mecanismos de resistencia y presencia de integrones de Clase 1 y 2 mediante PCR. Integrones y genes de resistencia a β-lactámicos fueron secuenciados. El aislamiento del grupo filogenético A, mostró resistencia o sensibilidad disminuida a ampicilina, amoxicilina más ácido clavulánico, ácido nalidíxico, ciprofloxacino, estreptomicina, kanamicina, tetraciclina, trimetoprim, sulfisoxazol, cotrimoxazol, azitromicina y nitrofurantoina, detectándose la presencia de bla TEM, aadA1/2, aphA1, sul3, tet(A) y un integron de Clase 2 conteniendo un gen dfrA1. La resistencia a quinolonas se relacionó con la substitución Ser83Ala. La secuencia de TEM mostró la substitución Ala222Val, la cual a la fecha no había sido descrita, reportándose como una nueva β-lactamasa, con el nombre de bla TEM-176.

ABSTRACT The present report is the original description of bla TEM-176. The mechanisms of resistance to antimicrobial agents were determined in an enterotoxigenic Escherichia coli, determining the susceptibility to 22 antimicrobials classified in 15 different groups by agar diffusion and establishing the phylogenetic group, mechanisms of resistance and presence of Class 1 and 2 integrons. Integrons and β-lactam resistance genes were sequenced. The isolate, belonging to phylogenetic group A, showed the presence of resistance or diminished susceptibility to a ampicillin, amoxicillin plus clavulanic acid, nalidíxic acid, ciprofloxacin, streptomycin, kanamycin, tetracycline, trimethoprim, sulfisoxazole, cotrimoxazole, azithromycin and nitrofurantoin, carrying bla TEM, aadA1/2, aphA1, sul3, tet(A) and a Class 2 integron containing a dfrA1 gene. Quinolone resistance was related to the substitution Ser83Ala. The TEM sequencing showed the presence of the new substitution Ala222Val, which led to the description of the new β-lactamase bla TEM-176.

Efluentes hospitalarios como reservorio de enterobacterias productoras de betalactamasas y carbapenemasas

Con el objetivo de determinar la presencia de enterobacterias productoras de betalactamasas (bla) en muestras de efluentes hospitalarios, se realizó un estudio en dos hospitales de nivel II y III de Lima, Perú. Se identificó y caracterizó el perfil de resistencia de las bacterias aisladas mediante el sistema MicroScan para 18 antimicrobianos, y mediante PCR convencional se determinó la presencia de los genes de resistencia a betalactamasas de espectro de extendido (BLEE) (bla CTX-M, bla SHV, bla TEM, bla PER) y carbapenemasas (bla KPC , bla NDM , bla VIM , bla IMP). Se identificaron 32 aislados (20 enterobacterias y 12 bacterias gramnegativas). Todas las bacterias aisladas presentaron multirresistencia. Se halló la presencia de genes BLEE (bla TEM) y carbapenemasas (bla KPC y bla IMP) en los hospitales evaluados. La liberación de estos microorganismos a la vía pública y la falta de tratamiento de los efluentes hospitalarios podría ser un importante problema de salud pública.

The aim of this study was to determine the presence of beta-lactamase- (bla) producing Enterobacteriaceae in hospital effluent samples from two level II and III hospitals in Lima, Peru. The resistance profile of the isolated bacteria was identified and characterized using the MicroScan system for 18 antimicrobials, and the presence of extended spectrum beta-lactamases (ESBL) (blaCTX-M ,bla SHV bla TEM ,bla PER) and carbapenemases (bla KPC ,bla NDM ,bla VIM ,bla IMP) resistance genes was determined by conventional PCR. Thirty-two isolates were identified (20 Enterobacteriaceae and 12 gram-negative bacteria). All the isolated bacteria showed multidrug resistance. ESBL (bla TEM) and carbapenemase (blaKPC, blaIMP) genes were found in samples from the hospitals that we evaluated. The release of these microorganisms to public areas and the lack of treatment of the hospital effluents could be an important public health problem.

Impacto sobre la resistencia bacteriana de la revisión previa de la prescripción de antibióticos por el servicio farmacéutico en hospitales del Atlántico(Colombia) / Impact on the bacterial resistance of the previous revision of the prescription of antibiotics by the pharmaceutical service in hospitals of Atlántico (Colombia)

RESUMEN Objetivo: Determinar el impacto sobre la resistencia bacteriana de la revisión previa de la prescripción de antibióticos por parte del servicio farmacéutico en hospitales de mediana y alta complejidad del departamento del Atlántico (Colombia). Metodología: Se analizaron los valores de resistencia de bacterias Gram positivas, Enterobacterias y Gram negativos no fermentadores reportados en cinco institutos prestadores de salud (IPS) del departamento del Atlántico, en dos periodos (preintervención e intervención), de 12 meses cada uno, entre junio de 2015 y mayo de 2017. Resultados: Durante los dos periodos de estudio se identificaron 68 microorganismos en 8590 aislamientos microbiológicos provenientes de muestras de orina (40,3 %), sangre (21,7 %), tejidos (8,5 %) y otras (29,5 %). Los microorganismos aislados más frecuentemente fueron Escherichia coli (28,9 %), Staphylococcus coagulasa negativo (12,1%), Klebsiella pneumoniae (12,0 %), Pseudomonas aeruginosa (11,1 %) y Staphylococcus aureus (7,2 %). Durante los dos periodos la resistencia global osciló entre 27 y 40 %. Durante la Preintervención la resistencia osciló entre el 33 y el 39 %, mientras que durante la Intervención estuvo entre el 27 y 40 %. Al comparar los periodos de estudio solo hubo disminución significativa de la resistencia en los primeros nueve meses del periodo de intervención (p < 0.05). Conclusiones: Los valores de resistencia bacteriana reportados en el periodo de intervención fueron menores que en el periodo de preintervención. Se evidenció que la revisión previa de la prescripción por parte del servicio farmacéutico en las instituciones participantes influye en una disminución significativa de la resistencia bacteriana, pero que esta debe ser tanto continua como incremental.

ABSTRACT Objective: To determine the impact on bacterial resistance of the previous review of the prescription of antibiotics by the pharmaceutical service in medium and high complexity hospitals of the Department of Atlántico (Colombia). Methodology: Resistance values were analyzed for Gram-positive bacteria, Enterobacte-rial and non-fermenting Gram-negative bacteria reported in five health care institutions (IPS) of the Atlántico Department, in two periods (pre-intervention and intervention), of 12 months each between the months of June 2015 and May 2017. Results: During the two study periods, 68 microorganisms were identified in 8,590 microbiological isolates from urine samples (40.3 %), blood samples (21.7 %), tissues (8.5%) and others (29.5 %). The most frequently isolated microorganisms were Escherichia coli (28.9 %), Coagulase Negative Staphylococcus (12.1 %), Klebsiella pneumoniae (12.0 %), Pseudomonas aeruginosa (11.1 %) and S. aureus (7.2 %). During both periods the global resistance ranged between 27 and 40 %. During the Pre-intervention the resistance ranged between 33 and 39 %, while during the Intervention it was between 27 and 40 %. When comparing study periods, there was only significant decrease in resistance in the first nine months of the intervention period (p <0.05). Conclusions: the bacterial resistance values reported during the intervention period were lower than in the pre-intervention period. It was evidenced that the previous revision of the prescription by the pharmaceutical service in the participating institutions influences a significant decrease of the bacterial resistance; but that this must be both continuous and incremental.

Clinical Distribution and Resistant Transition of Clinical Isolated Acinetobacter Bauman in Xiangya Hospital / 现代检验医学杂志

Objective The clinical distribution and drug resistance of isolated Acinetobacter Bauman strains were retrospectively analyzed in Xiangya Hospital Central South University in 2015,and its resistant transitions in ten years were also analyzed,to provide theoretical guidance for clinical rational use of antibiotics and control of infection.Methods 534 Acinetobacter Bauman strains were collected at Xiangya Hospital in 2015,the clinical distribution characteristics and drug resistance of Acinetobacter Bauman strains were analyzed according to specimen type,department,age and drug resistance result.Meanwhile,the drug resistance situation was compared with that in 2006 and 2011.Results The isolation rate of Acinetobacer Bauman from respiratory tract specimen was 76.78％,the tolal isolation rate from ICU,respiratory department of internal medicine,neurology department of internal medicine and neurosurgery department ward was 57.87 ％,and the infection patients over the age of 61 occupied 37.83 ％.Risperidone/Shubatan showed the best antibiotic activity with the resistance rate 3.02 ％ in ten drugs,the Acinetobacter Bauman strains were resist to other nine drugs in different level,with the percent from 50.0％ to 85.0％.The drugs of tobramycin and imipenem showed the greatest growth,with the resistance rate of 1.87％ and 11.70％ in 2006 in Xiangya hospital,increased to 69.85％ and 80.53％ in 2015,respectively.The drug of levofloxacin and cefepime also showed great growth in ten years with the increase of 58.81％ and 55.98％,respectively.Conclusion The clinical isolates of Acinetobacter Bauman strains mainly derived from respiratory tract specimen,and mainly distributed in ICU,the most infection people were from the older.The resistance rate of common drugs showed a significant increase in ten years,especially for cephalosporins and carbapenems.With the increase of multiple drug resistant strains,the monitoring of drug resistance of Acinetobacter Bauman and use of antibiotics rationally should be strengthened.

Analysis of Association between Antibiotic Use and Bacterial Resistance Rate in Our Hospital during 2012-2015 / 中国药房

OBJECTIVE:To provide reference for clinical rational use of antibiotics. METHODS:The use of antibiotics in our hospital from Jan. 2012 to Dec. 2015 was analyzed,the DDDs was calculated,bacterial resistance rates over the same period was analyzed,and the relationship between them were analyzed with Pearson method. RESULTS:During 2012-2015,the top 3 antibiot-ic DDDs in our hospital were cephalosporins,macrolides and quinolones;bacterial with the top 5 detection rate was Escherichia co-li,Pseudomonas aeruginosa,Klebsiella pneumoniae,Acinetobacter Bauman and Staphylococcus aureus;the DDDs of imipenem cilastatin sodium showed a positive correlation with the resistance rate of P. aeruginosa(r=0.95,P<0.05)and the total resistance rate of Gram-negative bacteria (r=0.98,P<0.05),meropenem showed a positive correlation with the resistance rate of K. pneu-moniae(r=0.97,P<0.05),piperacillin sulbactam sodium showed a negative correlation with the resistance of P. aeruginosa(r=-0.98,P<0.05). CONCLUSIONS:DDDs is correlated with the antibiotic drug resistance rate of bacteria,which should be planned and scientific used to reduce the bacterial resistance.

Effects Evaluation of Antibacterial Drug Prescriptions Comment in Outpatient and Emergency Depart-ment of a Hospital / 中国药房

OBJECTIVE:To provide reference for rational use of antibacterial drugs in the clinic. METHODS:In retrospective study,outpatient and emergency antibacterial drugs prescriptions were randomly selected from a hospital during 2013-2014,and then analyzed statistically. DDDs of antibacterial drugs were analyzed by using DDD method. RESULTS:From 2013-2014,the ap-plication rate of antibacterial drugs in the hospital declined substantially from 13.8% to 11.9%,and the rate of irrational use dropped from 2.7% to 1.2%. The application rate of antibacterial drugs was higher in pediatric department,emergency department and urology department;drug cost per capita was higher in infectious department,nephrology department and emergency depart-ment. The application rate of antibacterial drugs in pediatric department decreased greatly in 2014,compared with 2013,maintain-ing about 40%. The application rate of antibacterial drugs in emergency department during Jan.-Sept. in 2014 was lower than corre-sponding period in 2013,and that of the hospital during Jan.-Sept. in 2014 was lower than corresponding period in 2013,but dur-ing Oct.-Dec. in 2014 was slightly higher than corresponding period in 2013. Single type of antibacterial drugs were mainly used in outpatient department,accounting for 91.50% and 90.77% of antibacterial drug prescriptions in 2013 and 2014;two-drug account-ed for 8.44% and 9.11%. The top 3 antibacterial drugs in the list of DDDs during 2013-2014 were roxithromycin,cefuroxime and cefminox. CONCLUSIONS:The use of antibacterial drugs is up to the requirements of Nation Special Rectification Actirity for Clin-ical Application of Antibacterial Drugs in 2013. The prescription comment improve the quality of antibacterial drug prescriptions and rational use index greatly in outpatient department,but the application rate of antibacterial drugs is too high in some depart-ment. There still is irrational use of antibacterial drugs.

A review of global initiatives to fight antibiotic resistance and recent antibiotics׳ discovery

Data from across the world have shown an overall decline in the antibiotic pipeline and continually rising resistance to all first-line and last-resort antibiotics. The gaps in our knowledge of existing prevalence and mechanisms of antibiotic resistance (ABR) are all too well known. Several decades of antibiotic abuse in humans, animals, and agricultural practices have created health emergency situations and huge socio-economic impact. This paper discusses key findings of the studies conducted by several national and international collaborative organizations on the current state of affairs in ABR. Alongside, a brief overview of the antibacterial agents׳ discovery in recent years approved by the US FDA is discussed.

ANTIBIOTIC RESISTANCE PATTERNS OF URINARY TRACT INFECTIONS IN A NORTHEASTERN BRAZILIAN CAPITAL

Urinary tract infection is a common problem worldwide. Its clinical characteristics and susceptibility rates of bacteria are important in determining the treatment of choice and its duration. This study assessed the frequency and susceptibility to antimicrobials of uropathogens isolated from community-acquired urinary tract infections in the city of Natal, Rio Grande do Norte State capital, northeastern Brazil, from 2007 to 2010. A total of 1,082 positive samples were evaluated; E. coli was the most prevalent pathogen (60.4%). With respect to the uropathogens susceptibility rates, the resistance of enterobacteria to ciprofloxacin and sulfamethoxazole-trimethoprim was 24.4% and 50.6%, respectively. Susceptibility was over 90% for nitrofurantoin, aminoglycosides and third-generation cephalosporins. High resistance rates of uropathogens to quinolones and sulfamethoxazole-trimethoprim draws attention to the choice of these drugs on empirical treatments, especially in patients with pyelonephritis. Given the increased resistance of community bacteria to antimicrobials, local knowledge of susceptibility rates of uropathogens is essential for therapeutic decision making regarding patients with urinary tract infections.

Investigation on the Rational Use of Antibacterial Drugs before and after Intervention of Rural Community Health Service Stations Affiliated to Our Hospital / 中国药房

OBJECTIVE:To provide reference for further promoting the rational use of antimicrobial drugs in the rural commu-nity health service stations. METHODS:4 800 prescriptions were collected from 8 community health service stations affiliated to our hospital from Jan. 1,2012 to Dec. 31,2014,the use of antimicrobial drugs in the prescriptions was statistically analyzed and the indicators were compared before and after intervention. RESULTS:The proportion of use of antimicrobial drugs in these com-munity health service stations was decreased from 52.88%in 2012 to 30.38%in 2014;the clinical diagnosis of prescription of anti-microbial drug was mainly respiratory infections;what the most used types of antibacterial drugs was cephalosporins;and the pro-portion of antimicrobial drug of irrational use was decreased from 43.50%(368/846)in 2012 to 22.84%(111/486)in 2014. CON-CLUSIONS:The combination of technique and administrative intervention is remarkable. However,the unreasonable use of antibac-terial drugs still exists. Therefore,related training should be organized,and the proportion of use of antimicrobial drugs should in-cluded in the performance appraisal to further improve the use level of antimicrobial drugs in the rural community health service sta-tions.

Analysis of Drug-resistant Bacteria Monitoring and Early Warning and Clinical Application of Antibacterial Drugs in Our Hospital in 2014 / 中国药房

OBJECTIVE:To provide reference for clinical rational drug use. METHODS:Combined with bacterial drug resis-tance monitoring data in our hospital in 2014,the varieties,the amount of antibacterial drug,DDDs and other index were analyzed retrospectively for the same period. RESULTS:The detection rate of Gram-negative bacteria (79.27%) was higher than that of Gram-positive bacteria (20.73%);the most common Gram-negative bacilli and Gram-positive cocci were Escherichia coli (38.62%) and Staphylococcus aureus (5.22%). Pseudomonas aeruginosa and Stenotrophomonas maltophilia were the most com-mon non-fermentation bacteria;Main Gram positive bacteria were most sensitive to vancomycin,tigecycline and furadantin,etc. Main Gram-negative bacteria were most sensitive to imipenem,ertapenem,etc. Top 3 antibacterial drug in the list of DDDs were Levofloxacin injection,Cefazolin injection,Cefoperazone/sodium sulbactam for injection. CONCLUSIONS:Third generation of cephalosporins are used frequently in our hospital,which is a major cause of ESBLs producing and drug resistance,bacterial drug resistance monitoring and early warning data has played a positive role on guiding reasonable application of antibacterial drug in our hospital.

Drug sensitivity analysis of Enterococcus f aecium and Enterococcus f aecalis isolates from 2011 to 2013 / 国际检验医学杂志

Objective To explore the sensitivity of Enterococcus f aecium and Enterococcus f aecalis isolated from 2011 to 2013 and provide reference for anti-infection therapy .Methods The identification and drug sensitivity test of clinical isolates were carried out by using VITEK2 Compact system .Results The ratio of Enterococcus f aecium to Enterococcus f aecalis isolates was 1 .93 and it was increasing year by year .No vancomycin ,linezolid and tigecycline resistant Enterococcus f aecium and Enterococcus f aecalis i-solates was detected .The rates of Enterococcus f aecium sensitive to quinupristin-dalfopristin and tetracycline were higher than En-terococcus f aecalis(P<0 .05) ,and the rates of Enterococcus f aecium sensitive to nitrofurantoin ,ampicillin ,penicillin G ,moxifloxa-cin ,levofloxacin and ciprofloxacin were lower than that of Enterococcus f aecalis(P<0 .05) .Conclusion The detection rates of En-terococcus was shifting to Enterococcus f aecium ,and the trends became obvious year after year .The drug sensitivity of Enterococcus f aecium and Enterococcus f aecalis is different ,and doctors should choose the proper therapy according to their specific drug resist-ance .At present ,vancomycin ,linezolid and tigecycline are preffered for the treatment against infection caused by Enterococcus f aeci-um and Enterococcus f aecalis .