Advances in researches of polymyxin resistance mechanism in Klebsiella pneumoniae / 中华检验医学杂志

In recent years, the carbapenem-resistant Klebsiella pneumoniae (CRKP) continues to significantly threaten public health. The limited therapeutic options are increasingly challenging for clinicians to reintroduce the polymyxin as last-resort drug, with the results that polymyxin resistance is not scarce in settings. The polymyxin resistance mechanism is diversified, mainly the modification of the lipopolysaccharide (LPS). In addition to phoPQ, pmrAB, crrAB and mgrB on chromosome, plasmid-carried mcr gene have been found to mediate the LPS modification. The mgrB gene variation plays an important role in polymyxin resistance. Above all, the aim of the current review is to discuss the mechanism of polymyxin resistance mechanism in Klebsiella pneumoniae provide insights for preventing this phenomenon.

Clinical practice guideline for screening of patients at risk of colonization by carbapenemase-producing Enterobacterales and the treatment of infections caused by these bacteria / Guía de práctica clínica para la tamización de pacientes con riesgo de colonización por Enterobacterales productores de carbapenemasasy el manejo de infecciones causadas por estas bacterias

Abstract Carbapenemase-producing Enterobacterales (CPE) infections have increased in recent years. Colombia has become an endemic country for this group of microorganisms, and the infections they cause have a serious impact in terms of morbidity and mortality. The early identification of CPE carriers who are admitted to health care centers as patients is necessary to implement adequate isolation and infection control measures to limit the spread of this type of microorganisms in hospitals. Furthermore, treating these infections is a challenging task due to the limited therapeutic alternatives available and the fact that there are only a few studies proving their effectiveness in this setting. Therefore, the objective of the present work is to develop a clinical practice guideline (CPG) for the screening of patients at risk of CPE colonization and the treatment of inpatients with suspected or confirmed infections caused by this type of bacteria through a CPG adaptation process based on the ADAPTE methodology. With this purpose in mind, evidence-informed recommendations for the screening and timely identification of CPE carriers admitted to hospitals are made, as well as for the adequate pharmacological treatment of CPE infections in this context.

Resumen Las infecciones por Enterobacterales productores de carbapenemasas (EPC) han aumentado en los últimos años. Colombia se ha convertido en un país endémico para este grupo de microorganismos y las infecciones que causan tienen un impacto importante en términos de morbimortalidad. La identificación temprana de los portadores de EPC que ingresan como pacientes a las instituciones de salud es necesaria para implementar medidas de aislamiento y control de infecciones adecuadas que limiten la diseminación de este tipo de microorganismos en los hospitales. Además, el tratamiento de estas infecciones es difícil debido a las limitadas alternativas terapéuticas disponibles y la escasez de estudios que demuestren su efectividad en este escenario. Por lo anterior, el objetivo del presente trabajo es desarrollar una guía de práctica clínica (GPC) para la tamización de pacientes con riesgo de colonización por EPC y para el manejo de pacientes con infecciones, ya sea sospechadas o confirmadas, causadas por este tipo de bacterias, mediante un proceso de adaptación de GPC basado en la metodología ADAPTE. Con este propósito en mente, se hacen recomendaciones informadas en evidencia para realizar la tamización y oportuna identificación de portadores de EPC admitidos en instituciones hospitalarias, así como para el adecuado manejo farmacológico de las infecciones por CPE en este escenario.

Comparative evaluation of susceptibility testing methods for colistin and polymyxin B on isolates of Enterobacteriaceae / 中华检验医学杂志

Objective:To provide a promising and optimal laboratory susceptibility-testing method for the clinical usage of antibiotic (polymyxin), four susceptibility-testing methods were performed and the broth microdilution (BMD) was chosen as the gold standard.Methods:A total number of eighty-eight nonduplicate clinical Enterobacteriaceae specimes were collected from January to December of 2019 in the First Affiliated Hospital, Fujian Medical University. Among the clinical specimens, of which six strains were positive for mcr-1. The minimal inhibitory concentration (MIC) of polymyxin of the clinical specimens were examined by the following methods: (1) broth microdilution, (2) colistin broth disk elution, (3) Vitek-2?, (4)BD PhoenixTM,(5)commercial broth microdilution. With BMD as reference, essential agreement (EA), categorical agreement(CA), very major error(VME) and major error (ME) of polymyxins for different methods were analyzed. The Kappa-consistency testing, paired Chi-square testing and the Spearman-rank correlation testing were used to analyze the consistency between the four antimicrobial susceptibility testing methods and the gold standard.Results:Taking broth microdilution as reference, the EA of colistin broth disk elution, Vitek-2?, BD PhoenixTM, commercial broth microdilution were 94.32% (83/88), 92.05% (81/88), 90.90% (80/88), and 96.59%(85/88), respectively. The CA of all the four methods were 100% (88/88). No VME and ME were recorded for four methods. Moreover, the consistency between four susceptibility testing methods and the gold standard is acceptable (Kappa values=1, P<0.001, McNemar test P=1 and r>0.5, P<0.05). Conclusions:In the present work, four susceptibility testing methods all met the standards recommended jointly by the Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing, of which the performance of the commercial broth microdilution and CBDE fared relatively well. Thus, these four methods could be routinely used in clinical microbiology laboratory of our hospital for colistin and polymyxin B susceptibility testing.

The prevalence of colistin-resistant Gram-negative bacteria isolated from hospitalized patients with bacteremia

This study sought to investigate the prevalence of colistin-resistant Gram-negative bacteria (CoR-GNB) amongPseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae isolated frompatients with bacteremia and to identify other antimicrobials as a potential therapy for CoR-GNB infections. Weretrospectively reviewed the data of non-repeated clinical bacterial isolates from patients admitted to PhramongkutklaoHospital during May 2017–April 2018. We obtained the minimum inhibitory concentrations (MICs) of the studiedisolates and interpreted the MIC values followed by the Clinical and Laboratory Standards Institute (CLSI) criteria. Outof 623 bacterial isolates, the prevalence of E. coli was predominantly high (349), followed by K. pneumoniae (150),P. aeruginosa (64), and A. baumannii (60). The CoR-GNB rates among E. coli, K. pneumoniae, A. baumannii, andP. aeruginosa were 2.9%, 17.3%, 5.0%, and 1.6%, respectively. Seven out of 26 colistin-resistant K. pneumoniaeisolates and seven out of 10 colistin-resistant E. coli isolates were still susceptible to carbapenems (the MICs forimipenem and meropenem were ≤1 µg/ml). Tigecycline and aminoglycosides might be the best therapeutic choicesagainst CoR-GNB. In conclusion, our findings confirmed a CoR-GNB prevalence of approximately 1.6%–17.3%,depending on the bacterial species. Certain available antimicrobials remain effective against CoR-GNB.

Analysis of drug resistance pattern and genes of Salmonella.spp isolated from human infections in Anhui Province / 中华预防医学杂志

Objective@#To investigate the drug resistance pattern and drug resistance genotypes of Salmonella. spp isolated from fecal specimens and anal swabs of diarrhea cases in Anhui Province.@*Methods@#The 149 strains of Salmonella.spp isolated from feces and anal swabs of diarrhea cases in Anhui Province from April to October 2017 were selected. The serotypes of Salmonella.spp were identified by slide agglutination. The susceptibility of all strains to 14 antibiotics were determined by micro-broth dilution method. Sixty of the cephalosporin-resistant antibiotics were selected. The β-lactamase encoding genes blaTEM, blaSHV, blaOXA-1, blaOXA-2, blaPER, blaCMY, blaCTX-M, and colistin resistance genes mcr-1 and mcr-2 were performed using the multi-PCR method.@*Results@#Of the 149 diarrhea cases, the median (P25, P75) of the age was 5.0 (1.1, 38.5). The 92 of them were male and 54.4% were children. Of the 149 strains of Salmonella.spp, 105 strains had different degrees of resistance to 13 antibiotics other than imipenem. The resistance rate of ampicillin was 55.0% (82/149), which was the highest. 53.0% strains (79 strains) were multidrug resistant, main of which were Salmonella typhimurium and Salmonella enteritidis. A total of 53 resistance patterns were detected, and 10 strains were resistant to ampicillin-ampicillin/sulbactam-tetracycline-chloramphenicol-cefazolin-trimethoprim/sulfamethoxazole, which was the most common resistance pattern. Among the 60 cephalosporin resistant strains, 45 strains carried blaTEM-1, 6 of which also carried blaCTX-M-14 and 3 of which also carried blaCTX-M-65. All the 32 strains carried only blaTEM-1 show resistance to ampicillin and 31 of them show resistance to cefazolin. There were 2 strains showing negative results of gene detection. mcr-1 was detected in a multidrug resistant strain.@*Conclusion@#The resistance of Salmonella.spp to ampicillin shows a serious situation in this region, and there were a number of multidrug resistant strains. The blaTEM-1 was the major drug resistance gene detected in this research. Detection of the mcr-1 suggests the emergence of surveillance to colistin resistance of Salmonella.spp in this area.

Analysis of drug resistance pattern and genes of Salmonella.spp isolated from human infections in Anhui Province / 中华预防医学杂志

To investigate the drug resistance pattern and drug resistance genotypes of Salmonella. spp isolated from fecal specimens and anal swabs of diarrhea cases in Anhui Province. The 149 strains of Salmonella.spp isolated from feces and anal swabs of diarrhea cases in Anhui Province from April to October 2017 were selected. The serotypes of Salmonella.spp were identified by slide agglutination. The susceptibility of all strains to 14 antibiotics were determined by micro-broth dilution method. Sixty of the cephalosporin-resistant antibiotics were selected. The β-lactamase encoding genes , , (1), (2), , , , and colistin resistance genes 1 and 2 were performed using the multi-PCR method. Of the 149 diarrhea cases, the median ((25), (75)) of the age was 5.0 (1.1, 38.5). The 92 of them were male and 54.4% were children. Of the 149 strains of Salmonella.spp, 105 strains had different degrees of resistance to 13 antibiotics other than imipenem. The resistance rate of ampicillin was 55.0% (82/149), which was the highest. 53.0% strains (79 strains) were multidrug resistant, main of which were Salmonella typhimurium and Salmonella enteritidis. A total of 53 resistance patterns were detected, and 10 strains were resistant to ampicillin-ampicillin/sulbactam-tetracycline-chloramphenicol-cefazolin-trimethoprim/sulfamethoxazole, which was the most common resistance pattern. Among the 60 cephalosporin resistant strains, 45 strains carried (1), 6 of which also carried (14) and 3 of which also carried (65). All the 32 strains carried only (1) show resistance to ampicillin and 31 of them show resistance to cefazolin. There were 2 strains showing negative results of gene detection. 1 was detected in a multidrug resistant strain. The resistance of Salmonella.spp to ampicillin shows a serious situation in this region, and there were a number of multidrug resistant strains. The (1) was the major drug resistance gene detected in this research. Detection of the 1 suggests the emergence of surveillance to colistin resistance of Salmonella.spp in this area.

Non-clonal occurrence of pmrB mutations associated with polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae in Brazil

BACKGROUND Polymyxins are currently used as a "last-line" treatment for multidrug-resistant Gram-negative infections. OBJECTIVES To identify the major mechanisms of resistance to polymyxin and compare the genetic similarity between multi-drug resistant Klebsiella pneumoniae strains recovered from inpatients of public hospitals in the Mid-West of Brazil. METHODS 97 carbapenems non-susceptible K. pneumoniae were studied. β-lactamases (bla OXA-48, bla KPC, bla NDM, bla CTX-M, bla SHV, bla TEM, bla IMP, bla VIM) and mcr-1 to mcr-5 genes were investigated by polymerase chain reaction (PCR). Mutations in chromosomal genes (pmrA, pmrB, phoP, phoQ, and mgrB) were screened by PCR and DNA sequencing. Clonal relatedness was established by using pulsed-field gel electrophoresis and multilocus sequence typing. FINDINGS K. pneumoniae isolates harbored bla KPC (93.3%), bla SHV (86.6%), bla TEM (80.0%), bla CTX-M (60%) genes. Of 15 K. pneumoniae resistant to polymyxin B the authors identified deleterious mutations in pmrB gene, mainly in T157P. None K. pneumoniae presented mcr gene variants. Genetic polymorphism analyses revealed 12 different pulsotypes. MAIN CONCLUSIONS Deleterious mutations in pmrB gene is the main chromosomal target for induction of polymyxin resistance in carbapenem-resistant K. pneumoniae in public hospitals in the Mid-West of Brazil.

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

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

Research advance in Enterobacteria ceaebacteria resistant to polymyxins / 中华检验医学杂志

In order to deal with the increasing number of multidrug resistant Enterobacteriaceae , polymyxins were re-introduced into clinical practice .The resistance of polymyxins had gained global attention.In addition to chromosomal mediated drug resistance , a new plasmid-mediated colistin-resistance gene mcr-1 made transferation of polymyxins resistance more easily .Here, the mechanisms of chromosome mediated polymyxin resistance and plasmide-mediated drug resistance , including the distribution , prevalence, transfer mechanism, and genetic environments of mcr-1, current methods for polymyxins susceptibility testing methods and novel qualitative detection techniques were reviewed to provide information to cope with the growing problem of bacterial drug resistance .

Lesão renal aguda associada ao uso de polimixinas em pacientes críticos / Acute kidney injury associated with the use of polymyxins in critically ill patients

Introdução: A Lesão renal aguda (LRA) é uma síndrome de alta incidência (23,2%) e mortalidade (23,0%), que acomete principalmente pacientes críticos, internados em unidades de terapia intensiva (UTI). A sepse é a principal causa de LRA (40,0%). A infecção por microrganismos multirresistentes exige o uso de agentes antimicrobianos potencialmente nefrotóxicos, como as polimixinas (Pmxs). Dentre elas, destaca-se a Pmx B e a colistina (Pmx E) utilizadas no controle de infecções por bacilos gram negativos (BGN). Objetivos: avaliar a incidência de LRA associada ao uso de Pmxs e identificar os fatores de risco para desenvolvimento de LRA associada ao uso de Pmxs. Métodos: Trata-se de um estudo transversal, retrospectivo, de abordagem quantitativa. A amostra foi composta por 1009 pacientes internados em UTI, provenientes de um banco de dados universal (BDU) organizado no período de abril a dezembro de 2012. Resultados: Foram incluídos 936 pacientes. A incidência geral de LRA na amostra foi de 43,1%, enquanto que para pacientes que receberam Pmxs foi de 87,0%. O principal fator de risco para LRA geral foi a pré existência de Doença Renal Crônica. Dentre os pacientes com LRA e que fizeram uso de Pmxs, a maioria era do sexo masculino (69,2%); 54,4±15,7 anos, internação do tipo clínica e com o maior tempo de internação em UTI, as características clínicas mais prevalentes foram o estado de choque (81,5%), a hipertensão arterial sistêmica (35,3%), o Diabetes Mellitus (20,0%) e a sepse (23,0%). Esse grupo apresentou maiores índices de gravidade SAPS II e LODS e o choque se confirmou como fator de risco nesse grupo. Conclusões: As Pmxs confirmaram-se como medicamento nefrotóxico em pacientes críticos (87%), tendo o choque como fator de risco.

Introduction: Acute kidney injury (AKI) is a syndrome of high incidence (23.2%) and mortality (23.0%), which affects mainly critically ill patients admitted to intensive care units (ICUs). Sepsis is the main cause of AKI (40.0%). Infection with multiresistant microorganisms requires the use of potentially nephrotoxic antimicrobial agents, such as polymyxins (Pmxs). Among them, Pmx B and colistin (Pmx E) are used to control gram-negative bacilli (GNB) infections. Objectives: to evaluate the incidence of AKI associated with the use of Pmxs and to identify the risk factors for the development of AKI associated with the use of Pmxs. Methods: It´s a cross-sectional, retrospective, quantitative approach The sample consisted of 1009 patients hospitalized in ICUs from a universal database (BDU) organized from April to December 2012. Results: A total of 936 patients were included. The overall incidence of AKI in the sample was 43.1%, whereas for patients receiving Pmxs it was 87.0%. The main risk factor for overall AKI was the pre-existence of Chronic Kidney Disease. Among the patients with AKI who used Pmxs, the majority were male (69.2%); 54.4 ± 15.7 years, hospitalization of the clinical type and with the longer ICU stay. The most prevalent clinical characteristics in the AKI and Pmx groups were shock state (81.5%), systemic arterial hypertension (35.3%), Diabetes Mellitus (20.0%) and sepsis (23.0% ). This group presented highest SAPS II and LODS severity indexes and the shock was confirmed as a risk factor. Conclusions: Pmxs were confirmed as nephrotoxic drugs in critical patients (87%), with shock as a risk factor.

Caracterização clínica, microbiológica e molecular e tratamento de infecções por enterobactérias resistentes aos carbapenêmicos / Clinical, microbiology and molecular characterization and treatment of infections with carbapenem-resistant Enterobacteriaceae

Introdução: Infecções por Enterobactérias resistentes aos carbapenêmicos (ERC), em especial produtoras de Klebsiella pneumoniae carbapenamase tipo KPC hoje são endêmicas em diversas regiões do mundo, seu tratamento é ainda um grande desafio em particular de isolados resistentes à polimixina. Objetivos: Descrever as características clínicas, microbiológicas e moleculares das infecções por ERC. Método: Estudo de coorte prospectiva, realizado no Hospital Universitário de Londrina, Paraná, Brasil, entre março de 2011 a dezembro de 2012. Foram acompanhados pacientes >= 18 anos, que apresentaram infecção por ERC. Dados demográficos e clínicos como idade, sexo, diagnóstico à admissão e presença de co-morbidades de acordo com critérios de Charlson, internação em Unidade de Terapia intensiva e scores APACHE e SOFA desses pacientes, colonização prévia por ERC, cirurgia prévia à infecção, diálise, uso prévio de antimicrobianos e sítio de infecção foram coletados. Foram avaliados os antimicrobianos utilizados para tratamento das infecções por mais de 48 horas nos seguintes pontos: monoterapia ou terapia associada, tempo de início (menor e maior que 12 horas). A identificação do agente foi realizada por método automatizado (Vitek II - bioMerieuxR) e a concentração inibitória mínima dos antibióticos por técnica de microdiluição em caldo, pesquisa de gene blaKPC pela técnica de Polimerase Chain Reaction e sinergismo entre drogas utilizadas em tratamento combinado por meio do método Time Kill. A clonalidade, por Pulsed Field gel eletroforese e analisada por dendograma pelo Bionumerics. Foram realizadas análise bivariada e regressão logística multivariada com técnica de Forward Stepwise para detectar fatores de risco para resistência a polimixina e mortalidade. O nível de significância adotado foi de 5%, utilizando os programas Epi Info 7.0 e SPSS. Resultados: No período de estudo, 127 pacientes apresentaram infecções por ERC, idade média de 55,7 (± 18) anos e 88 (69.3%) do...

Introduction: Infections due to Carbapenem resistant Enterobacteriaceae (CRE), particularly Klebsiella pneumoniae producing carbapenemase type KPC, have been endemic in several regions around the world. Their treatment remains a major challenge, particularly for isolates resistant to polymyxin. Objectives: To describe the clinical, microbiological and molecular characteristics of infections by CRE. Methods: Prospective cohort conducted at the University Hospital of Londrina, Paraná, Brazil, from March 2011 to December 2012. All hospitalized patients >= 18 years old who developed infection by CRE were followed until death or discharge. We collected and analyzed the following clinical data: age, sex, diagnosis at admission, presence of comorbidities according to the Charlson criteria, admission in Intensive Care Unit, APACHE and SOFA scores, previous colonization by CRE, previous surgery, dialysis, prior antibiotic use and infection site; furthermore, we also evaluated the time between the blood culture collect and the first antimicrobial dose administration (start time - smaller or longer than 12 hours) as well as whether the treatment was monotherapy or combine therapy for more than 48 hours. The microbiological identification was performed by automated method (Vitek II - bioMerieuxR) and the minimum inhibitory concentration of antibiotics by broth microdilution technique, research blaKPC gene by the technique of Polymerase Chain Reaction and synergism between the drugs used in the combination therapy by Time Kill method. The clonality was carried out by pulsed-field gel electrophoresis and analyzed by dendrogram by BioNumerics. Bivariate analyses and multivariate logistic regression with forward stepwise technique were performed to detect risk factors for resistance to polymyxin and mortality. The level of significance was 5%, using Epi Info 7.0 and SPSS programs. Results: During the study period, 127 patients developed infections by CRE,...

Therapy of Infections due to Carbapenem-Resistant Gram-Negative Pathogens / 감염과화학요법

The prevalence of carbapenem-resistant gram-negative bacterial pathogens (CRGNs) has increased dramatically during the last 10 years, but the optimal treatment for CRGN infections is not well established due to the relative scarcity of robust clinical data. The polymyxins remain the most consistently active agents against CRGNs in vitro. Tigecycline, based on its in vitro antibacterial spectrum, could also be considered as a therapeutic option in the treatment of infections caused by certain CRGNs. Other agents, including aminoglycosides, rifampin, trimethoprim-sulfamethoxazole, fosfomycin and fluoroquinolones, could be considered as monotherapy or combination therapy against CRGNs in appropriate contexts, as combination therapy with two or more in vitro active drugs appears to be more effective than monotherapy based on some clinical data. Several promising new agents are in late-stage clinical development, including ceftolozane-tazobactam, ceftazidime-avibactam and plazomicin. Given the shortage of adequate treatment options, containment of CRGNs should be pursued through implementation of adequate infection prevention procedures and antimicrobial stewardship to reduce the disease burden and prevent future outbreaks of CRGNs.

Eficacia, tolerancia y seguridad de una combinación de metronidazol, miconazol, centella asiática, polimixina y neomicina en cápsula blanda para uso vaginal en el tratamiento de la vaginosis bacteriana / Efficacy, tolerability, and safety of a combination including metronidazole, miconazole, Gotu kola, polymixin, and neomycin in soft vaginal capsules for the treatment of bacterial vaginosis

Introducción: La vaginosis bacteriana (VB) es un síndrome polimicrobiano, en la cual la flora dominante de lactobacilos normales es sustituida por una flora polimicrobiana. La prevalencia de VB en Perú varía entre 27 y 43,7%. El Centro de Control y Prevención de Enfermedades (DCD) sugiere el tratamiento de VB en mujeres sintomáticas con metronidazol oral/gel o clindamicina crema. Se planteó en el presente estudio evaluar la eficacia, tolerancia y seguridad de la combinación de metronidazol, miconazol, centella asiática, polimixina y neomicina en cápsula blanda para el tratamiento de VB. Material y Métodos: El presente estudio de tipo abierto, observacional, prospectivo, permitió evaluar la eficacia, tolerancia y seguridad en la aplicación de la combinación de metronidazol, miconazol, centella asiática, polimixina y neomicina en cápsula blanda. Resultados: Se incluyó a 61 pacientes con edad promedio de 29.28 años (rango 18-48) de las cuales 93,4% tenía historia previa de flujo vaginal anormal. Se realizaron dos visitas durante el estudio, la primera para diagnóstico e inicio de tratamiento y la segunda de control post tratamiento. Tres pacientes no tuvieron segunda visita y 8 no tenían registrada toda la información para definir la respuesta terapéutica. La segunda visita se realizó a los 21 días en promedio. Los principales signos y síntomas en la primera visita de diagnóstico fueron flujo vaginal (100,0%), disconfort vaginal (85,2%), dispareunia (70,5%) y dolor abdominal bajo (57,4%), las cuales disminuyeron en forma significativa (p<0,05) a la segunda visita post tratamiento. La prueba de aminas resultó positiva en el 93,4% de los casos en la primera visita y en el 15,5% de los casos en la segunda visita (p<0,05). De la población inicial de estudio, solo 53 mujeres son evaluables para eficacia terapéutica...

Introduction: Bacterial vaginosis (BV) is a polymicrobial syndrome, in which the normal dominant flora consisting in Lactobacillus is replaced by polymicrobial flora. The prevalence of BV in Peru varies between 27 and 43.7%. The Centers for Disease Control and Prevention suggest therapy for BV in symptomatic women should include oral/gel metronidazole or clindamycin cream. We proposed in this study to evaluate the efficacy, tolerability and safety of the combination of metronidazole, miconazole, Gotu kola (Centella asiatica), polymixin, and neomycin in soft capsules, for the treatment of BV. Material and Methods: This investigation was an open, observational, and prospective study, which allowed us to evaluate the efficacy, tolerability and safety of the aforementioned combined therapy administered in soft capsules. Results: The study included 61 patients with a mean age of 29.28 years (range, 18-48) and 93.4% had a history of abnormal vaginal discharge. Two visits took place during the study, the first for making the diagnosis and initiating therapy, and the second was the post-treatment control. Three patients did not have a second visit and 8 did not record all the information required to define the therapeutic response. The second visit took place after 21 days on average. The main signs and symptoms at the first visit were vaginal discharge at diagnosis (100.0%), vaginal discomfort (85.2%), dyspareunia (70.5%) and lower abdominal pain (57.4%), which were significantly reduced (p <0.05) in the second visit after treatment. The amine test was positive in 93.4% of cases in the first visit and in 15.5% of cases in the second visit (p <0.05). From the initial population in the study, only 53 women are evaluable for efficacy. An overall response rate in 44 women (83.02%) was achieved with the soft capsule combination treatment. Adverse events were reported in only one case...

Antimicrobial Resistance and Clones of Acinetobacter Species and Pseudomonas aeruginosa

Antimicrobial resistance in bacteria is problematic in clinical settings and is a growing threat to public health. Multidrug-resistant and pandrug-resistant non-fermenters such as Acinetobacter spp. and Pseudomonas aeruginosa have recently emerged as a great concern worldwide. Particularly, the prevalence of carbapenem resistance in Acinetobacter spp. and P. aeruginosa is problematic, and emergence of polymyxin resistance is ominous. In this review, we discuss carbapenem and polymyxin resistance in Acinetobacter spp. and P. aeruginosa isolates and their major clones.

The role of free amino groups of peptides and proteins in the Folin-Lowry and biuret methods.

On an equal weight basis polymyxin Β and EM 49 which do not contain tyrosine or tryptophan yielded the same colour intensity as proteins in the Folin-Lowry and biuret methods. But, in the absence of reagent C (alkaline copper reagent) polymyxin Β and EM 49 yielded no colour in the Folin-Lowry method. Mono-, di- and tri-formyl polymyxins Β formed identical amounts of coloured complexes as polymyxin Β in the two methods. However, the tetra- and penta-formyl polymyxins Β yielded only one-fifth and one-sixth, respectively, of the expected colour in the Folin-Lowry method. Similarly, 40% and 30%, respectively, of the anticipated amount of colour is formed in the biuret method. Formylated and methylated lysozyme and bovine serum albumins form only 70-75% of the expected colour in the Folin-Lowry method. Since formation of colour by reduction of Folin reagent, in the Folin-Lowry method, is at least partly due to complexes of copper, it was inferred that polymyxin Β as well as its mono-, di- and tri-formyl derivatives on the one hand and the tetra- and penta-formyl derivatives on the other differ in their ability to complex Cu(II) The former group of compounds was indeed found to complex as many as three Cu(II) ions whereas the tetra- and penta-formyl polymyxins Β complexed only one equivalent, under conditions of excess Cu(II). Under conditions of low Cu(II), polymyxin Β and all its derivatives complexed only one Cu(II). In proteins, sites other than amino groups which complex Cu(II) probably play a major role in the reduction of the Folin reagent, since methylated lysozyme and bovine serum albumin yield 70-75% of the colour formed by the unmodified proteins in the Folin-Lowry reaction.