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Introduction. Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is difficult to control, has high morbidity and mortality, and demands priority public health intervention. In Colombia, MDR/RR-TB has been becoming more widespread annually. Before the COVID-19 pandemic, over an 8-year period, the number of cases of multidrug-resistant tuberculosis in Colombia was close to a thousand cases. Timely identification of the different risk factors for MDR/RR-TB will contribute fundamentally to the systematic management. Objective. To determine which risk factors were associated with the presentation of MDR in Colombia between 2013 and 2018. Materials and methods. A retrospective case-control study was carried out, for which the data from the routine surveillance of MDR/events in the country were used. Results. The cases of multidrug-resistant tuberculosis were mainly in young people, Afrodescendants, and males. Of the clinical conditions, comorbidities such as malnutrition, diabetes, and HIV, presence of at least one factor, such as drug dependence, taking immunosuppressive medications, belonging to the black race, afro, and living in an area of high disease burden were risk factors. Conclusion. In addition to the diagnosis and timely provision of MDR-TB treatment, it is necessary that public health programs at the local level pay special attention to patients with the identified risk factors.

Objectives. To determine the proportion of Salmonella enterica in fecal samples of live pigs with suspected salmonellosis analyzed at the diagnostic unit of the University of Antioquia, Colombia between 2019 and 2021, and examine the serotypes and antimicrobial resistance patterns. Methods. This was a laboratory-based cross-sectional study of routine data on fecal samples received from pig farms in all nine subregions of Antioquia state, Colombia. Salmonella spp. detection at the university is done using enrichment, selective culture, and polymerase chain reaction. Serotypes were identified using the Kauffmann–White scheme and isolates were tested for antimicrobial susceptibility using broth microdilution. Results. Of 653 samples tested, 149 (23%) were positive for S. enterica. Nine serotypes were identified. The most common were Salmonella Typhimurium (56%) and its monophasic variant (35%). Resistance to ampicillin (70%) was most frequently observed, followed by ciprofloxacin (55%), and sulfamethoxazole–trimethoprim (52%). No isolates were resistant to amikacin and gentamicin. Multidrug resistance (resistance to ≥ 3 classes of antibiotics) was observed in 61 (44%) isolates. Multidrug resistance was highest in S. Typhimurium (57%) compared with the other serotypes. Serotype was associated with multidrug resistance (p = 0.01), but age of the pig and sub-region were not. Conclusions. The proportion of Salmonella spp. and the associated high levels of multidrug resistance are of concern and may indicate irrational use of antimicrobials and poor management practices in pig production systems in the region. Strengthened surveillance is needed to monitor and improve farm management practices and the use of antimicrobials in farms in Colombia.

Objective. To describe the resistance profile and the genetic characteristics of Escherichia coli isolates that harbor the mobilizable colistin resistance gene mcr-1 in Argentina. Methods. This was a retrospective study of 192 E. coli isolates positive for mcr-1 obtained from 69 hospitals of Buenos Aires City and 14 Argentinean provinces in 2012 – 2018. The antimicrobial susceptibility was performed by agar diffusion, broth macrodilution, and/or agar dilution. Standard polymerase chain reaction (PCR) was performed to detect resistance genes and incompatibility groups; specific PCR was applied to discriminate between blaCTX-M allelic groups and mcr-1.5 variant. The genetic relatedness among isolates was evaluated by XbaI-pulsed field gel electrophoresis and multilocus sequence typing in a subset of isolates. Results. All E. coli isolates showed minimal inhibitory concentrations to colistin ≥ 4μg/mL; nearly 50% were resistant to third-generation cephalosporins, with CTX-M-2 being the main extended-spectrum β-lactamase detected. Five E. coli were carbapenemase-producers (3 NDM, 2 KPC). The mcr-1.5 variant was detected in 13.5% of the isolates. No genetic relationship was observed among the mcr-1-positive E. coli clinical isolates, but a high proportion (164/192; 85.4%) of IncI2 plasmids was detected. Conclusions. The presence of IncI2 plasmids among highly diverse E. coli clones suggests that the mcr-1 gene’s wide distribution in Argentina may be driven by the horizontal transmission of IncI2 plasmids.

Acinetobacter baumannii is considered to be a worldwide threat to public health due to its high antimicrobial resistance rates and the severe infections it can cause. Little is known about this pathogen’s resistance in Central America. This report aims to describe the antimicrobial resistance profile of A. baumannii at a tertiary hospital in Honduras. The cross-sectional analysis was conducted at the tertiary care laboratory hospital in San Pedro Sula in 2015 – 2017. A total of 113 consecutive microbiological reports were analyzed, comprising 100 individuals from whom A. baumannii was isolated. Epidemiological and microbiological data, including the isolation setting and patient information, were recorded. Prevalence of multi-drug and extensive-drug resistance was assessed according to international standards. The median age of individuals was 22 years (2 – 35 years); female was the predominant gender (53%). The hospital’s pediatric wards had the highest number of isolates (n = 48). The most frequent specimen from which A. baumannii was isolated was skin and soft tissue (n = 39). Resistance to carbapenems was reported to be 40.7% among the isolates (n = 46); multi-drug resistant, 35.4% (n = 40); and extensively-drug resistant, 7.1% (n = 8). This report reveals the threat of this pathogen to public health in Honduras and appeals for antibiotic stewardship programs throughout Central America.

Introduction: The use of antibiotics in humans, animal husbandry and veterinary activities induces selective pressure leading to the colonization and infection by resistant strains. Objective: We evaluated water samples collected from rivers of the Guanabara Bay, which have suffered minor and major environmental degradation, and clinical samples of hospital origin to detect evidence of the presence of resistance genes to aminoglycosides, beta-lactam antibiotics and fluoroquinolones in strains of Klebsiella pneumoniae subsp. pneumoniae, K. pneumoniae subsp. ozaenae and Escherichia coli. Materials and methods: For isolation of the water strains we employed culture media containing 32 μg/ml cephalotin and 8 μg/ml gentamicin. The strains from clinical materials were selected using culture media containing 8 μg/ml gentamicin. The strains were identified and subjected to antimicrobial susceptibility testing (AST), plasmid DNA extraction and polymerase chain reaction (PCR) to detect genes encoding enzymes modifying aminoglycosides (EMA), extended-spectrum beta-lactamases (ESBL) and plasmid mechanisms of quinolone resistance (PMQR). Results: The AST of the isolates recovered from water samples showed multidrugresistance profiles similar to those found in isolates recovered from clinical materials. All isolates from water samples and 90% of the isolates from clinical samples showed at least one plasmid band. In the PCR assays, 7.4% of the isolates recovered from water samples and 20% of those from clinical materials showed amplification products for the three antimicrobial classes. Conclusion: We believe that the detection of microorganisms presenting genetic elements in environments such as water is necessary for the prevention and control of their dissemination with potential to infect humans and other animals in eventual contact with these environments.

O progresso na compreensão dos mecanismos de resistência aos fármacos usados no tratamento da tuberculose tem permitido o desenvolvimento de novos métodos para a detecção da tuberculose resistente. A resistente aos fármacos representa uma ameaça para os programas de controle da tuberculose. Para tanto, é necessário conhecer o padrão de sensibilidade das linhagens para fornecer o tratamento adequado. Os estudos moleculares dos mecanismos de ação dos fármacos antituberculose têm elucidado as bases genéticas da resistência aos fármacos em Mycobacterium tuberculosis. Os mecanismos de resistência aos fármacos na tuberculose são causados por mutações cromossomais em diferentes genes da bactéria. Durante a exposição aos fármacos, há uma pressão seletiva favorecendo o desenvolvimento de linhagens resistentes. A tuberculose multirresistente é um problema nacional e internacional que traz sérias dificuldades para o controle global da doença. Realizou-se uma revisão sobre os mecanismos moleculares associados à resistência aos fármacos com ênfase nas novas perspectivas para detectar os isolados resistentes.Progress to understanding the basis of resistance to antituberculous drugs has allowed molecular tests for detection of drug-resistant tuberculosis to be developed. Drug-resistant tuberculosis poses a threat to tuberculosis control programs. It is necessary thus to know drug susceptibilities of individual patient's strain to provide the appropriate drug combinations. Molecular studies on the mechanism of action of antituberculous drugs have elucidated the genetic basis of drug resistance in M. tuberculosis. The mechanisms of drug resistance in tuberculosis are a result of chromosomal mutations in different genes of the bacteria. Upon drug exposure there is a selective pressure for such resistant mutants. Multidrug-resistant tuberculosis is a health problem of increasing significance for the whole global community. This paper reviews the molecular mechanisms associated with drug-resistance as well the new perspectives for detecting resistant isolates.

The approach to public health, patient safety and quality of care has led to analysing health situations or problems from a population perspective, in a wide way and giving priority to factors that can normally be left in the background from a clinical point of view. For years, the problem of the use and abuse of antimicrobials, the increase and diffusion of microorganisms resistant to them, cross-transmission, and healthcare related infections have been prioritised both nationally and internationally. To combat these problems, various strategies are being developed and put into practice, from the policies of rational use and optimization of antimicrobials, surveillance, and control of infections related to health care, to training information and awareness strategies. One of the pillars of surveillance and control is the correct application of standard and specific precautions, which within the framework of these comprehensive programs aim to control the transmission of microorganisms of special microbiological and/or epidemiological interest through a series of measures. In hospitals, the application of these precautions (single room, barrier measures, restrictions on access to rooms, waste management…) in patients infected or colonised by these microorganisms can have different repercussions, both for patients and the professionals that attend them, and it is considered pertinent that the protocols and/or programs of specific precautions explicitly include the analysis of the ethical aspects in their preparation, implementation, and monitoring., (Copyright © 2020 FECA. Publicado por Elsevier España, S.L.U. All rights reserved.)

O progresso na compreensão dos mecanismos de resistência aos fármacos usados no tratamento da tuberculose tem permitido o desenvolvimento de novos métodos para a detecção da tuberculose resistente. A resistente aos fármacos representa uma ameaça para os programas de controle da tuberculose. Para tanto, é necessário conhecer o padrão de sensibilidade das linhagens para fornecer o tratamento adequado. Os estudos moleculares dos mecanismos de ação dos fármacos antituberculose têm elucidado as bases genéticas da resistência aos fármacos em Mycobacterium tuberculosis. Os mecanismos de resistência aos fármacos na tuberculose são causados por mutações cromossomais em diferentes genes da bactéria. Durante a exposição aos fármacos, há uma pressão seletiva favorecendo o desenvolvimento de linhagens resistentes. A tuberculose multirresistente é um problema nacional e internacional que traz sérias dificuldades para o controle global da doença. Realizou-se uma revisão sobre os mecanismos moleculares associados à resistência aos fármacos com ênfase nas novas perspectivas para detectar os isolados resistentes.

Objetivos. Determinar los perfiles de resistencia de las quinolonas; ciprofloxacina (Cpx), ofloxacina (Ofx), gatifloxacina (Gfx) y moxifloxacina (Mfx), y de los inyectables; kanamicina (Km), amikacina (Am) y capreomicina (Cm) en cepas multidrogorresistente (MDR). Se buscó la presencia de mutaciones en los genes rrs,tlyA y gyrA/B, y su posible asociación con la resistencia a inyectables y quinolonas. Materiales y métodos. En este estudio piloto descriptivo se seleccionaron cepas MDR aisladas durante junio a diciembre de 2004, que fueron criopreservadas en el banco de muestras del Instituto de Medicina Tropical "Alexander von Humboldt" en Lima, Perú. Se determinó la concentración mínima inhibitoria (CMI) para Cpx, Ofx, Gfx, Mfx, Km, Am y Cm. Se investigó las mutaciones presentes en los genes rrs, tlyA y gyrA/B a través de un PCR convencional y posterior secuenciamiento de los productos obtenidos. Resultados. Cuatro de los once aislados presentaron resistencia contra los inyectables y en todas se observó una alta CMI; >120 μg/mL para Km y >160 μg/mL para Am y Cm. Solo dos aislados presentaron resistencia a Ofx con un CMI = 4 μg/mL. Los resultados de secuenciamiento sugirieron que la mutación A1401T en rrs podría ser la causa molecular de resistencia a los inyectables; mientras que en este estudio no se halló ninguna mutación en tlyA ni en gyrA/B asociada a resistencia. Conclusiones. Este estudio sugiere una posible asociación entre la mutación en A1401G y la resistencia a los antibióticos inyectables.

Microorganisms that cause diseases in humans are constantly evolving, which represents a challenge in the search for effective treatments against them. Even when currently there are several pharmacological alternatives available, sometimes they are inefficient for the control of infectious diseases, especially because pathogens have generated multiple resistance mechanisms against them. Antimicrobial peptides have been described in many species of organisms, from fungi, plants and insects to humans; currently, there are molecules that appear as a solution that can be effective in modern therapeutics. The advantage of these natural peptides lies in that they have been evolving almost the same amount of time than the species that produce them and their effect on the control of microorganisms is highly significant; some of these molecules are isolated from living organisms, others are starting to be produced by synthetic methods, which allows having access to an endless number of peptides with diverse therapeutic activities., (Copyright: © 2018 SecretarÍa de Salud.)

Background: P-gp and BCRP1 are transporter proteins that may confer drug resistance., Objective: To compare P-gp and BCRP1 function in rheumatoid arthritis patients with active and inactive disease and to define their relation with disease activity., Methods: We included 17 active patients paired (age, gender, disease duration) to 17 inactive patients. All had baseline evaluations and 27 had additional six-month follow-up. P-gp and BCRP1 functional activity was measured in peripheral mononuclear cells by flow cytometry. Percentage of lymphocytes able to extrude substrates for P-gp and BCRP1 were recorded in the presence/absence of selective inhibitors. Informed consent was obtained. Descriptive statistics and linear regression model were applied., Results: Active patients had higher efflux function of both transporters than inactive patients: median (25-75 IQR) P-gp of 7.1% (1.4-29.3) vs. 1.6% (0.7-3.5), p = 0.02 and BCRP1 of 6.2% (1.3-22.4) vs. 1.3% (0.7-2), p = 0.007. At baseline, disease activity was the only predictor of both transporter functions. At follow-up, changes in disease activity correlated with shift in P-gp (r = 0.35, p = 0.07) and BCRP1 (r = 0.33, p=0.09) function., Conclusions: Patients with active rheumatoid arthritis had a higher efflux function of P-gp and BCRP1 compared to inactive patients. The behavior of P-gp and BCRP1 appeared to be conditioned by disease activity.

The long-term care facilities (LTCF) are the health care level that integrates medical assistance and social services according to the requirements of its beneficiaries. There is a great variability depending on the users profile, the professional staff and accessibility to technical resources for diagnosis, treatment or rehabilitation. In LTCF different factors are shaping a challenge in the infection control. These factors are high prevalence of infection and colonization by multiresistant microorganisms (MROs), a high rate of, often inadequate, antibiotic prescriptions, the high transfer of hospital patients, and the lack of diagnostic resources. In infection studies in LTCF, one of the main problems is the lack of standard, and well defined, infection criteria. The special features of infections in the elderly population, together with the limited resources, make it necessary to establish standard and worldwide validated criteria in order achieve appropriate monitoring and control of infection. The most common infection is the respiratory, followed by the urinary, skin and soft tissue, gastro-intestinal tract, and eyes. The problematic microorganisms most frequently identified in LTCF are enterobacteriaceae extended spectrum beta lactamase, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). A successful infection control mainly depends on two actions. First, a high compliance of standard precautions and second, patient organization according to the risk of transmission of a particular MROs infection, especially MRSA. This risk classification may be a way to rationalize application measures, and the incorporation of ethical and legal issues. The level of stratification is established mainly according to the condition of being colonized or infected, the MROs anatomical location, and the degree of behavioral disorders suffered by the patient. Implementation of extensive screening programs or complex monitoring programs, as in acute care hospitals are not indicated. The epidemiological surveillance must adapt to clinical guidelines, with the registering of colonized and infected patients being mandatory, along with the coordination between health and social systems by applying global control programs., (Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Objective: To evaluate the effectiveness of an educational program for the prevention of healthcare-associated infections (HCAIs), based on Care Bundles., Material and Methods: A quasi-experimental study conducted in a university hospital from May 2011 to February 2012. An educational intervention (21 training sessions) was carried out in all Departments with the support of the contents in a leaflet, which included evidence-based Care Bundles for prevention of different HCAIs. The leaflet was also distributed through all Hospital Departments. We assessed the knowledge of health care workers (HCWs) as regards preventive measures before and after each training session using a self-administered questionnaire, and we studied the frequency of patients with HCAIs before and after the intervention., Results: One-hundred-and-sixty-five out of 398 HCWs (41.5%) attended the training sessions. Their knowledge improved significantly, mainly in terms of: a) antimicrobial activity of alcohol-based solutions, b) preventive measures for cathether-associated urinary tract infections, and c) best place to insert a central venous catheter. These areas increased after training by 53.1, 29.7, and 28.2 points, respectively. There was a non-significant decrease in the incidence of patients with HCAIs by multiresistant microorganisms, and a non-significant increase in the prevalence of patients with HCAIs., Conclusions: The educational program improved the knowledge of the HCWs about preventive measures for HCAIs, whereas the prevalence of patients with HCAIs did not show significant changes in the period of study., (Copyright © 2012 SECA. Published by Elsevier Espana. All rights reserved.)

Introduction: Physiological resistance of natural population of Aedes aegypti to insecticides contribute to the decreased efficacy of chemical control as a main control strategy during dengue outbreaks., Objective: The susceptibility status of Ae. aegypti was assessed for the carbamate propoxur, the adulticide malathion and the larvicide temephos on 13 natural populations of Ae. aegypti immature forms were taken from 8 Colombian localities. These included the following: Bucaramanga (1), Sabana de Torres (2), Girardot (2), La Mesa (2), Villavicencio (2), Puerto López (2), San José del Guaviare (1) and Florencia (1)., Materials and Methods: Susceptibility tests mainly consisted of the standardized bioassay outlined by WHO (1981) and CDC bottles (1998). Colorimetric tests were undertaken to determine enzyme levels possibly responsible for the reduction of susceptibility to organophosphate and carbamate insecticides., Results: All specimens demonstrated susceptibility to malathion and propoxur insecticides. Four of the 13 populations revealed susceptibility to the temephos larvicide. Seven of 11 populations showed a limited increase in values for nonspecific esterase enzymes. The Bucaramanga population was the only one which showed an increase in the cytochrome P450 monooxygenases enzymes. Neither population was found with modified acetilcolinesterase., Conclusions: The widespread susceptibility to organophosphates used as adulticides indicated that malathion, the most used insecticide in Colombia, remains effective in interrupting the transmission of dengue. Physiological resistance to insecticides occurring in communities of a single township proved to be a localized phenomenon.

Introduction: The susceptibility of Anopheles albimanus to organophosphates, carbamates and pyrethroid insecticides was unknown in the Panama communities of Aguas Claras, Pintupo and Puente Bayano, located in the Amerindian Reservation of Madungandi. This region is considered a malaria transmission area, where An. albimanus is the main vector., Objective: The resistance to organophosphate insecticides, carbamates and pyrethroids was evaluated in field populations of the Anopheles albimanus in Panama., Materials and Methods: Progeny of An. albimanus collected in three localities in the indigenous Madugandi region were exposed to bioassays of susceptibility to organophosphate insecticides (fenitrothion, malathion and chlorpyrifos), the carbamate (propoxur) and pyrethroids (deltamethrin, lambdacyhalothrin, cyfluthrin and cypermethrin). The protocols were in accordance with those established for adult mosquitoes by World Health Organization., Results: The three strains of the An. albimanus were resistant to the pyrethroid insecticides deltamethrin, lambdacyhalothrin, cyfluthrin and cypermethrin. Susceptibility remained for the organophosphate insecticides fenitrothion, malathion, chlorpyrifos, and the carbamate insecticide propoxur., Conclusion: The results provided important information to the vector control program, contributing to the application of new strategies on the use of insecticides, and thereby lengthening the life of the insecticide in use.

Objectives: To assess the susceptibility status of 13 natural populations of Aedes aegypti (collected from sites in Colombia where dengue is a serious public health problem) to the pyrethroids, deltamethrin and lambda-cyhalothrin, and to the organochlorine, DDT, and to identify any biochemical mechanisms associated with resistance., Methods: Immature forms of the vector were collected from natural breeding spots at each site and then raised under controlled conditions. Using the F2 generation, bioassays were performed using the World Health Organization's 1981 methodology (impregnated paper) and United States Centers for Disease Control and Prevention's 1998 methodology (impregnated bottles). In populations where mortality rates were consistent with decreased susceptibility, levels of nonspecific esterases (NSE), mixed-function oxidases (MFO), and acetylcholinesterase (AChE) were measured using colorimetric tests., Results: All of the mosquito populations that were tested showed resistance to the organochlorine DDT. In the case of the pyrethroids, widespread resistance to lambda-cyhalothrin was found, but not to deltamethrin. Assessing the biochemical resistance mechanisms showed that 7 of the 11 populations had elevated NSE, and one population, increased MFO., Conclusions: Physiological cross-resistance between DDT and lambda-cyhalothrin in the A. aegypti populations tested was dismissed. Physiological resistance to lambda-cyhalothrin appears to be associated with increased NSE. The differences in susceptibility levels and enzyme values among the populations were associated with genetic variations and chemicals in use locally.

Introduction: This study has been designed to know the use of these antibiotics (ATB) in Intensive Care Units (ICUs)., Design and Patients: A multicentric, prospective, observational study was conducted. In cluded as cases were the indications of vancomycin (VAN), teicoplanin (TPN), quinupristin/dalfopristin (Q/D) and linezolid (LZD)., Results: A total of 826 indications (VAN 52.1%, TPN 36.6%, LZD 11.6% and Q/D 0%) were analyzed, 793 (96%) as treatment and 33 (4%) as prophylaxis in 818 patients. Serious sepsis or septic should occurred in 55.9% of the patients treated. The most common infections were pneumonia and catheter-related bacteremia, 48.3% of all the infections being acquired in ICUs. LZD was used mostly in mechanical-ventilation related pneumonia (p = 0.001), VAN in community Central Nervous System infections (p = 0.01) and in catheter-related bacteremia (p = 0.001), TPN in community pneumonia (p = 0.01) and in catheter-related bacteremia (p = 0.001). Treatments were empirical in 65.8% and diagnosis of gram positive cocci was confirmed in 48.3% of them. Staphylococcus aureus was isolated more in the LZD-treated group. Initial treatment was modified 224 times, this occurring more frequently in the VAN-treated group. The reason for this change was clinical failure 59 times, this being more frequent in the TPN group and less frequent in the patients treated with LZD, which was the drug used the most in rescue therapies (43/69, 62.3%). Adverse events, probably related to the ATB, were identified in 36/826 (4.4%) cases., Conclusions: The most common use of this ATB was to treat ICU-acquired infections. VAN was the most frequently used drug. Treatments with LZD were modified less frequently for clinical failure and this drug was the one most used in rescue therapies. This information indicates an appropriate use of these ATB in an important percentage of critically patients.

Objective: Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response., Material and Methods: One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrug-resistance-associated protein 1 (MRP1), and lung resistance protein (LRP)., Results: In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P< .01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma., Conclusions: Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.

Background: Those working in a hospital environment are exposed to different occupational risks, although more specifically biological ones. One of the major risks is that of exposure by airborne transmission, more specifically, tuberculosis. This study is aimed at providing a description and analysis of the results of the implementation of an evaluation and surveillance protocol following occupational exposure to Multiresistant mycobacterium bovis (MRMb)., Method: A male patient was diagnosed with MRMb infection at the Miguel Servet Hospital in Zaragoza in 1999 following ten days without respiratory isolation. During this period, he came into contact with 167 employees from different hospital departments. A surveillance and contact control protocol was prepared based on: completing a survey and undergoing an initial Mantoux (if the employee had previously tested negative for tuberculin), followed three months later by a chest X-ray and then a two-year clinical follow-up (check-ups every three months) for those having tested positive for tuberculin and no administering of chemoprophylaxis even though signs of infection were to have been found., Results: Information was gathered on 160 employees (96%). A total of 94 employees (59%) had previously undergone a Mantoux, seven (7) having had tuberculosis. It was necessary for a follow-up to be conducted on sixty-one (61) employees who tested positive (29 previously positive and 32 detected in the initial Mantoux). No employee who had tested negative on an initial Mantoux tested positive on repeated testing three months later nor showed any symptoms indicative of transmission during the follow-up period. Some variables, such as age or working in the Infectious Disease Unit were related, on a statistically significant basis, to follow-up being required., Conclusions: The risk of occupational transmission following contact with MRMb might be similar to M. Tuberculosis, although further experience would be required in order to confirm this fact. Early diagnosis and availing of a protocol for implementing measures aimed at preventing and controlling this type of occupational exposure are of importance.

In the last years, the incidence of the invasive infection by moulds has increased. Also, the characteristics of invasive mycosis are changing due to the description of new pathogenic species and also because strains and species resistant to antifungal drugs are appearing. The development of mould antifungal drug resistance is the inevitable and logical consequence of their clinical use, although the frequency and clinical relevance of this is unknown. In this text current mould antifungal drugs resistance mechanisms are reviewed. The study of molecular mechanisms of antifungal drug resistance is the most valuable strategy to resistance development control and also in helping to develop safer and more active molecules able to avoid them. In the meanwhile is important the correct use of the available tools: epidemiological surveillance of resistance emergence and to use all the efforts towards prompt diagnosis in order to accomplish an adequate and effective treatment.

Background: To present the epidemiology of the outbreak and the description of patients with infection or colonization of the respiratory tract caused by A. baumannii in an Internal Medicine ward., Methods: 20 consecutively patients hospitalized in the Internal Medicine ward were studied during 18 months with isolation of multiresistant A. baumanni in respiratory tract specimens with or without clinical signs of infection., Results: Starting on an index case, that was a patient coming from other hospital with diagnosis of nosocomial Acinetobacter pneumonia, we detected 20 patients. The age of the patients ranged from 48 to 95 years, with a mean of 71.4 years. Eighty percent were males. The clinical features were similar: advanced age, with chronic diseases (35 percent diabetics, 45 percent with chronic lung diseases), and use of broad-spectrum antibiotics agents, fundamentally third generation cephalosporin (70 percent), clarithromycin (55 percent) and quinolones (30 percent). 75 percent of patients were in the same ward. Eight (40 percent) of the patients with chronic lung diseases were subjects with COPD, two with asthma and chronic glucocorticoids treatment, and one with a sleep apnea. In four cases the isolation was considered a colonization. The mean stay was 26.15 days, and the mortality 40 percent., Conclusions: The nosocomial infection caused by Acinetobacter baumannii is responsible of a high morbi-mortality between the patients hospitalized in an Internal Medicine ward, and produce an increase in length of stay. It is necessary a combination of control measures to prevent the transmission in the hospital and the outbreak of new multiresistant strains.

Background: PRONARES (Programa Nacional de Vigilancia de Resistencia) is a national surveillance program for antimicrobial susceptibility, focused in different syndromes and among these, urinary tract infections. The work is done in a laboratory net that uses common protocols and whose data are centrally analyzed using the WHONET program., Aim: To analyze the pattern of antimicrobial susceptibility of agents causing urinary infections in children in the period 1997-1999., Material and Methods: In the study period, 5,525 strains were analyzed. Of these, 2,307 came from pediatric patients (1,495 hospitalized and 803 ambulatory)., Results: The most common causative agent was E. coli in 74.2% of cases, followed by Klebsiella spp in 8.2% and other agents in a lower frequency. Of E. coli strains, 74% were resistant to ampicillin, 52% to clotrimoxazole and 30% to first generation cephalosporins. These strains were sensitive to second and third generation cephalosporins, aminoglycosides, ciprofloxacin and nitrofurantoin. Strains from nosocomial or community infections had similar antimicrobial susceptibility. Klebsiella spp had a high rate of antimicrobial resistance (over 40%), that was even higher among nosocomial strains. It was 90% susceptible to ciprofloxacin and 100% to imipenem. All centers from which strains came had a similar pattern of susceptibility, with the exception of a pediatric center that had significantly higher resistance levels., Conclusions: The current therapeutic recommendations for urinary tract infections in children caused by E coli, are still pertinent, but the use of first generation cephalosporins must be cautious. The treatment of Klebsiella spp requires an individual antibiogram.

A survey of the changes in populations of heterotrophic bacteria, coliform microorganisms and S. meliloti was conducted in samples taken from the water irrigation channels of the Neuquén River (Argentina). Fifty-six water samples were collected during the spring-summer seasons of 1997-1999 years. Both the heterotrophic plate count bacterial and the number of coliforms oscillated between 110-5050 CFU/ml and 8-1400 CFU/100 ml, respectively, during the period this study was carried out. Fecal coliforms were detected in 91.1% of the water samples investigated. Moreover, the results showed that S. meliloti capable of nodulating alfalfa (Medicago sativa L.) Cuf 101 were present in 68% of the water samples and in effectiveness studies, no isolate out of 25 evaluated could be classified as superior N fixers. That is, they did not produce plants equal in weight to nitrate-grown plants (KNO3 0.05%). All the S. meliloti strains were resistant to novobiocin and bacitracin, while 72% of the microsymbionts demonstrated resistance to between seven and ten antibiotics. Results presented in this study showed that irrigation waters of the Neuquén river could act as dispersal agents of both ineffective S. meliloti strains and thermotolerant coliform bacteria.

Objectives: To determine the frequency of resistant Mycobacterium tuberculosis and the risk factors associated with resistance in the province of Castellón (Spain)., Material and Methods: This prospective study of M. tuberculosis sensitivity applied Canetti's method of proportions to all strains isolated in Castellón (n = 532) from January 1992 through December 1998 (7 years); 461 cases were new., Results: The overall frequency of resistant strains was 4.7% (25/532), of which 3.9% (18/461) were instances of primary resistance and 11.1% (7/63) were of secondary resistance. Three percent were resistant to isoniazid, 1.87% to rifampicin, 1.87% to streptomycin and 0.56% to ethambutol. Multiple drug resistance was found in 0.2% (1/461) of the new cases and 1.1% (6/532) overall. The presence of resistant M. tuberculosis was associated with a history of antituberculous treatment (OR = 3.14; p = 0.017) and the presence of one or more risk factors for tuberculosis (OR = 3.32; p = 0.066)., Conclusions: The overall rates of resistant M. tuberculosis and multiple drug resistance are low in the province of Castellón; however resistance is associated with higher mortality such that controlling some preventable risk factors might reduce the frequency of resistance.

Background: The aims of this multicenter study was to establish the level of primary and acquired drug resistance of M. Tuberculosis strains isolated in Barcelona and to identify possible risk groups using clinical data., Patients and Methods: All tuberculosis patients with isolation and identification of M. tuberculosis strains from October 1995 to September 1997 were included. Susceptibility tests isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide were performed using the Bactec 460 system and the proportions method on solid medium. Logistic progression was used for statistical analysis., Results: The total number of patients included was 1,749 (1,535 non-treated and 214 previously treated). Primary drug resistance was 5.7% (isoniazid 3.8%; rifampin 1.0%, streptomycin 2.1%, ethambutol 0.3% and pyrazinamide 1.0%). Acquired drug resistance was 20.5% (isoniazid 17.3%, rifampin 9.8%, ethambutol 1.9%, streptomycin 4.7% and pyrazinamide 6.5%). Primary drug resistance was associated with people over 60 years old and women., Conclusions: The low level of drug resistance enables antituberculosis treatment of non-treated patients to start with the standardised three-drug regimes except in the case of foreign people from countries with a high level of drug resistance. Susceptibility tests are recommended on all M. tuberculosis strains isolated, together with controlled studies of drug resistance surveillance.

Given the current concern about multiresistance to drugs in tuberculosis, the data from a large study in two different centers are presented. At the Hospital Universitario Reina Sofía de Córdoba 71,359 clinical isolates of Mycobacterium tuberculosis were processed and at the Centro de Referencia de Micobacterias 2,350 cultures were studied. The percentage of total multiresistance at the Hospital Universitario was 6&#37; from 1996-1998, and 6.7&#37; at the Centro de Referencia in 1998. Although these figures are high, they are lower than in previous years and could indicate the beginning of a decreasing trend, following years of increasing in the 1990s.

Objective: To identify the frequency of drug resistant tuberculosis and to determine risk factors for its development in five health districts in the State of Chiapas, Mexico., Design: A cross-sectional study., Emplacement: Primary care., Participants: Patients with pulmonary tuberculosis diagnosed between September 1 and December 31, 1995. Each patient responded to a questionnaire regarding epidemiological, diagnostic and treatment variables. Sputa were cultured, drug sensitivities and typing of micobacteria were obtained., Measurements and Main Results: There were 142 cases of pulmonary tuberculosis confirmed by acid fast smear. The frequency of resistant M. tuberculosis in 61 positive cultures was 24.2%. Of these, 33.3% was resistant to one drug and 66.7% at two or more drugs. Resistance to isoniazide and rifampicin together was present in 66.7% of the cases. The most frequent resistance, 86.7%, was to isoniazide. A history of multitreatments, either completed or not, resulted in a risk factor 6.48 times greater for drug resistance and patients with a history of abandoning treatment presented an increased risk factor of 5.71., Conclusions: Drug resistant tuberculosis y a serious problem in Chiapas that requires urgent attention if future control of the disease is to be maintained. The frequency of resistant tuberculosis is high, 24.2%, and the risk factors identified indicate a worsening of the situation with the accumulation of patients inadequeately treated without follow up until cure.

Actinomycetoma is a chronic disease that affects subcutaneous tissue. We present a case of a patient with abdominal actinomycetoma caused by Nocardia brasiliensis resistant to different treatments over several years, who also presented phagocyte immunodeficiency. He received two cycles (23 day cycles) of cefotaxime, 1 g every 8-h, and amikacin, 500 mg every 12 hours. Immunomodulation was carried out with levamisole 300 mg per week, during 4 weeks and bacterial antigen (at a concentration of 600,000,000 bacteria per mL), twice for a week during 20 months. The importance of susceptibility testing and immunological function investigation in this type of patients is discussed.

Background: The computer program WHONET generates a common database to analyze local or general antimicrobial resistance of bacteria. A surveillance of agents causing urinary tract infections in Chile has been performed using this program., Aim: To report the results after 12 months of urinary tract infection agent surveillance., Material and Methods: Since November, 1997, a surveillance of in vitro antimicrobial resistance, using agar diffusion techniques, has been performed in 20 to 40 bacterial strains per month, isolated from 11 hospitals in the country. Results have been analyzed using WHONET program., Results: In first 12 months, 3144 strains, 1625 coming from outpatients, have been studied. Seventy four percent of isolated strains were E coli, 19% were other enterobacteria, 4.1% were non fermenting bacilli and 2.1% were Gram (+) cocci. Sixty five percent of E coli strains were resistant to ampicillin, 11% to cefazolin, 2.5% to cefuroxime, 19% to ceftriaxone, 9% to ceftazidime, 4.2% to gentamicin 1.3% to amikacin, 5.6% to ciprofloxacin, 8.4% to grepafloxacin, 4.3% to nitrofurantoin and 43% to trimeproprim/sulphamethoxazole. Eighty two percent of other enterobacteria strains were resistant to ampicillin, 45.5% to cefazolin, 33.5% to cefuroxime, 26.6% to ceftriaxone, 21.5% to ceftazidime, 30.3% to gentamicin 17.2% to amikacin, 21% to ciprofloxacin, 16.3% to grepafloxacin, 48.2% to nitrofurantoin and 44.6% to trimeproprim/sulphamethoxazole. There were differences in betalactamic resistance among hospitals., Conclusions: Noteworthy is the high resistance rates to third generation cephalosporins, evidenced when the new cutoff values for E coli and Klebsiella spp are used. This national surveillance provides updated information on antimicrobial resistance of agents causing urinary tract infections.

Background: The recent emergence of glycopeptide-resistant enterococci limits the treatment of enterococcal infections. The aim of this study was to evaluate the in vitro activity of a new streptogramin, quinupristin/dalfopristin, against 30 clinical isolates of vancomycin-resistant enterococci and compared with those of other 15 antimicrobials., Material and Methods: Enterococci were identified by using Rapid ID 32 Strep system. Genotyping of the isolates was performed by PCR. The MICs of quinupristin/dalfopristin were determined by the agar dilution technique recommended by the NCCLS. Susceptibilities to the rest of antibiotics tested (teicoplanin, ampicillin, penicillin, imipenem, doxycicline, chloramphenicol, gentamicin, streptomycin, rifampin, levofloxacin, fleroxacin, trovafloxacin, sparfloxacin, pefloxacin and clinafloxacin) were determined by using the E test. beta-lactamase production was examined with nitrocefin disks., Results: Quinupristin/dalfopristin has demonstrated excellent activity against Enterococcus faecium (MIC90' 2 micrograms/ml). Enterococcus faecalis was considerably less susceptible than E. faecium, at concentration of 4 micrograms/ml inhibited only 31% of tested strains. For doxycicline 77% of strains were susceptible. Only five isolates were susceptible to clinafloxacin; the other quinolones tested displayed poor activity. Resistance to chloramphenicol was detected in 47% of isolates. None of the isolates produced beta-lactamase., Conclusions: This study indicates that vancomycin-resistant enterococci are often concomitantly resistant to multiple antibiotics. Quinupristin/dalfopristin was the most active agent tested against E. faecium strains. On the basis of these results quinupristin/dalfopristin could be a therapeutic option for the treatment of vancomycin-resistant E. faecium infections.

The presence of multidrug efflux-pump systems in bacteria showing resistance to various drugs is increasingly reported in the literature. These systems are inducible by compounds such as salicylate and can thus be involved in situations of phenotypic resistance at the point of the infection which would otherwise be barely detectable under standard laboratory testing conditions. On the other hand, mutants which overproduce efflux-pumps and show increased levels of antibiotic resistance are easily selectable. It has been shown that inactivation of efflux-pump determinants produces an increased susceptibility to different antibiotics as well as prevents the emergence of mutants with a high-level antibiotic resistance to drugs such as quinolones. The search for efflux-pump inhibitors to be used in combination with other currently used antibiotics is therefore an important task for the renewal of the antibacterial therapeutic armamentarium. No efflux-pump inhibitors are commercially available as yet. However, several companies are in the process of working on their development. In this review, we discuss four possible targets that could be useful in the screening of inhibitors of efflux-pump systems in bacteria.