Outcomes by sex following treatment initiation with darunavir/cobicistat in a large Spanish cohort of the CODAR study (GeSIDA 9316).

BACKGROUND: Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies. OBJECTIVES: Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens. METHODS: A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent. RESULTS: Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes. CONCLUSIONS: No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.

Successful treatment of postsurgical meningitis caused by Bacillus cereus: a case report and literature review.

Bacillus cereus is a spore-forming, gram-positive bacterium that is ubiquitous in the environment. Central nervous system involvement with B. cereus is rare. Despite aggressive treatment with broad-spectrum antibiotics and using them appropriately, the mortality is high. A 72-year-old patient suffered a central nervous system infection associated with postsurgical meningitis and was successfully treated with a novel antibiotic therapy. This study includes the first case report of postsurgical B. cereus meningitis in the last ten years. It provides a different line of treatment to the previous ones.

Evaluation of the in-vitro cidal activity and toxicity of a novel peroxygen biocide: 2-butanone peroxide.

The monomer of 2-butanone peroxide is a novel peroxygen derivative with potential use as biocide in the hospital environment. The aim of this study was to test the biocidal activity of different concentrations of the compound against American Tissue Culture Collection strains from 11 different micro-organisms, including bacteria, mycobacteria, spores, fungi and virus, following the European Standard guidelines. Toxicity tests were also carried out following United States Environmental Protection Agency Standards. 2-Butanone peroxide exhibited biocidal activity at 0.12% against Legionella pneumophila, at 0.5% against Escherichia coli, Pseudomonas aeruginosa and Enterococcus hirae, and at 1% against Staphylococcus aureus after 5 min contact at room temperature. Mycobactericidal activity was obtained at 0.5% after 60 min contact at 20 degrees C, and sporicidal activity was obtained at 4% after 60 min at 40 degrees C. Good fungicidal (against yeasts and moulds) and virucidal (adenovirus and poliovirus) activities were obtained at 0.5% after 60 min contact. Toxicity assessment showed negative results in the acute dermal irritation test, acute eye irritation test and acute oral toxicity test. The skin sensitisation test was negative. The safety profile in the toxicity tests and the basic cidal activity against the strains tested suggest that 2-butanone peroxide in the control of hospital infections.

beta-lactam susceptibility of Escherichia coli isolates from urinary tract infections exhibiting different resistance phenotypes.

Susceptibility to beta-lactams was determined in 203 recent Spanish E. coli isolates from urinary tract infections exhibiting different resistance phenotypes: a) susceptible (n = 60); b) quinolone-resistant (n = 45); c) penicillinase (n=64); d) hyperproduction of penicillinase (n=8); e) inhibitor resistant TEM (IRT) (n=18), and f) extended spectrum betalactamase (ESBL) (n=8).Minimum inhibitory concentration (MIC) determination by agar dilution and susceptibility tests for ESBL detection by macrodilution were performed following CLSI recommendations. All the beta-lactams tested showed high activity against susceptible and penicillinase phenotypes, with close to 100 % susceptibility. Hyperproduction of penicillinase increased MIC90 values for all antibiotics except for meropenem, with 100% resistance to cefuroxime and amoxicillin/clavulanic acid, and 100% susceptibility to cefotaxime, piperacillin/tazobactam and meropenem. All the antibiotics, except for amoxicillin/clavulanic acid, exhibited high activity against IRT. Meropenem, cefminox and piperacillin/tazobactam exhibited the highest activity against ESBL, followed by amoxicillin/clavulanic acid. The most active compound among the parenteral antibiotics was meropenem, regardless of the resistance phenotype. Among the oral antibiotics, the most active compound was cefditoren with the exception of ESBL where amoxicillin/clavulanic acid where the MIC90 value was one dilution lower.

The Meropenem Yearly Susceptibility Test Information Collection antimicrobial susceptibility program in Spain: a 5-year analysis.

The Meropenem Yearly Susceptibility Test Information Collection program is a global study providing in vitro surveillance data on antimicrobial susceptibility in centers prescribing meropenem. This study summarizes data on the activity of meropenem and 5 comparators against 4022 clinical isolates from 7 centers in Spain (1999-2003). Those bacteria intrinsically resistant to meropenem were excluded. Among Enterobacteriaceae, 100% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem. Escherichia coli and Klebsiella pneumoniae susceptibilities to carbapenems were 100% and > or =98%, respectively. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were 3.8% of isolates, and all of them were susceptible to meropenem. Ciprofloxacin resistance in E. coli was around 20%. Meropenem and piperacillin/tazobactam were the most active agents against Pseudomonas aeruginosa. Acinetobacter baumannii were 61-90% susceptible to carbapenems, but only 6-21% susceptible to ciprofloxacin. In this period, around 100% of oxacillin-susceptible staphylococci were susceptible to meropenem. There was no significant decrease in susceptibility to the carbapenems throughout the 5-year period. The clinical use of meropenem in 7 Spanish centers did not increase bacterial resistance to this agent in the microorganisms evaluated.

Quinolone resistance in female outpatient urinary tract isolates of Escherichia coli: age-related differences.

During a 1-year period, from November 2003 to October 2004, urinary Escherichia coli isolates were collected from 20 clinical microbiology laboratories across Spain. The main objective was to assess the resistance of E. coli to the antimicrobials most commonly prescribed for community-acquired urinary tract infections depending on the patient's age. A total of 2,230 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing using an agar dilution method. A two-sided chi-squared test was used to assess the differences in resistance between age groups (< or =65 and >65 years). E. coli resistance was found to be more common to ampicillin (52.1%), cotrimoxazole (26%) and quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime axetil and fosfomycin were below 3%. In women older than 65 years, resistance to ciprofloxacin reached up to 29% compared with 13% of those in the under 65 age group (p <0.001). For cotrimozaxole, rates were 32% vs. 23% (p <0.001) and for ampicillin 56% vs. 50% (p=0.02), respectively. It was concluded that fosfomycin, amoxicillin-clavulanic acid and cefuroxime axetil are the most suitable antimicrobials for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Being older than 65 years of age was associated with higher resistance rates to ciprofloxacin (29%). These results should be considered when recommending empirical therapy for acute cystitis in women.

Antimicrobial susceptibility of clinical Escherichia coli isolates from uncomplicated cystitis in women over a 1-year period in Spain.

High usage of antibiotics in Spain has led to an increase in resistance in urinary Escherichia coli isolates in different geographic regions. The problem of resistance in urinary E. coli in Spain was investigated by gathering a large number of isolates from 20 different sites nationwide over a 1-year period from November 2003 to October 2004 in a large population of women. The objectives of this study were to assess the resistance to the antibiotics most commonly prescribed for community-acquired urinary tract infections (UTIs), according to age and different geographical areas of Spain, and to evaluate the potential association between geographical differences in quinolone consumption and resistance to E. coli. A total of 2,292 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing. Of these, 2,230 isolates were available for the age analysis. A two-sided chi2 test was used to identify differences in resistance between age groups. Antibiotic units per province were purchased from IMS and consumption was expressed in units per 1,000 people per year. Univariate correlation (Pearson coefficient) between resistance to ciprofloxacin and quinolone consumption was calculated using a two-sided p-value. Resistance shown by E. coli was more common to ampicillin (52.1%) and cotrimoxazole (26%), followed by quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime-axetil and fosfomycin was less than 3%. In the subgroup of women aged >65 years, resistance to ciprofloxacin was 29% compared to 13% for the subgroup of women <65 years (p<0.001). For these same subgroups, resistance rates were 32% vs. 23% for cotrimoxazole (p<0.001) and 56% vs. 50% for ampicillin (p=0.02), respectively. Statistically significant correlations were found between consumption of quinolones and E. coli resistance to ciprofloxacin (r=0.5; p=0.025). Resistance of E. coli isolates to quinolones varied significantly according to geographical areas, ranging from a high of 16.5% and 16.6% in the southern and eastern regions of Spain, respectively, to a low of 8% in the north in women aged <65 years. Additionally, the susceptibility to quinolones of E. coli isolates recovered from women aged >65 years was significantly lower across all regions of Spain than that of isolates recovered from younger women. Fosfomycin, amoxicillin/clavulanic acid and cefuroxime-axetil are the most suitable antibiotics for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Higher resistance rates to ciprofloxacin were associated with being aged 65 years and over. These data need to be considered when recommending empirical therapy for acute cystitis.

Discrepancy between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: multicentre study in the primary care setting.

A national multicentre prevalence study was undertaken to determine the bacterial strains associated with mild-to-moderate acute exacerbations of chronic bronchitis (AECB) in the primary care setting and the susceptibility of isolated pathogens to different antimicrobials usually prescribed to these patients. All samples were processed by a central reference laboratory. Microdilution tests were carried out to establish the minimum inhibitory concentration (MIC) of various antimicrobials. A double-disk test was performed to establish the macrolide resistance phenotype in Streptococcus pneumoniae. Tests to detect the presence of beta-lactamase in Haemophilus influenzae and Moraxella catarrhalis and polymerase chain reaction to detect the presence of ermB and mefA genes in S. pneumoniae isolates were also performed. A total of 1537 patients were included in the trial and 468 microorganisms were isolated from sputum samples, with the most frequent isolates being S. pneumoniae (34.8%), M. catarrhalis (23.9%) and H. influenzae (12.6%). Resistance rates of pneumococci were 47.2% for penicillin, 1.2% for amoxicillin, 34.3% for macrolides (87.5% of which showed high-level resistance), 13.6% for cefuroxime/axetil and 4.2% for levofloxacin. No bacterial isolates showed resistance to telithromycin. Empirical antibiotic treatment was prescribed to 98.3% of patients, including macrolides to 36.6%, amoxicillin with or without clavulanic acid to 32.3% and fluoroquinolones to 16.1%. In conclusion, S. pneumoniae was the most frequently isolated bacteria in patients with mild-to-moderate AECB. Despite the high rates of resistance of pneumococci to macrolides, they continue to be the most widely used antibiotics in primary care to treat AECB.

The utility of polymerase chain reaction (PCR) in the diagnosis of pulmonary tuberculosis.

A fragment of DNA of 123 bp belonging to insertion sequence IS6110, specific of Mycobacterium tuberculosis complex, was amplified by polymerase chain reaction (PCR) of respiratory samples, for the diagnosis of pulmonary tuberculosis. A total of 314 samples (286 sputum and 28 bronchoalveolar lavages) from 242 patients were evaluated by PCR, and the results were compared with the those obtained by acid-fast-stained smears, culture, and clinical diagnosis. Mycobacterium tuberculosis was detected by PCR in 102 of 105 patients with clinical diagnosis of pulmonary tuberculosis. All smear and culture-positive samples were PCR positive. The sensitivity of PCR, culture, and staining was 97%, 88%, and 65%, respectively, and the specificity was 100% in all cases. In ten patients with old residual lesions, but no active disease, M tuberculosis genome was detected by PCR. In our experience, PCR proved to be a useful method for the rapid diagnosis of pulmonary tuberculosis.

New directions in diagnostics.

BACKGROUND: Infectious diseases are still a significant clinical problem in children, and accurate identification of the causal pathogen plays an important role in clinical management. The availability of an etiologic diagnosis enables the clinician to make appropriate therapeutic decisions and to avoid the indiscriminate use of antibiotics. The availability of a microbiologic diagnosis and the susceptibility profile of the pathogen allows the prompt initiation of suitable antibiotic treatment. However, the usefulness of current culture and identification methods is limited by the time needed and by their sensitivity and specificity. Also some microorganisms are difficult or impossible to grow in the laboratory. OBJECTIVES: To review the newer and more rapid diagnostic techniques that are becoming available and consider their application in the diagnosis of specific infections. DISCUSSION: Immunoassays have many advantages and it is hoped that new optical immunoassays will overcome the problems of poor sensitivity. Nucleic acid amplification techniques have enormous potential in the diagnosis of infectious diseases because of their high specificity and sensitivity and the speed with which the results can be obtained. However, there are still a number of difficulties that must be overcome before these methods can be widely adopted for routine testing. These techniques may be particularly relevant for the rapid diagnosis of streptococcal pharyngitis, where throat culture is slow and beset by a number of factors which reduce its accuracy. Polymerase chain reaction methods have been developed for many respiratory pathogens, including Mycoplasma pneumoniae, Chlamydia pneumoniae and Mycobacterium tuberculosis, and are likely to play an increasingly important part in diagnosis. In bacterial meningitis culture is still the gold standard and molecular techniques have not yet been developed to the point where they can be used in routine diagnosis. Nucleic acid techniques are likely to be very valuable in the diagnosis of streptococcal pharyngitis and viral central nervous system infections in the near future.

Evolution of penicillin and erythromycin co-resistance in Streptococcus pneumoniae in Spain.

The temporal dynamics of penicillin and erythromycin co-resistance in Streptococcus pneumoniae based on two extensive multicentre Spanish surveillance SAUCE studies (1996-1997 and 1998-1999) is presented. Erythromycin resistance among penicillin non-susceptible isolates seems to have reached a limit as evidenced by a null increase between the two surveys, whereas it is growing among penicillin-susceptible pneumococci.

[The mycoplasmas isolated from respiratory specimens]. / Micoplasmas aislados de muestras respiratorias.

BACKGROUND: Mycoplasma pneumoniae is the species that is considered pathogen for respiratory tract. Other species, M. hominis and U. urealyticum, have been isolated from respiratory specimens and its aetiological relation with respiratory infections is not clear. METHODS: In this study, mycoplasma from respiratory specimens have been isolated from HIV infected patients, patients suffering from chronic bronchitis and patients with respiratory infections without any underlying disease, using SP-4 media and being identified with glucose fermentation test, guinea pig blood cells adsorption, tetrazolium reduction, urea test, arginine test, and antigenic study by an immunoassay on the colonies grown on SP-4 solid medium. RESULTS: M. hominis has been the species most frequent isolated, mainly from patients without any underlying disease and from HIV infected patients, and less frequently from patients suffering from chronic bronchitis, the differences between both groups being significative. Other Mycoplasma, no identified at he species level, have been isolated although without any significative differences. In only one case U. urealyticum has been isolated. CONCLUSIONS: No M. pneumoniae isolation was obtained.

[Use of DNA amplification to diagnose cytomegalovirus in HIV seropositive patients]. / Utilidad de la amplificación de DNA para diagnosticar citomegalovirus en la población seropositiva para el virus de la inmunodeficiencia humana.

BACKGROUND: Cytomegalovirus (CMV) infection is common among HIV seropositive patients, being difficult to diagnose because it requires cell cultures not available in all hospitals. DNA amplification is being applied for diagnosis of infectious diseases with an increase in sensitivity and specificity with respect to previous laboratory methods. METHODS: Polymerase chain reaction (PCR) has been used in comparison with culture isolation, early antigen detection to diagnose CMV infection in 22 HIV infected patients, that suffered from symptoms compatible with CMV infection at the present time, and in other 5 patients suffering from Kaposi sarcoma. PCR was done with primer for CMV IE genomic region. The amplified sequences were detected after hybridization with a gamma-P-32 labelled probe, followed by electrophoresis in a 5% polyacrylamide gel and autoradiography. RESULTS: The PCR allows to detect CMV genome in cases in which other tests are negatives, in blood as well as in urine, included those patients suffering only from febrile symptoms or with other associated pathogen. CONCLUSIONS: PCR is a sensitive method to detect CMV, although it does not establish the responsibility of CMV in HIV infected patients.

[Applications of the polymerase chain reaction (PCR) to the diagnosis of central nervous system infections]. / Aplicaciones de la reacción en cadena de polimerasa (PCR) al diagnóstico de infecciones del sistema nervioso central.

The utility of polymerase chain reaction (PCR) is described for the diagnosis in three patients suffering from central nervous system infections, tuberculous meningitis, herpetic encephalitis and cerebral toxoplasmosis. PCR was performed in the cerebrospinal fluid after processing the specimen by two methods, proteinase K digestion and phenol extraction of DNA. Amplification was realized using primers previously described that amplify specific DNA fragments of each microorganisms (insertion sequence IS6110 of Mycobacterium tuberculosis, B1 gene of Toxoplasma gondii, and DNA polymerase gene of Herpes simplex virus). In all three cases, PCR was positive after amplification of the specimen extracted with proteinase K, as well as when a complete DNA extraction with phenol was realized. In all cases a band of amplified products was observed in agarose gels. In conclusion, in all three patients described, PCR would had allowed the diagnosis in seven hours, and PCR should be consider a rapid sensitive and relatively simple method.

[Non-gonococcal urogenital infections: etiology]. / Infecciones urogenitales no gonocócicas: etiología.

1,109 patients suffering from non-gonococcal urogenital infections have been studied. 63.4% of the patients had genital discharge. Microorganisms were found in 685 patients (61.8%), only one agent being isolated in 73.6% and two in 22.1% of the cases respectively. The rest of the patients had an association of three or more microorganisms. In women, the most frequently identified microorganism was Candida sp (29.9%), followed by U. urealyticum (20.5%) and G. vaginalis (19.7%). In men, U. realyticum (40.1%) was the most frequent followed by C. Trachomatis (21.4%) and M. hominis (16.6%).

[Non-gonococcal urethritis caused by Chlamydia trachomatis: factors affecting its incidence]. / Uretritis no gonocócica por Chlamydia trachomatis: factores que influyen en su incidencia.

A retrospective study to investigate the relationship between the isolation of Chlamydia trachomatis and other factors occurring in 146 patients suffering of non-gonococcal urethritis, has been released 39 being positive for C. trachomatis. The relationship between the isolation of C. trachomatis and previous antibiotic treatment, age, sexual different contacts in the last month and year has been studied. The main feature affecting the isolation is the absence of antimicrobial therapy a previously to the specimen collection and being performed after four days post-contact.