Neopeltolide and its synthetic derivatives: a promising new class of anticancer agents.

Being the first or second cause of death worldwide, cancer represents the most significant clinical, social, and financial burden of any human illness. Despite recent progresses in cancer diagnosis and management, traditional cancer chemotherapies have shown several adverse side effects and loss of potency due to increased resistance. As a result, one of the current approaches is on with the search of bioactive anticancer compounds from natural sources. Neopeltolide is a marine-derived macrolide isolated from deep-water sponges collected off Jamaica's north coast. Its mechanism of action is still under research but represents a potentially promising novel drug for cancer therapy. In this review, we first illustrate the general structural characterization of neopeltolide, the semi-synthetic derivatives, and current medical applications. In addition, we reviewed its anticancer properties, primarily based on in vitro studies, and the possible clinical trials. Finally, we summarize the recent progress in the mechanism of antitumor action of neopeltolide. According to the information presented, we identified two principal challenges in the research, i) the effective dose which acts neopeltolide as an anticancer compound, and ii) to unequivocally establish the mechanism of action by which the compound exerts its antiproliferative effect.

Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis.

INTRODUCTION: Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation. Therefore, we aimed to determine the impact of macrolide-based therapy on long-term mortality in this population. METHODS: Registered patients in the MIMIC-IV database 16 years or older and admitted to the ICU due to CAP were included. Multivariate analysis, targeted maximum likelihood estimation (TMLE) to simulate a randomised controlled trial, and survival analyses were conducted to test the effect of macrolide-based treatment on mortality six-month (6 m) and twelve-month (12 m) after hospital admission. A sensitivity analysis was performed excluding patients with Pseudomonas aeruginosa or MRSA pneumonia to control for Healthcare-Associated Pneumonia (HCAP). RESULTS: 3775 patients were included, and 1154 were treated with a macrolide-based treatment. The non-macrolide-based group had worse long-term clinical outcomes, represented by 6 m [31.5 (363/1154) vs 39.5 (1035/2621), p < 0.001] and 12 m mortality [39.0 (450/1154) vs 45.7 (1198/2621), p < 0.001]. The main risk factors associated with long-term mortality were Charlson comorbidity index, SAPS II, septic shock, and respiratory failure. Macrolide-based treatment reduced the risk of dying at 6 m [HR (95% CI) 0.69 (0.60, 0.78), p < 0.001] and 12 m [0.72 (0.64, 0.81), p < 0.001]. After TMLE, the protective effect continued with an additive effect estimate of - 0.069. CONCLUSION: Macrolide-based treatment reduced the hazard risk of long-term mortality by almost one-third. This effect remains after simulating an RCT with TMLE and the sensitivity analysis for the HCAP classification.

Implementación de un método molecular para la identificación de Mycoplasma pneumoniae resistente a macrólidos / Implementation of a molecular method for the detection of macrolide-resistant Mycoplasma pneumoniae

Introducción: Mycoplasma pneumoniae es causa frecuente de infecciones respiratorias en niños y jóvenes. Los macrólidos son la primera línea de tratamiento. La rápida emergencia de resistencia a estos antimicrobianos ha motivado el desarrollo de métodos moleculares para su detección en muestras clínicas positivas a este patógeno. Objetivo: Implementar un método de reacción en cadena de la polimerasa en tiempo real (RT-PCR) para la detección de resistencia a macrólidos a partir de muestras clínicas positivas a M. pneumoniae. Métodos: Se implementó una RT-PCR para la detección de las mutaciones A2058G y A2059G en el ARNr 23S de M. pneumoniae. Se analizaron 24 muestras clínicas positivas a M. pneumoniae, que provenían de pacientes con síntomas respiratorios. Se evaluó la sensibilidad, especificidad, repetibilidad y reproducibilidad de la RT-PCR. Resultados: La RT-PCR mostró un 100 % de especificidad para M. pneumoniae y un 92 % de sensibilidad, con un límite de detección de 2 copias/µL, que equivale a 10 copias/reacción. Además, se demostró la reproducibilidad y repetibilidad de estos resultados. Se obtuvo una correcta identificación de los genotipos salvaje y mutante, correspondientes a cada control. De las muestras clínicas positivas a M. pneumoniae, el 77,3 % (17/22) se identificó como sensible a macrólidos y el 22,7 % (5/22) como resistente. Conclusiones: La alta sensibilidad y especificidad del método de RT-PCR implementado permite que el Laboratorio Nacional de Referencia de Micoplasmas del Instituto de Medicina Tropical Pedro Kourí cuente con un método eficaz para el diagnóstico de M. pneumoniae resistente a macrólidos.

Introduction: Mycoplasma pneumoniae is a common cause of respiratory track infections in children and young adults. Macrolides are the first-line treatment. The rapid emergence of resistance to these antimicrobials has motivated the development of molecular methods for their detection in clinical samples positive for this pathogen. Objective: To implement a real-time polymerase chain reaction (RT-PCR) method for the detection of macrolide resistance in M. pneumoniae positive clinical samples. Methods: An RT-PCR was implemented to detect mutations A2058G and A2059G in 23S rRNA of M. pneumoniae. M. pneumoniae positive clinical samples from 24 patients with respiratory symptoms were analyzed. Sensitivity, specificity, repeatability and reproducibility of the RT-PCR assays were evaluated. Results: The RT-PCR assays showed 100% specificity to M. pneumoniae, and 92% sensitivity with a detection limit of 2 copies/µL, equivalent to 10 copies/reaction. Moreover, the repeatability and reproducibility of these results were demonstrated. Wild and mutant genotypes associated to each control were properly identified. Of the clinical samples positive for M. pneumoniae, 77.3% (17/22) were macrolide-sensitive and 22.7% (5/22) were macrolide-resistant. Conclusions: The high sensitivity and specificity of the RT-PCR method implemented provides the National Reference Laboratory of Mycoplasmas of the Institute of Tropical Medicine Pedro Kourí with an effective method for the diagnosis of macrolide-resistant M. pneumoniae.

Increase of Macrolide-Resistance in Streptococcus pneumoniae Strains After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Lima, Peru.

Streptococcus pneumoniae upper respiratory infections and pneumonia are often treated with macrolides, but recently macrolide resistance is becoming an increasingly important problem. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the National Immunization Program of Peru in 2015. This study aimed to evaluate the temporal evolution of macrolide resistance in S. pneumoniae isolates collected in five cross-sectional studies conducted before and after this vaccine introduction, from 2006 to 2019 in Lima, Peru. A total of 521 and 242 S. pneumoniae isolates recovered from nasopharyngeal swabs from healthy carrier children < 2 years old (2 carriage studies) and samples from normally sterile body areas from pediatric patients with invasive pneumococcal disease (IPD) (3 IPD studies), respectively, were included in this study. Phenotypic macrolide resistance was detected using the Kirby-Bauer method and/or MIC test. We found a significant increase in macrolide resistance over time, from 33.5% to 50.0% in carriage studies, and from 24.8% to 37.5% and 70.8% in IPD studies. Macrolide resistance genes [erm(B) and mef(A/E)] were screened using PCR. In carriage studies, we detected a significant decrease in the frequency of mef(A/E) genes among macrolide-resistant S. pneumoniae strains (from 66.7% to 50.0%) after introduction of PCV13. The most common mechanism of macrolide-resistant among IPD strains was the presence of erm(B) (96.0%, 95.2% and 85.1% in the 3 IPD studies respectively). Macrolide resistance was more common in serotype 19A strains (80% and 90% among carriage and IPD strains, respectively) vs. non-serotype 19A (35.5% and 34.4% among carriage and IPD strains, respectively). In conclusion, S. pneumoniae macrolide resistance rates are very high among Peruvian children. Future studies are needed in order to evaluate macrolide resistance trends among pneumococcal strains, especially now after the COVID-19 pandemic, since azithromycin was vastly used as empiric treatment of COVID-19 in Peru.

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis.

BACKGROUND: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. METHODS: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. RESULTS: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (-38 to -42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer-Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. CONCLUSIONS: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.

Influence of levofloxacin and clarithromycin on the structure of DPPC monolayers.

Research on lipid/drug interactions at the nanoscale underpins the emergence of synergistic mechanisms for topical drug administration. The structural understanding of bio-mimetic systems employing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a lung surfactant model mixed with antibiotics, as well as their biophysical properties, is of critical importance to modulate the effectiveness of therapeutic agents released directly to the airways. In this paper, we investigate the structural details of the interaction between Levofloxacin, 'a respiratory quinolone', and the macrolide Clarithromycin, with DPPC monolayers at the air-water interface, using a combination of Brewster angle microscopy, polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), surface pressure isotherms and neutron reflectometry (NR) to describe the structural details of this interaction. The results allowed association of changes in the π-A isotherm profile with changes in the molecular organization and the co-localization of the antibiotics within the lipid monolayer by NR measurements. Overall, both antibiotics are able to increase the thickness of the acyl tails in DPPC monolayers with a corresponding reduction in tail tilt as well as to interact with the phospholipid headgroups as shown by PM-IRRAS experiments. The effects on the DPPC monolayers are correlated with the physical-chemical properties of each antibiotic and dependent on its concentration.

First detection and characterization of macrolide-resistant Mycoplasma pneumoniae strains in Cuba.

OBJECTIVES: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in humans. Treatment of infections can be complicated by the occurrence of macrolide resistant strains. The study was conducted to evaluate the presence of resistant strains in Cuba and to determine the corresponding genotypes. METHODS: DNA of M. pneumoniae isolates and positive respiratory tract specimens collected in the years 2012 and 2017 were tested for resistance-associated mutations of 23S rRNA. In addition, strain types (P1 and MLVA) were determined. RESULTS: Macrolide resistance mutations were confirmed in 5 out of 27 strains (18.5%). Whereas both P1 subtypes 1 and 2 as well variants V2a and V2c were identified, only two MLVA types (4/5/7/2 and 3/5/6/2) could be found. CONCLUSIONS: During both sampling years, circulation of macrolide resistant strains was demonstrated. No association of resistance with a particular P1/MLVA type was found. Future longitudinal sampling to monitor prevalence of macrolide resistance of M. pneumoniae is recommended to verify the resistance pattern of this important pathogen of human respiratory tract infections.

Multilocus Sequence Typing of Treponema pallidum subsp. pallidum in Cuba From 2012 to 2017.

BACKGROUND: The increased prevalence of syphilis in Cuba prompted us to map the circulating Treponema pallidum subsp. pallidum allelic profiles in this geographic region. METHODS: Samples were collected from 2012 to 2017, from 83 male patients with ulcers or skin lesions, and were examined using multilocus sequence typing. Additionally, we analyzed the 23S rDNA and 16S rDNA regions for the presence of possible mutations leading to macrolide and tetracycline resistance. RESULTS: Among 94% of fully typed strains, we found 7 different allelic profiles, of which 4 had not been previously described. More than 87% of patients were infected with the T. pallidum SS14-like group and only 8.2% with T. pallidum Nichols-like group. As in other countries, the 1.3.1 allelic profile (ie, SS14-like) was the most common. In addition, 1 of the newly described allelic profiles represents T. pallidum strains that arose by recombination events between members of different T. pallidum subgroups. More than 90% of patients were infected with treponemes harboring the A2058G mutation. However, we found no potential tetracycline-resistant T. pallidum mutations. CONCLUSIONS: Our results suggest that, in Cuba, tetracycline antibiotics could be used to treat syphilis in penicillin-allergic patients instead of macrolides.

Macrolide-resistant Mycoplasma genitalium infections in Cuban patients: an underestimated health problem.

BACKGROUND: The increasing prevalence of macrolide resistant Mycoplasma genitalium is a major concern worldwide. In Cuba, several cases of clinical treatment failure with 1 g single dose and extended azithromycin regimen have been detected and the aim of the present investigation was to retrospectively determine the prevalence of macrolide-resistance mediating mutations (MRMM) in M. genitalium-positive samples conserved at the Cuban National Reference Laboratory of Mycoplasma Research between 2009 and 2016. METHODS: A total of 280 positive DNA extracts were analysed by a 5' nuclease assay for detection of M. genitalium MRMM. Ten urogenital specimens from patients with azithromycin treatment failure and MRMM were inoculated in Vero cell to obtain the isolates for subsequent determination of antimicrobial susceptibility. RESULTS: The overall prevalence of MRMM was 32%. No MRMM was detected in samples collected between 2009 and 2013 but since 2014 a dramatic increase to 90% (95% CI, 76-96%) in 2016 was seen. Three new M. genitalium isolates were isolated in Vero cell cultures and confirmed phenotypic resistance to macrolides in a cell-culture assisted susceptibility test. Preliminary observations suggest that combination therapy with levofloxacin and doxycycline may represent an affordable option for treatment of macrolide resistant M. genitalium infections. CONCLUSIONS: This investigation showed the rapid emergence and high prevalence of MRMM in M. genitalium-infected patients in Cuba and confirmed the phenotypic resistance in isolates carrying MRMM. We suggest that Cuban guidelines for sexually transmitted infections are modified to include testing for M. genitalium and detection of MRMM in patients with failure of syndromic treatment, to ensure that in these cases, the treatment will be guided by etiologic diagnosis.

Genotyping and macrolide resistance of Mycoplasma pneumoniae identified in children with community-acquired pneumonia in Medellín, Colombia.

OBJECTIVES: The aim of this study was to describe the genotypes and the main characteristics of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae in hospitalized children in Medellín and neighboring municipalities during the period 2011-2012. METHODS: The M. pneumoniae genotype was determined by PCR and sequencing of the p1 and 23S rRNA genes from induced sputum samples and nasopharyngeal swabs (NPS). Samples were obtained from children with CAP who were hospitalized in 13 healthcare centers. In addition, a spatio-temporal analysis was performed to identify the potential risk areas and clustering of the cases over time. RESULTS: A variant of type 2 was the dominant genotype in the induced sputum (96.1%) and NPS (89.3%) samples; the type 1 variant was identified in 3.9% and 10.7% of these samples, respectively. No strains with mutations in the 23S rRNA gene associated with macrolide resistance were found. The cases in Medellín were mainly concentrated in the northeastern areas and western districts. However, no temporal relationship was found among these cases. CONCLUSIONS: A variant of type 2 of M. pneumoniae prevailed among children with CAP during the study period. No strains with mutations associated with macrolide resistance were found.

Improving Production of Tacrolimus In Streptomyces Tacrolimicus (ATCC 55098) Through Development of Novel Mutant by Dual Mutagenesis

ABSTRACT Tacrolimus is a polyketide macrolide produced by Streptomyces species which is widely used as anti-fibrotic agent and potent immunosuppressant. In this article dual mutagenesis approach using mutagens (NTG+EMS+UV) was used to develop a mutant strain of Streptomyces tacrolimicus (ATCC 55098) for higher tacrolimus production and this strain showed higher tacrolimus production at 82.5 mg/l. Interestingly; addition of L-Lysine (0.2 g/l) into the production medium further enhanced the tacrolimus production to ~102 mg/l at 7-L fed-batch bioreactor. To the best of our knowledge this is the first report mentioning efficient strain development for higher production of tacrolimus using dual mutagenesis. The obtained data presents an impressive model for higher production of tacrolimus and enhanced our understanding regarding improvement in production capacity of tacrolimus in Streptomyces tacrolimicus.

Susceptibility profile of Brazilian Rhodococcus equi isolates against azithromycin, clarithromycin and erythromycin / Perfil de susceptibilidade de isolados brasileiros de Rhodococcus equi frente à azitromicina, claritromicina e eritromicina

Rhodococcus equi infection treatment is usually a macrolide (azithromycin - AZM, clarithromycin - CLR and erythromycin - ERY) and rifampicin combination. However, resistance cases have been reported, especially for ERY. In view of the need of a study about Brazilian isolates susceptibility profile, this study aimed to characterize the minimum inhibitory concentration (MIC) of the macrolides - AZM, CLR and ERY - against 44 R. equi isolates. It was found all isolates CLR and AZM sensitive; however, for ERY, 27% (12/44) were classified as intermediate sensitivity. R. equi Brazilian isolates used here showed a large susceptibility profile, except against ERY, for which it was observed some resistance evidence. In order to avoid failures in the equine rhodococcosis therapy it was highlighted the importance of microbiological culture and antimicrobial susceptibility testing in vitro before beginning treatment.(AU)

No tratamento de infecções por R. equi, usualmente emprega-se uma combinação de macrolídeos (azitromicina - AZI, claritromicina - CLARI e eritromicina - ERI) e rifampicina. Todavia, casos de resistência frente a esses antimicrobianos vêm sendo reportados, especialmente à ERI. Tendo em vista a necessidade de um estudo sobre o perfil de susceptibilidade de isolados brasileiros, buscou-se verificar a concentração inibitória mínima (CIM) de AZI, CLARI e ERI frente a 44 isolados de R. equi de diferentes origens. Todos os isolados analisados demonstraram perfil de sensibilidade à AZI e CLARI; em contraste, frente à ERI, 27% (12/44) apresentaram sensibilidade intermediária. A fim de evitar falhas no tratamento da rodococcse equina, destaca-se a importância da cultura microbiológica e a realização de testes in vitro de susceptibilidade antimicrobiana de R .equi antes do início do tratamento.(AU)

Susceptibility profile of Brazilian Rhodococcus equi isolates against azithromycin, clarithromycin and erythromycin / Perfil de susceptibilidade de isolados brasileiros de Rhodococcus equi frente à azitromicina, claritromicina e eritromicina

Rhodococcus equi infection treatment is usually a macrolide (azithromycin - AZM, clarithromycin - CLR and erythromycin - ERY) and rifampicin combination. However, resistance cases have been reported, especially for ERY. In view of the need of a study about Brazilian isolates susceptibility profile, this study aimed to characterize the minimum inhibitory concentration (MIC) of the macrolides - AZM, CLR and ERY - against 44 R. equi isolates. It was found all isolates CLR and AZM sensitive; however, for ERY, 27% (12/44) were classified as intermediate sensitivity. R. equi Brazilian isolates used here showed a large susceptibility profile, except against ERY, for which it was observed some resistance evidence. In order to avoid failures in the equine rhodococcosis therapy it was highlighted the importance of microbiological culture and antimicrobial susceptibility testing in vitro before beginning treatment.

No tratamento de infecções por R. equi, usualmente emprega-se uma combinação de macrolídeos (azitromicina - AZI, claritromicina - CLARI e eritromicina - ERI) e rifampicina. Todavia, casos de resistência frente a esses antimicrobianos vêm sendo reportados, especialmente à ERI. Tendo em vista a necessidade de um estudo sobre o perfil de susceptibilidade de isolados brasileiros, buscou-se verificar a concentração inibitória mínima (CIM) de AZI, CLARI e ERI frente a 44 isolados de R. equi de diferentes origens. Todos os isolados analisados demonstraram perfil de sensibilidade à AZI e CLARI; em contraste, frente à ERI, 27% (12/44) apresentaram sensibilidade intermediária. A fim de evitar falhas no tratamento da rodococcse equina, destaca-se a importância da cultura microbiológica e a realização de testes in vitro de susceptibilidade antimicrobiana de R .equi antes do início do tratamento.

Organic extracts from Indigofera suffruticosa leaves have antimicrobial and synergic actions with erythromycin against Staphylococcus aureus.

A characteristic feature of Staphylococcus aureus is its ability to acquire resistance to antimicrobial agents. There is a need, therefore, for new approaches to combat this pathogen; for example, employing a combination of plant-derived products and antibiotics to overcome bacterial resistance. Indigofera suffruticosa is a plant popularly used to treat infections and has verified antimicrobial action. Here, we investigate the antimicrobial activity of different extracts from I. suffruticosa against S. aureus and their synergistic effects with erythromycin. Leaves of I. suffruticosa were extracted sequentially using diethyl ether, chloroform and acetone and the antimicrobial activity of each extract then tested against nine clinical isolates of S. aureus. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by microdilution tests, while the fractional inhibitory concentration (FIC) was assessed by checkerboard assay. All organic solvent extracts showed antimicrobial activity against S. aureus strains. The acetone extract was the most potent inhibitor of S. aureus (MIC and MBC of 0.78 and 3.12 mg/mL), followed by the chloroform extract (MIC and MBC of 3.12 and 6.25 mg/mL). Furthermore, acetone or chloroform extracts of I. suffruticosa enhanced the activity of erythromycin against S. aureus (FIC ≤ 0.5). We conclude that organic extracts from leaves of I. suffruticosa, alone or combined with erythromycin, are promising natural products for the development of new anti-S. aureus formulations.

Macrolide resistance in Streptococcus pneumoniae isolated from Argentinian pediatric patients suffering from acute otitis media.

Macrolide-resistant Streptococcus pneumoniae emerged in Argentina in 1995, representing 26% of invasive infection isolates in children under 5 years old. The objectives of this study were to describe the prevalence of ermB and mefA genes in macrolide-resistant S. pneumoniae isolates from acute otitis media (AOM) and to determine their genetic relatedness. Between May 2009 and August 2010, 126 S. pneumoniae isolates from 324 otherwise healthy children with a first episode of AOM were included. Twenty six of these isolates (20.6%) were resistant to erythromycin. Most frequent serotypes were: 14 (46.2%), 6A (23.1%), 19F (7.7%) and 9V (7.7%). Twenty (76.9%) carried the mefA gene, 5 (19.2%) have the ermB gene, and 1 (3.9%) both ermB + mefA. Ten clonal types were identified, mostly related to Sweden(15A)-25/ST782 (SLV63), CloneB(6A)/ST473 and England(14)-9/ ST9. This is the first study assessing the mechanisms of macrolide resistance in pneumococci isolates from pediatric AOM in Argentina and their genetic relatedness.

Prevalence of phenotypic resistance of Staphylococcus aureus isolates to macrolide, lincosamide, streptogramin B, ketolid and linezolid antibiotics in Turkey

The incidence of drug-resistant pathogens differs greatly between countries according to differences in the usage of antibiotics. The purpose of this study was to investigate the phenotypic resistance of 321 methicillin resistance Staphylococcus aureus (MRSA) and 195 methicillin susceptible S. aureus (MSSA) in a total of 516 S. aureus strains to macrolide, lincosamide, streptogramin B (MLS B), ketolid, and linezolid. Disk diffusion method was applied to determine MLS B phenotype and susceptibility to different antibiotic agents. It was found that 54.6 percent of the isolates were resistant to erythromycin (ERSA), 48 percent to clindamycin, 55 percent to azithromycin, 58.7 percent to spiramycin, 34.7 percent to telithromycin, and 0.4 percent to quinupristin-dalfopristin, respectively. No strain resistant to linezolid was found. The prevalence of constitutive (cMLS B), inducible (IMLS B), and macrolides and type B streptogramins (M/MS B) among ERSA isolates (237 MRSA, 45 MSSA) was 69.6 percent, 18.2 percent, and 12.2 percent in MRSA and 28.9 percent, 40 percent, and 31.1 percent in MSSA, respectively. In conclusions, the prevalence of cMLS B was predominant in MRSA; while in MSSA strains, iMLS B and M/MS B phenotype were more higher than cMLS B phenotype resistance. The resistance to quinupristindalfopristin was very low, and linezolid was considered as the most effective antibiotic against all S.aureus strains.

Infección diseminada por mycobacterium intracellulare en paciente VIH: reporte de un caso y revisión de la literatura / Disseminated infection due to mycobacterium intracellulare in an HIV infected patient: case report and review of the literature

La respuesta inmunitaria frente a microbacterias es de tipo celular, existiendo en pacientes VIH (+) un riesgo elevado de infecciones diseminadas. Se presenta caso de hombre de 46 años, que presenta infección por VIH de 16 años de evolución sin control. Ingresa presentando síntomas sistémicos, y desarrolla 3 adenopatías cervicales fistulizadas, adenopatía torácicas y abdominales, y masa suprarrenal izquierda. Institulo de Salud Pública confirma Mycobacterium intracellulare. Completa 1 año de tratamiento con claritromicina, etambutol y rifampicina, asintomático en controles a 2 años. Se describe diagnóstico, manejo y evolución, y se revisa historia, epidemiología, presentación y tratamiento de micobacteriosis en pacientes VIH.

The immune response to mycobacterium infection is of cellular type, existing in HIV (+) patients a higher risk of disseminated infections. We present a 46 years old male patient, that presents HIV infection of 16 years of evolution without control. He was admitted presenting systemic symptoms, and developed 3 cervical fistulized lynephadenopathies, thoracic and abdominal lymphadenopathies, and left adrenal mass. Institute of Public Health confirms Mycobacterium intracellulare. Patient completes 1 year of treatment with claritromicin, ethambutol and rifampicin, asymtomatic in controls for 2 years. We describe the diagnosis, clinical managment and evolution, and a review of the history, epidemiology, presentation and treatment of mycobacteriosis in HIV patients.

Exacerbation rate, health status and mortality in COPD--a review of potential interventions.

COPD is prevalent in Western society and its incidence is rising in the developing world. Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden. Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease. COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality. Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use. Erythromycin has been shown to decrease the rate of COPD exacerbations. Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life. Noninvasive ventilation is associated with improved quality of life. Long-term oxygen therapy improves mortality but only in hypoxic COPD patients. The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of. Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates. Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles.

Prevalence of mef and ermB genes in invasive pediatric erythromycin-resistant Streptococcus pneumoniae isolates from Argentina / Prevalencia de los genes mef y ermB en aislamientos invasivos de Streptococcus pneumoniae resistentes a eritromicina recuperados de pacientes pediátricos en Argentina

During the period 1993-2001, a total of 1,499 pneumococci isolates were recovered through the Argentinean surveillance of Streptococcus pneumoniae causing invasive disease in children under 6 years of age, 3.5% of which were erythromycin resistant. Among the 50 erythromycin-resistant strains available, 58% (n=29) harbored mefA/E genes (15 mefA, 30%; and 14 mefE, 28%), 34% (n=17) ermB, and 6% (n=3) both mefA/E plus ermB genes, while one isolate was negative for all the acquired genes studied. The England14-9 (42%), Poland6B-20 (20%) and Spain9v-3 (16%) clones were responsible for the emergence of pneumococcal macrolide resistance in pediatric population from Argentina.

En el marco del programa de vigilancia regional SIREVA, se analizaron 1499 aislamientos de Streptococcus pneumoniae causantes de enfermedad invasiva en menores de 6 años, recuperados entre 1993 y 2001. Se detectó un 3,5% de resistencia a eritromicina. De los 50 aislamientos resistentes a eritromicina que pudieron ser estudiados, el 58% (n=29) tenían los genes mefA/E (15 mefA, 30% y 14 mefE, 28%), el 34% (n=17) el gen ermB y el 6% (n=3) la combinación de genes mefA/E y ermB. Sólo un aislamiento fue negativo para todos los genes analizados. Los clones internacionales England14-9, Poland6B-20 y Spain9v-3 representaron el 78% del total de aislamientos resistentes (42, 20 y 16%, respectivamente) y se consideraron los responsables de la emergencia de la resistencia a macrólidos entre los neumococos que afectan a la población pediátrica de Argentina.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1 percent) completed the study. At the end of treatment, 95.2 percent (CI95: 88.9 percent - 100 percent) reported cure or clinical improvement; at the end of the study, that figure was 88.9 percent (CI95: 74.1 percent - 91.7 percent). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40 percent), and 8 reported presumed eradication (53.3 percent). At end of study evaluation, 9 patients showed pathogen eradication (50 percent), and 7 showed presumed eradication (38.89 percent). Therefore, negative cultures were obtained from 93.3 percent of the patients at EOT, and from 88.9 percent at the end of the study. One patient (6.67 percent of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11 percent) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3 percent of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin...