Treatment Adherence and Blood Pressure Control in Older Individuals with Hypertension

Background: Non-adherence to treatment has been identified as the main cause of uncontrolled blood pressure (BP), and may represent a greater risk in older individuals. Objective: The aim of this study was to evaluate and compare the rate of adherence to hypertension treatment using different methods, to estimate the BP control rate, and to observe if there is an association between BP control and adherence. Methods: Treatment adherence was evaluated in older patients with hypertension, followed by the public primary health care, through four methods, including the Morisky-Green test (reference), the Attitude regarding the Medication Intake questionnaire (AMI), an evaluation of adherence by the nurse in the office (Nurse Adherence Evaluation - NAE), and at home (Home Adherence Evaluation - HAE). Salt intake was estimated by 24-hour sodium urinary excretion. BP control was assessed by the awake ambulatory blood pressure monitoring. Results: Concordance between the Morisky-Green test and AMI (Kappa=0.27) or NAE (Kappa=0.05) was poor. There was a moderate concordance between the Morisky-Green test and HAE. Eighty percent had controlled BP, including 42% with white-coat effect. The group with lower salt excretion informed to avoid salt intake more times (p<0.001) and had better medication adherence (p<0.001) than the higher salt excretion group. Conclusion: The evaluated tests did not show a good concordance to the Morisky-Green test. Adherence to hypertension treatment was low; however, there was a high rate of BP control when subjects with the white-coat effect were included in the analysis. (Arq Bras Cardiol 2012;99(1):636-641)

Benefits on quality of life concomitant to metabolic improvement in intervention program for prevention of diabetes mellitus

To evaluate whether an interdisciplinary intervention program on lifestyle results in better quality of life (QoL) and lower frequencies of depression and binge eating disorder (BED) in individuals at risk for type 2 diabetes mellitus. A total of 177 individuals (32.2% men, age 55.4 +/- A 12.5 years) at risk for diabetes were allocated to a 9-month traditional (TI) or intensive interdisciplinary intervention (II) on dietary habits and physical activity including psychoeducative groups. They were submitted to questionnaires and clinical and laboratory examinations. Predictors of non-adherence were analyzed by logistic regression. Only individuals submitted to II had blood pressure and plasma glucose levels reduced. Frequencies of depression reduced in both interventions but of BED only in II (28.0-4.0%, P < 0.001). Increments in the scores of SF-36 domains (physical functioning: 11.1 +/- A 14.0 vs. 5.3 +/- A 13.0, role-emotional: 20.4 +/- A 40.2 vs. 6.2 +/- A 43.8, P = 0.05) were greater in the II than in TI, respectively. Changes in SF-36 correlated with decreases in anthropometry, blood pressure and glucose levels, depression and BED scores. Male gender was independently associated with non-adherence to the II. In addition to metabolic benefits, an interdisciplinary approach may induce desirable extrametabolic effects, favoring the control of psychiatric disorders and improving the QoL of individuals at risk for diabetes.

The impact of psychiatric diagnosis on treatment adherence and duration among victimized children and adolescents in Sao Paulo, Brazil

OBJECTIVE: Despite the high prevalence of substance abuse and mood disorders among victimized children and adolescents, few studies have investigated the association of these disorders with treatment adherence, represented by numbers of visits per month and treatment duration. We aimed to investigate the effects of substance abuse and mood disorders on treatment adherence and duration in a special programfor victimized children in Sao Paulo, Brazil. METHODS: A total of 351 participants were evaluated for psychiatric disorders and classified into one of five groups: mood disorders alone; substance abuse disorders alone; mood and substance abuse disorders; other psychiatric disorders; no psychiatric disorders. The associations between diagnostic classification and adherence to treatment and the duration of program participation were tested with logistic regression and survival analysis, respectively. RESULTS: Children with mood disorders alone had the highest rate of adherence (79.5%); those with substance abuse disorders alone had the lowest (40%); and those with both disorders had an intermediate rate of adherence (50%). Those with other psychiatric disorders and no psychiatric disorders also had high rates of adherence (75.6% and 72.9%, respectively). Living with family significantly increased adherence for children with substance abuse disorders but decreased adherence for those with no psychiatric disorders. The diagnostic correlates of duration of participation were similar to those for adherence. CONCLUSIONS: Mood and substance abuse disorders were strong predictive factors for treatment adherence and duration, albeit in opposite directions. Living with family seems to have a positive effect on treatment adherence for patients with substance abuse disorders. More effective treatment is needed for victimized substance-abusing youth.

Management of diabetes mellitus and associated cardiovascular risk factors in Brazil – the Brazilian study on the practice of diabetes care

Abstract Background The Brazilian Study on the Practice of Diabetes Care main objective was to provide an epidemiological profile of individuals with type 1 and 2 diabetes mellitus (DM) in Brazil, concerning therapy and adherence to international guidelines in the medical practice. Methods This observational, cross-sectional, multicenter study collected and analyzed data from individuals with type 1 and 2 DM attending public or private clinics in Brazil. Each investigator included the first 10 patients with type 2 DM who visited his/her office, and the first 5 patients with type 1 DM. Results A total of 1,358 patients were analyzed; 375 (27.6%) had type 1 and 983 (72.4%) had type 2 DM. Most individuals were women, Caucasian, and private health care users. High prevalence rates of hypertension, dyslipidemia and central obesity were observed, particularly in type 2 DM. Only 7.3% and 5.1% of the individuals with types 1 and 2 DM, respectively, had optimal control of blood pressure, plasma glucose and lipids. The absence of hypertension and female sex were associated with better control of type 1 DM and other cardiovascular risk factors. In type 2 DM, older age was also associated with better control. Conclusions Female sex, older age, and absence of hypertension were associated with better metabolic control. An optimal control of plasma glucose and other cardiovascular risk factors are obtained only in a minority of individuals with diabetes. Local numbers, compared to those from other countries are worse.

A study of multidrug-resistant tuberculosis in risk groups in the city of Santos, São Paulo, Brazil

Monitoring the extent of and trends in multidrug-resistant tuberculosis (MDR-TB) is a priority of the Brazilian National Tuberculosis Control Programme. The current study aimed to estimate the incidence of MDR-TB, describe the profile of TB drug resistance in risk groups and examine whether screening for MDR-TB adhered to the recommended guidelines. A descriptive study that examined diagnosed cases of pulmonary TB was conducted in the city of Santos, Brazil, between 2000-2004. Of the 2,176 pulmonary TB cases studied, 671 (30.8%) met the criteria for drug sensitivity testing and, of these cases, 31.7% (213/671) were tested. Among the tested cases, 9.4% were resistant to one anti-TB drug and 15% were MDR. MDR was observed in 11.6% of 86 new TB cases and 17.3% of 127 previously treated cases. The average annual incidence of MDR-TB was 1.9 per 100,000 inhabitants-years. The extent of known MDR-TB in the city of Santos is high, though likely to be underestimated. Our study therefore indicates an inadequate adherence to the guidelines for MDR-TB screening and suggests the necessity of alternative strategies of MDR-TB surveillance.

The impact of psychiatric diagnosis on treatment adherence and duration among victimized children and adolescents in São Paulo, Brazil

OBJECTIVE: Despite the high prevalence of substance abuse and mood disorders among victimized children and adolescents, few studies have investigated the association of these disorders with treatment adherence, represented by numbers of visits per month and treatment duration. We aimed to investigate the effects of substance abuse and mood disorders on treatment adherence and duration in a special program for victimized children in São Paulo, Brazil. METHODS: A total of 351 participants were evaluated for psychiatric disorders and classified into one of five groups: mood disorders alone; substance abuse disorders alone; mood and substance abuse disorders; other psychiatric disorders; no psychiatric disorders. The associations between diagnostic classification and adherence to treatment and the duration of program participation were tested with logistic regression and survival analysis, respectively. RESULTS: Children with mood disorders alone had the highest rate of adherence (79.5%); those with substance abuse disorders alone had the lowest (40%); and those with both disorders had an intermediate rate of adherence (50%). Those with other psychiatric disorders and no psychiatric disorders also had high rates of adherence (75.6% and 72.9%, respectively). Living with family significantly increased adherence for children with substance abuse disorders but decreased adherence for those with no psychiatric disorders. The diagnostic correlates of duration of participation were similar to those for adherence. CONCLUSIONS: Mood and substance abuse disorders were strong predictive factors for treatment adherence and duration, albeit in opposite directions. Living with family seems to have a positive effect on treatment adherence for patients with substance abuse disorders. More effective treatment is needed for victimized substance-abusing youth

Gene expression and phenotypic traits of Aggregatibacter actinomycetemcomitans in response to environmental changes

Background and Objective: Periodontopathogens experience several challenges in the oral cavity that may influence their transcription profile and resulting phenotype. This study evaluated the effect of environmental changes on phenotype and gene expression in a serotype b Aggregatibacter actinomycetemcomitans isolate. Material and Methods: Cultures in early exponential phase and at the start of stationary growth phase in microaerophilic and anaerobic atmospheres were evaluated. Cell hydrophobic properties were measured by adherence to n-hexadecane; in addition, adhesion to, and the ability to invade, KB cells was evaluated. Relative transcription of 12 virulence-associated genes was determined by real-time reverse transcritption quantitative PCR. Results: The culture conditions tested in this study were found to influence the phenotypic and genotypic traits of A. actinomycetemcomitans. Cells cultured in microaerophilic conditions were the most hydrophobic, reached the highest adhesion efficiency and showed up-regulation of omp100 (which encodes an adhesion) and pga (related to polysaccharide synthesis). Cells grown anaerobically were more invasive to epithelial cells and showed up-regulation of genes involved in host-cell invasion or apoptosis induction (such as apaH, omp29, cagE and cdtB) and in adhesion to extracellular matrix protein (emaA). Conclusion: Environmental conditions of different oral habitats may influence the expression of factors involved in the binding of A. actinomycetemcomitans to host tissues and the damage resulting thereby, and thus should be considered in in-vitro studies assessing its pathogenic potential.

Medication reconciliation and adherence: a call for clinical pharmacist

Introduction and Objectives: With the population ageing, there is a growing number of people who have several comorbidities and make use of a variety of drugs. These factors lead to a greater predisposition to adverse drug events, as well as to medication errors. The clinical pharmacist is the most indicated health professional to target these issues. The aims of this study were to analyze the profile of medication reconciliation and assess the role of the clinical pharmacist regarding medication adherence. Material and Methods: Prospective observational cohort study conducted from Jan-Mar 2013 at the Surgical Clinic of the University Hospital of the University of Sao Paulo. 117 admitted patients - over the age of 18 years, under continuous medication use and with length of hospitalization up to 120h - were included. Discrepancies were classified as intentional/unintentional and according to their risk to cause harm, and interventions were divided into accepted/not accepted. Medication adherence was measured by Morisky questionnaire. Results and Conclusions: Only 30% of hospital prescriptions showed no discrepancies between the medications that the patient was using at home and those which were being prescribed at the hospital and more than one third of those had the potential to cause moderate discomfort or clinical deterioration. One third of total discrepancies were classified as unintentional. About 90% of the interventions were accepted by the medical staff. In addition, about 63% of patients had poor adherence to drug therapy. The study revealed the importance of the medication reconciliation at patient admission, ensuring greater safety and therapeutic efficacy of the treatment during hospitalization, and orienting the patient at discharge, assuring the therapy safety.

Un’analisi statistico – economica dell’impatto delle norme WHO su nutrizione e salute

I comportamenti nutrizionali stanno assumendo sempre maggiore rilievo all’interno delle politiche comunitarie e questo sottolinea che la dieta sta avendo, negli ultimi anni, una maggiore importanza come fattore di causa e allo stesso tempo prevenzione nella diffusione di malattie croniche come il cancro, malattie cardiovascolari, diabete, osteoporosi e disturbi dentali. Numerosi studi mostrano infatti che i tassi di obesità sono triplicati nelle ultime due decadi e si è stimato che, se i livelli di obesità continueranno a crescere allo stesso tasso del 1990, nel 2010 il numero di persone obese raggiungerà i 150 milioni tra gli adulti e i 15 milioni tra bambini e adolescenti. I governi nazionali stanno quindi cercando di risolvere questo problema, a cui sono inoltre legati alti costi nazionali, tramite l’implementazione di politiche nutrizionali. Analisi di tipo cross-section sono già state evidenziate da studiosi come Schmidhuber e Traill (2006), i quali hanno effettuato un’analisi di convergenza a livello europeo per esaminare la distanza tra le calorie immesse da 426 prodotti diversi. In quest’analisi hanno così dimostrato la presenza di una similarità distinta e crescente tra i paesi europei per quanto riguarda la composizione della dieta. Srinivasan et al. invece hanno osservato la relazione esistente tra ogni singolo prodotto alimentare consumato e le norme nutrizionali dell’ Organizzazione Mondiale della Sanità (World Health Organization, WHO) Lo scopo di questa tesi è quello di evidenziare il problema a livello di aggregati nutritivi e di specifiche componenti nutrizionali come zucchero, frutta e verdura e non relativamente ad ogni singolo prodotto consumato. A questo proposito ci si è basati sulla costruzione di un indicatore (Recommendation Compliance Index) in modo da poter misurare le distanze tra la dieta media e le raccomandazioni del WHO. Lo scopo è quindi quello di riuscire a quantificare il fenomeno del peggioramento della dieta in diverse aree del mondo negli ultimi quattro decenni, tramite un’analisi panel, basandosi sui dati sui nutrienti consumati, provenienti dal database della FAO (e precisamente dal dataset Food Balance Sheets – FBS). Nella prima fase si introduce il problema dell’obesità e delle malattie croniche correlate, evidenziando dati statistici in diversi paesi europei e mondiali. Si sottolineano inoltre le diverse azioni dei governi e del WHO, tramite l’attuazione di campagne contro l’obesità e in favore di una vita più salutare e di una maggiore attività fisica. Nella seconda fase si è costruito un indicatore aggregato (Recommendation Compliance Index) in modo da analizzare le caratteristiche nella dieta dei diversi Paesi a livello mondiale rispetto alle norme del WHO. L’indicatore si basa sui dati ottenuti da FAOSTAT ed è calcolato per 149 paesi del database dell’FBS per il periodo 1961-2002. Nell’analisi si sono utilizzati i dati sulle percentuali di energia prodotta dalle varie componenti nutritive, quali grassi, grassi saturi e transaturi, zuccheri, carboidrati, proteine e le quantità di frutta e verdura consumate. Inoltre si è applicato un test statistico per testare se il valore del RCI è significativamente cambiato nel tempo, prendendo in considerazione gruppi di Paesi (Paesi OECD, Paesi in via di sviluppo e sottosviluppati). Si è voluto poi valutare la presenza o meno di un processo di convergenza, applicando l’analisi di σ-convergenza per osservare ad esempio se la variabilità è diminuita nel tempo in modo significativo. Infine si è applicato l’indicatore ad un livello micro, utilizzando il database del National Diet and Nutrition Survey, che raccoglie dati di macrocomponenti nutritive e misure antropometriche della popolazione inglese dai 16 ai 64 anni per il periodo 2000-2001. Si sono quindi effettuate analisi descrittive nonché analisi di correlazione, regressione lineare e ordinale per osservare le relazioni tra l’indicatore, i macronutrienti, il reddito e le misure antropometriche dell’ Indice di Massa Corporea (Body Mass Index, BMI) e del rapporto vita-fianchi (Waist-hip ratio, WHR).

Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

Cardiac patients after an acute event and/or with chronic heart disease deserve special attention to restore their quality of life and to maintain or improve functional capacity. They require counselling to avoid recurrence through a combination of adherence to a medication plan and adoption of a healthy lifestyle. These secondary prevention targets are included in the overall goal of cardiac rehabilitation (CR). Cardiac rehabilitation can be viewed as the clinical application of preventive care by means of a professional multi-disciplinary integrated approach for comprehensive risk reduction and global long-term care of cardiac patients. The CR approach is delivered in tandem with a flexible follow-up strategy and easy access to a specialized team. To promote implementation of cardiac prevention and rehabilitation, the CR Section of the EACPR (European Association of Cardiovascular Prevention and Rehabilitation) has recently completed a Position Paper, entitled 'Secondary prevention through cardiac rehabilitation: A condition-oriented approach'. Components of multidisciplinary CR for seven clinical presentations have been addressed. Components include patient assessment, physical activity counselling, exercise training, diet/nutritional counselling, weight control management, lipid management, blood pressure monitoring, smoking cessation, and psychosocial management. Cardiac rehabilitation services are by definition multi-factorial and comprehensive, with physical activity counselling and exercise training as central components in all rehabilitation and preventive interventions. Many of the risk factor improvements occurring in CR can be mediated through exercise training programmes. This call-for-action paper presents the key components of a CR programme: physical activity counselling and exercise training. It summarizes current evidence-based best practice for the wide range of patient presentations of interest to the general cardiology community.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantitation of synthetic cannabinoids of the aminoalkylindole type and methanandamide in serum and its application to forensic samples

After the discovery of synthetic cannabimimetic substances in 'Spice'-like herbal mixtures marketed as 'incense' or 'plant fertilizer' the active compounds have been declared as controlled substances in several European countries. As expected, a monitoring of new herbal mixtures which continue to appear on the market revealed that shortly after control measures have been taken by legal authorities, other compounds were added to existing mixtures and to new products. Several compounds of the aminoalkylindole type have been detected so far in herbal mixtures but still their consumption cannot be detected by commonly used drug-screening procedures, encouraging drug users to substitute cannabis with those products. There is a increasing demand on the part of police authorities, hospitals and psychiatrists for detection and quantification of synthetic cannabinoids in biological samples originating from psychiatric inpatients, emergency units or assessment of fitness to drive. Therefore, a liquid chromatography-tandem mass spectrometry method after liquid-liquid extraction for the quantitation of JWH-015, JWH-018, JWH-073, JWH-081, JWH 200, JWH-250, WIN 55,212-2 and methanandamide and the detection of JWH-019 and JWH-020 in human serum has been developed and fully validated according to guidelines for forensic toxicological analyses. The method was successfully applied to 101 serum samples from 80 subjects provided by hospitals, detoxification and therapy centers, forensic psychiatric centers and police authorities. Fifty-seven samples or 56.4% were found positive for at least one aminoalkylindole. JWH-019, JWH-020, JWH-200, WIN 55,212-2 and methanandamide were not detected in any of the analyzed samples.

Validation of a single item to assess daytime sleepiness for the Swiss Transplant Cohort Study

Context-Daytime sleepiness in kidney transplant recipients has emerged as a potential predictor of impaired adherence to the immunosuppressive medication regimen. Thus there is a need to assess daytime sleepiness in clinical practice and transplant registries.Objective-To evaluate the validity of a single-item measure of daytime sleepiness integrated in the Swiss Transplant Cohort Study (STCS), using the American Educational Research Association framework.Methods-Using a cross-sectional design, we enrolled a convenience sample of 926 home-dwelling kidney transplant recipients (median age, 59.69 years; 25%-75% quartile [Q25-Q75], 50.27-59.69), 63% men; median time since transplant 9.42 years (Q25-Q75, 4.93-15.85). Daytime sleepiness was assessed by using a single item from the STCS and the 8 items of the validated Epworth Sleepiness Scale. Receiver operating characteristic curve analysis was used to determine the cutoff for the STCS daytime sleepiness item against the Epworth Sleepiness Scale score.Results-Based on the receiver operating characteristic curve analysis, a score greater than 4 on the STCS daytime sleepiness item is recommended to detect daytime sleepiness. Content validity was high as all expert reviews were unanimous. Concurrent validity was moderate (Spearman ϱ, 0.531; P< .001) and convergent validity with depression and poor sleep quality although low, was significant (ϱ, 0.235; P<.001 and ϱ, 0.318, P=.002, respectively). For the group difference validity: kidney transplant recipients with moderate, severe, and extremely severe depressive symptom scores had 3.4, 4.3, and 5.9 times higher odds of having daytime sleepiness, respectively, as compared with recipients without depressive symptoms.Conclusion-The accumulated evidence provided evidence for the validity of the STCS daytime sleepiness item as a simple screening scale for daytime sleepiness.

Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program

BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART.

Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults

BACKGROUND: Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery. OBJECTIVES: To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted. SELECTION CRITERIA: Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention. DATA COLLECTION AND ANALYSIS: Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed. MAIN RESULTS: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. AUTHORS' CONCLUSIONS: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

Outer membrane porin M35 of Moraxella catarrhalis mediates susceptibility to aminopenicillins

BACKGROUND: The outer membrane protein M35 is a conserved porin of type 1 strains of the respiratory pathogen Moraxella catarrhalis. It was previously shown that M35 is involved in the uptake of essential nutrients required for bacterial growth and for nasal colonization in mice. The aim of this study was (i) to characterize the potential roles of M35 in the host-pathogen interactions considering the known multifunctionality of porins and (ii) to characterize the degree of conservation in the phylogenetic older subpopulation (type 2) of M. catarrhalis. RESULTS: Isogenic m35 mutants of the type 1 strains O35E, 300 and 415 were tested for their antimicrobial susceptibility against 15 different agents. Differences in the MIC (Minimum Inhibitory Concentration) between wild-type and mutant strains were found for eight antibiotics. For ampicillin and amoxicillin, we observed a statistically significant 2.5 to 2.9-fold MIC increase (p < 0.03) in the m35 mutants. Immunoblot analysis demonstrated that human saliva contains anti-M35 IgA. Wild-type strains and their respective m35 mutants were indistinguishable with respect to the phenotypes of autoagglutination, serum resistance, iron acquisition from human lactoferrin, adherence to and invasion of respiratory tract epithelial cells, and proinflammatory stimulation of human monocytes. DNA sequencing of m35 from the phylogenetic subpopulation type 2 strain 287 revealed 94.2% and 92.8% identity on the DNA and amino acid levels, respectively, in comparison with type 1 strains. CONCLUSION: The increase in MIC for ampicillin and amoxicillin, respectively, in the M35-deficient mutants indicates that this porin affects the outer membrane permeability for aminopenicillins in a clinically relevant manner. The presence of IgA antibodies in healthy human donors indicates that M35 is expressed in vivo and recognized as a mucosal antigen by the human host. However, immunoblot analysis of human saliva suggests the possibility of antigenic variation of immunoreactive epitopes, which warrants further analysis before M35 can be considered a potential vaccine candidate.