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Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection.

Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8-69 months and 15 carefully age-matched healthy controls once with a Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG1-4 specificity were determined by ELISA. There were no significant differences between the two groups in any single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls (P = 0.036). Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls (P = 0.005), whereas 1 month later they had significantly more IgM antibody (P = 0.038). No other significant differences were found between the groups before or after immunization with respect to antipolysaccharide Hib antibodies. Since naturally occurring IgG antibodies are thought to be acquired partly as a consequence of antigenic stimulation on mucosal surfaces, we hypothesize that the low level of specific IgG found before immunization, as well as the low total IgG in the children with RLRI, may reflect an impaired ability to prime through mucosal surfaces. This is supported by our finding of an increased IgM response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

A prediction rule for elderly primary-care patients with lower respiratory tract infections.

Prognostic scores for lower respiratory tract infections (LRTI) have been mainly derived in a hospital setting. The current authors have developed and validated a prediction rule for the prognosis of acute LRTI in elderly primary-care patients. Data including demographics, medication use, healthcare use and comorbid conditions from 3,166 episodes of patients aged > or =65 yrs visiting the general practitioner (GP) with LRTI were collected. Multiple logistic regression analysis was used to construct a predictive model. The main outcome measure was 30-day hospitalisation or death. The Second Dutch Survey of GPs was used for validation. The following were independent predictors of 30-day hospitalisation or death: increasing age; previous hospitalisation; heart failure; diabetes; use of oral glucocorticoids; previous use of antibiotics; a diagnosis of pneumonia; and exacerbation of chronic obstructive pulmonary disease. A prediction rule based on these variables showed that the outcome increased directly with increasing scores: 3, 10 and 31% for scores of <2 points, 3-6 and > or =7 points, respectively. Corresponding figures for the validation cohort were 3, 11 and 26%, respectively. This simple prediction rule can help the primary-care physician to differentiate between high- and low-risk patients. As a possible consequence, low-risk patients may be suitable for home treatment, whereas high-risk patients might be monitored more closely in a homecare or hospital setting. Future studies should assess whether information on signs and symptoms can further improve this prediction rule.

Aged↗

Pharmacokinetics and pharmacodynamics of fluoroquinolones in the respiratory tract.

Pharmacokinetic and pharmacodynamic features are important predictors of the therapeutic efficacy of an antibiotic. In respiratory tract infection, study of the clinical implication of pharmacodynamic features is complicated as infection occurs at several distinct sites. To ensure microbiological efficacy, antibiotics should not only be active against common respiratory pathogens but should also penetrate to the sites of infection. The newer fluoroquinolones combine good activity against Gram-negative and "atypical" organisms with extended Gram-positive activity, and are unaffected by penicillin susceptibility status and beta-lactamase production. Long terminal half-lives allow once-or twice-daily dosing, and a concentration in lung tissue at levels many times higher than is observed in the serum. Although the benefit of antibiotics in some lower respiratory tract infections has been questioned, they have proved effective in community-acquired pneumonia and acute exacerbations of chronic obstructive pulmonary disease. Early studies of oral fluoroquinolones versus intravenous or oral treatment with one or more agents in community-acquired pneumonia have shown promise. Although resistance is a potential problem with increased fluoroquinolone use, its rapid development is not anticipated. In conclusion, the broad-spectrum antimicrobial activity, tissue distribution and safety profile of fluoroquinolones suggest that they have a place in respiratory tract infection.

Anti-Infective Agents↗

Value of washed sputum gram stain smear and culture for management of lower respiratory tract infections in children.

To date, the technique of washed sputum examinations has not been widely used in the clinical management of lower respiratory tract infections in children. A total of 224 sputum samples from 125 pediatric patients with lower respiratory tract infections were collected for washed sputum Gram stain smears and cultures. The results with these methods were compared to find correlation rates. The value of washed sputum cultures was assessed by examining the clinical responses of the patients who received antibiotic therapies instituted on the basis of the sputum culture results. Isolation rates of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus were 22.4%, 9.4%, 4.9%, and 0.4%, respectively. For the prediction of H. influenzae, S. pneumoniae, and M. catarrhalis, the sensitivities of the washed sputum Gram stain smears compared with the culture method were 86.0%, 81.0%, and 90.9%, respectively. The specificities of the washed sputum Gram stain smear technique were 94.8%, 97.5%, and 98.1%, respectively. Overall, the sensitivity and specificity of the washed sputum Gram stain smear method were 85.5% and 87.2%, respectively. S. aureus was isolated from only one specimen; and washed sputum Gram stain smear estimation was correlated with the culture result. On the basis of the washed sputum culture results, appropriate antibiotic therapies were instituted for 93.3% of the patients with acute lower respiratory tract infections. This study suggests that the techniques of washed sputum Gram stain smear and culture are valuable and should be encouraged in clinical practice for the management of lower respiratory tract infections in children.

Bacteriological Techniques↗

Internalization of adenovirus by alveolar macrophages initiates early proinflammatory signaling during acute respiratory tract infection.

Adenovirus is a common respiratory pathogen which causes a broad range of distinct clinical syndromes and has recently received attention for its potential for in vivo gene delivery. Although adenovirus respiratory tract infection (ARTI) results in dose-dependent, local inflammation, the pathogenesis of this remains unclear. We hypothesized that alveolar macrophages (AMphi) rapidly internalize adenovirus following in vivo pulmonary administration and then initiate inflammatory signaling within the lung. To evaluate the role of AMphi in the induction of lung inflammation during ARTI in vivo, we directly assessed adenovirus uptake by murine AMphi and correlated uptake with the initiation of proinflammatory gene expression. Stimulation of cytokine (tumor necrosis factor alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and MIP-1alpha) expression in the lung was evaluated at the level of mRNA (by reverse transcription-PCR [RT-PCR]) and protein (by enzyme-linked immunosorbent assay) and by identification of cells expressing TNF-alpha and IL-6 mRNA in lung tissues (by in situ hybridization) and isolated lung lavage cells (by RT-PCR). Adenovirus, labeled with the fluorescent dye (Cy3), was rapidly and widely distributed on epithelial surfaces of airways and alveoli and was very rapidly ( approximately 1 min) localized within AMphi. At 30 min after infection AMphi but not airway epithelial or vascular endothelial cells expressed mRNA for TNF-alpha and IL-6, thus identifying AMphi as the cell source of initial cytokine signaling. IL-6, TNF-alpha, MIP-2, and MIP-1alpha levels progressively increased in bronchoalveolar lavage fluid after pulmonary adenovirus infection, and all were significantly elevated at 6 h (P < 0.05). To begin to define the molecular mechanism(s) by which adenovirus initiates the inflammatory signaling in macrophages, TNF-alpha expression from adenovirus-infected RAW264.7 macrophages was evaluated in vitro. TNF-alpha expression was readily detected in adenovirus-infected RAW cell supernatant with kinetics similar to AMphi during in vivo infection. Blockage of virus uptake at specific cellular sites, including internalization (by wortmannin), endosome acidification and/or lysis (by chloroquine) or by Ca(2+) chelation (by BAPTA) completely blocked TNF-alpha expression. In conclusion, results showed that during ARTI, (i) AMphi rapidly internalized adenovirus, (ii) expression of inflammatory mediators was initiated within AMphi and not airway epithelial or other cells, and (iii) the initiation of inflammatory signaling was linked to virion uptake by macrophages occurring at a point after vesicle acidification. These results have implications for our understanding of the role of the AMphi in the initiation of inflammation following adenovirus infection and adenovirus-mediated gene transfer to the lung.

Acute Disease↗

Immunostimulants for preventing respiratory tract infection in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are a major cause of childhood morbidity and mortality. Immunostimulants (IS) may reduce the incidence of ARTIs. OBJECTIVES: To determine the efficacy and safety of IS in preventing ARTIs in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005); MEDLINE (January 1966 to January 2006); and EMBASE (January 1990 to January 2006); PASCAL (up to January 2006); SciSearch (up to January 2006); and IPA (up to January 2006) for reports of trials. Investigators in the field were also contacted. Ongoing studies were searched in the trial registration web site, metaRegister of Controlled Trials. SELECTION CRITERIA: All comparative trials which enrolled patients less than 18 years of age were included. The intervention of interest was the use of an IS medication administered by any method for preventing ARTIs. Clinical trials using random or quasi-random allocation and comparing IS medication or medications to placebo were included. DATA COLLECTION AND ANALYSIS: The outcome on ARTIs was analyzed both as the mean number of ARTIs by group and as a percent change in the rate of ARTIs. Meta-analysis was undertaken using a random-effects model and results were presented as weighted mean differences (WMD) with 95% confidence intervals (CI). The trials search, quality assessment and data extraction were undertaken independently by two authors. A funnel plot suggested there may be publication bias in the trials identified. MAIN RESULTS: Thirty-four placebo controlled trials (3877 participants) provided data in a form suitable for inclusion in the meta-analysis. When compared with placebo, the use of IS was shown to reduce ARTIs measured as the total numbers of ARTIs (WMD -1.27; 95% CI -1.58 to -0.97) and the difference in ARTIs rates (WMD -39.68%; 95% CI -47.27% to -32.09%). The trial quality was generally poor and a high level of statistical heterogeneity was evident. The subgroup analysis of bacterial IS studies produced similar results, with lower heterogeneity. No difference in adverse events was evident between the placebo and IS groups AUTHORS' CONCLUSIONS: This review showed that IS reduces the incidence of ARTIs in children, by 40% on average. However, due to significant heterogeneity and the poor quality of the trials this positive result should be interpreted with caution. The safety profile of IS appears to be good. Further high-quality trials are needed and we encourage national health authorities to conduct large, multicenter, double-blind, placebo-controlled trials on the role of IS in the prevention of ARTIs.

Adjuvants, Immunologic↗

Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community.

BACKGROUND: Acute lower respiratory tract illness in previously well adults is usually labelled as acute bronchitis and treated with antibiotics without establishing the aetiology. Viral infection is thought to be the cause in most cases. We have investigated the incidence, aetiology, and outcome of this condition. METHODS: Previously well adults from a stable suburban population consulting over one year with a lower respiratory tract illness were studied. For the first six months detailed investigations identified predetermined direct and indirect markers of infection. Evidence of infection was assessed in relation to presenting clinical features, indirect markers of infection, antibiotic use, and outcome. RESULTS: Consultations were very common, particularly in younger women (70/1000 per year in previously well women aged 16-39 years), mainly in the winter months; 638 patients consulted, of whom 316 were investigated. Pathogens were identified in 173 (55%) cases: bacteria in 82 (Streptococcus pneumoniae 54, Haemophilus influenzae 31, Moraxella catarrhalis 7), atypical organisms in 75 (Chlamydia pneumoniae 55, Mycoplasma pneumoniae 23), and viruses in 61 (influenza 23). Seventy nine (24%) had indirect evidence of infection. Bacterial and atypical infection correlated with changes in the chest radiograph and high levels of C reactive protein but not with (a) the GP's clinical assessment of whether infection was present, (b) clinical features other than focal chest signs, and (c) outcome, whether or not appropriate antibiotics were prescribed. CONCLUSIONS: Over 50% of patients have direct and/or indirect evidence of infection, most commonly bacterial and atypical pathogens, but the outcome is unrelated to the identified pathogens. Many patients improve without antibiotics and investigations do not help in the management of these patients. GPs can reassure patients of the causes and usual outcome of this self-limiting condition.

Acute Disease↗

Pathogenic significance of Klebsiella oxytoca in acute respiratory tract infection.

A retrospective study of all Klebsiella isolations from patients admitted to hospital with acute respiratory tract infections over a 27-month period was carried out. Ten of the Klebsiella isolations from sputum and one from a blood culture were identified as Klebsiella oxytoca. The clinical and radiological features of six patients are described. Four of these patients had lobar pneumonia, one bronchopneumonia, and one acute respiratory tract infection superimposed on cryptogenic fibrosing alveolitis. One of the patients with lobar pneumonia had a small-cell carcinoma of the bronchus. We concluded that Klebsiella oxytoca was of definite pathogenic significance in these six patients and of uncertain significance in the remaining five patients. Klebsiella oxytoca has not previously been described as a specific pathogen in the respiratory tract. Close co-operation between clinicians and microbiologists in the management of patients with respiratory infections associated with the Enterobacteriaceae is desirable.

Acute Disease↗

Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection.

BACKGROUND: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of wheezing following RSV LRTI in children up to the age of 3 years. METHODS: A prospective cohort study was performed in 140 hospitalised infants with RSV LRTI. Continuous follow up data were obtained with a unique log in which parents noted daily respiratory symptoms. RESULTS: A marked decrease in wheezing was seen during the first year of follow up. The burden of wheezing following RSV LRTI was observed during the winter season. Signs of airflow limitation during RSV LRTI were strongly associated with wheezing during the follow up period. Total and specific serum immunoglobulin E levels, patient eczema, and parental history of atopy were not associated with wheezing. CONCLUSIONS: Airway morbidity following RSV LRTI has a seasonal pattern, which suggests that viral upper respiratory tract infections are the predominant trigger for wheezing following RSV LRTI. There is a significant decrease in airway symptoms during the first 12 months after admission to hospital. Simple clinical variables, but not allergic risk factors, can predict the development of wheezing following RSV LRTI.

Child, Preschool↗

Circulating levels of pro-atrial natriuretic peptide in lower respiratory tract infections.

OBJECTIVE: To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome. DESIGN: Prospective observational study. Setting. Emergency department of a university hospital. SUBJECTS: A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay. RESULTS: MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07). CONCLUSIONS: MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Acute Disease↗

[Basic study of peptide histidine isoleucine (PHI) immunoreactivity in the rat respiratory tract].

Peptide histidine isoleucine (PHI) as well as vasoactive intestinal peptide (VIP) is considered to be a neurotransmitter of non-adrenergic and non-cholinergic inhibitory nerves in the respiratory tract. We tried to measure PHI immunoreactivity in rat respiratory tracts to evaluate the movement of PHI. A high titer of PHI antiserum which did not react with VIP was obtained from a rabbit immunized with rat PHI, and rat PHI radioimmunoassay was established with this antiserum. Tracheas, extrapulmonary bronchi and lungs were dissected from rats sacrificed by microwave irradiation. They were homogenized with 0.5 N acetic acid and centrifuged at 35,000 X g. Lyophilized supernates were used as samples for the radioimmunoassay. PHI immunoreactivity per g wet weight tissue was 5.12 +/- 1.35 (mean +/- SD) pmol in the tracheas, 1.66 +/- 1.15 pmol in the extrapulmonary bronchi and 0.12 +/- 0.06 pmol in the lungs. PHI immunoreactivity occurred more in the central airways than in the peripheral ones. VIP immunoreactivity in rat respiratory tracts, assayed simultaneously by radioimmunoassay using commercialized VIP antiserum, was as strong as the of PHI, suggesting that PHI and VIP may be produced from the same precursor at the ratio of 1:1 in rat respiratory tracts.

Animals↗

New features in the development of the submucosal gland of the respiratory tract.

The development of submucosal glands in the respiratory tract was studied by light and scanning electron microscopy in the rat, fetal dog and fetal sheep. From the results obtained the present concepts about the formation of these glands in man were questioned and an alternative hypothesis proposed. With scanning electron microscopy the development of the submucosal gland was seen to begin with an aggregation of low electron-responsive cells. Within such an aggregate, a pit, several microns in diameter, was formed. This pit was usually surrounded by medium electron-responsive cells possessing primary cilia in the rat, and by low electron-responsive cells in the fetal dog. In the rat medium electron-responsive cells appeared in other areas of the aggregate, preceded by apical elevations on the low electron-responsive cells. Further development in the rat led to a disappearance of the low electron-responsive cells, differentiation of ciliated and brush cells, and enlargement of the gland orifice. With light microscopy it was observed that the initial gland buds in both the rat and fetal sheep contained lumina several microns in size. These have not been reported by previous investigators. The bud extended into the underlying tissue and developed many simple tubules. The lumina of these tubules were consistently larger than the channel close to the epithelial surface. The cells of these tubules were also the first to differentiate into mucous and serous cells. The development of glands in the rat, in contrast to the sheep, began after birth. In the sheep, unlike the rat, the lumina of the developing glands were often filled with acidic mucosubstances, even though the cells of these glands did not stain for such material. Hence it is suggested that this material is derived from the mucin-containing cells of the surface epithelium and is carried into the interior of the developing gland by the fluid present in the respiratory tract during intrauterine life.

Animals↗

Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy.

Acute respiratory infections represent a significant cause of over-prescription of antibiotics and are one of the major reasons for absence from work. The leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used as a medicinal herb in the treatment of infectious diseases. Systematic literature searches were conducted in six computerised databases and the reference lists of all papers located were checked for further relevant publications. Information was also requested from manufacturers, the spontaneous reporting schemes of the World Health Organisation and national drug safety bodies. No language restrictions were imposed. Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Adverse events reported following administration of A. paniculata were generally mild and infrequent. There were few spontaneous reports of adverse events. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.

Andrographis↗

Broncho-alveolar lavage in chronic upper respiratory tract infections.

The relationship between upper and lower respiratory tract infections has been demonstrated previously, although the effect of chronic infection of one tract on the other has not been well studied. This work analyses the broncho-alveolar lavage fluid of patients with chronic purulent rhino-sinusitis and reveals an increase in total and neutrophil cell counts as well as an increase in immuno-globulin A levels. The associated increase in the neutrophil nitro-blue tetrazolium dye reduction test positivity provides evidence for increased phagocytosis to compensate for the increased contamination of the lower respiratory tract.

Adolescent↗

Virus infections of the respiratory tract cytopathologic and clinical analysis.

Thirty-three cases of respiratory tract virus infections diagnosed cytologically are reviewed. The clinical and demographic data are presented and correlated with an analysis of the cytologic findings. Herpes virus was the most common infection. It occurred in patients with other severe medical problems and had little apparent effect on the clinical outcome of any particular case. Quantitative and qualitative cytologic findings did not correlate with the severity of the herpetic infection. The virus was isolated in culture in only one of 21 cases of Herpes virus infection. Cases in the later part of the study indicate an increasing incidence or recognition of the infection in the respiratory tract. In this series there was a clustering of Herpes virus cases in relation to date of admission and hospitalization in respiratory intensive care. Cytomegalovirus infection was recognized in four cases. This infection occurs in the immune suppressed patient and can be made reliably from cytologic findings. Smears must be screened thoroughly and carefully as the characteristic inclusion is seen in only a rare cell. Bronchial brushing specimens are the most useful. The disease should not be fatal if the level of immune suppression can be manipulated and the patients basic medical problem is not too severe. Cytologic findings contribute little information to tjor medical problems and the adenovirus infection was incidental. Thy cytologic findings in some cases may be non-specific since antibody studies and culteral confirmation are lacking in these cases.

Adenoviridae Infections↗

The incidence of Legionella pneumophila as the cause of acute ambulatory lower respiratory tract infection.

Seventy-nine ambulatory patients with acute lower respiratory tract infection were evaluated for Legionella pneumophila by acute and convalescent antibody titers. None of the patients met the traditional criteria for the diagnosis of acute infection caused by Legionella pneumophila. Currently accepted criteria for diagnosing legionellosis by serologic means may or may not be applicable to mild respiratory tract infections.

Ambulatory Care Facilities↗

Activity of oral beta-lactam antimicrobial agents versus respiratory tract isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the era of antibiotic resistance.

The management of outpatient respiratory tract infections with oral beta-lactam antimicrobial agents has been complicated by the emergence of beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis and isolates of Streptococcus pneumoniae that express varying levels of beta-lactam resistance because of altered penicillin-binding proteins. There is no question that all 3 of these important respiratory tract pathogens have changed conspicuously in the context of decreased activity of beta-lactam antimicrobial agents. The question arises, what does this change mean from a clinical perspective? In this review, the in vitro activity of various oral beta-lactam antimicrobial agents versus contemporary isolates of H influenzae, M catarrhalis, and S pneumoniae will be compared. The approach that is used in defining organisms as being susceptible or resistant to beta-lactam antimicrobial agents will be elucidated. Finally, an effort will be made to assess the ramifications of beta-lactam resistance for therapeutic efficacy in patients with respiratory tract infections caused by these 3 bacteria. We conclude that, notwithstanding diminished beta-lactam activity for many clinical isolates of H influenzae, M catarrhalis, and S pneumoniae, certain agents remain effective in treating outpatient respiratory tract infections.

Administration, Oral↗

The use of macrolides in treatment of upper respiratory tract infections.

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to beta-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to beta-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in both S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found to be responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species, producing an efflux pump (mef), and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.

Anti-Bacterial Agents↗