Effect Of Antimicrobial Therapy Research Articles

Critically important antimicrobial preparations for veterinary medicine

The resistance of microorganisms, bacterial pathogens, to antimicrobials is a global problem in both healthcare and veterinary medicine. It is believed that the main reason for the emergence and spread of antimicrobial resistance in humans is the transfer of antibiotic resistant strains of microorganisms or genes, determinants of resistance, through products of animal origin from productive animals to humans. Thus, the main way of antimicrobial resistance containment is to restrain and minimize it through the prudent use of antibiotics in veterinary medicine, especially those that are critically important for productive animals. In addition, some classes of antibacterial substances and antibiotics, that are widely used in humane medicine, are used in veterinary medicine. The need to use and preserve these important therapeutic agents is relevant from the point of view of the concept «One Health». The article provides a list of all antibacterial substances used by productive animals for their importance in veterinary medicine, developed by a special group of experts of the World Organisation for Animal Health (OIE). Any antimicrobial agent authorized for use in veterinary medicine for productive animals, in accordance with the criteria for quality, safety and efficacy as defined in Section 6.9 of the Terrestrial Animal Health Code, is considered to be important for veterinary medicine. All the antimicrobial substances used for productive animals are divided in this list on critical, very important and important for veterinary medicine. Attention was also drawn to the peculiarities of the use of critical antimicrobial agents in veterinary medicine, especially those recognized as critical in humane medicine. These include aminoglycosides, cephalosporins of the 3rd and 4th generation, fluoroquinolones, glycopeptides, macrolides, some penicillins and polymyxins. The article also describes the classification of critical antimicrobials by the European Medicines Agency (EMA) and the Panel of Experts on Antimicrobials (AMEG) of the WHO based on the risk profile for humans through the development of antimicrobial resistance after application to productive animals. Such an assessment will give veterinary practitioners an important justification when they make decisions about the clinical treatment of bacterial infections and the responsible appointment of antimicrobial therapy. This will help to reach the balance among the achievement of the effectiveness of antimicrobial therapy of productive animals, reducing of the selective pressure on the development of antibiotic resistance and ensuring of a high level of human health.

A New Concept of Enhancing the Efficacy of Antimicrobial Therapy of Pyo-Inflammatory Diseases in Children

Pyo-inflammatory diseases are quite common among various surgical diseases in children. Etiotropic antimicrobial therapy of these conditions is of primary importance. Modern pathogenic bacteria possess a high degree of drug resistance to antimicrobials, which significantly reduces the effectiveness of treatment and contributes to the spread of infection and the development of pyo-inflammatory complications.The objective of the research was to study peculiar properties of virulence factors production by S. aureus within 24 hours as well as to determine on this basis the directions of improving the efficiency of antimicrobial therapy of pyo-inflammatory diseases in children.Materials and methods. There were conducted in vitro experimental microbiological studies concerning the study of the daily dynamics of virulence factors of causative agents of purulent-inflammatory diseases in children. The materials for the study were as follows: wound tissues, purulent exudate, dressings and suture material, catheters and drainage elements.Results. Microbiological studies revealed that drug resistance of pathogenic microorganisms originates from the production of various factors of bacterial aggression including the formation of biofilms. The study showed that the level of production of virulence factors and the sensitivity of S. aureus to antimicrobial agents were not constant over the day. Recorded peaks of increasing adhesive activity, teichoic acids content, production of planktonic cells and formation of dense biofilms by S. aureus depended on the time of administration of antimicrobials and maximum concentration of the medication in an organism.Conclusions. The regularity observed allowed us to develop a new concept to increase the efficiency of treatment of pyo-inflammatory diseases in children by means of change in the time for administration of antimicrobial agents during the day so that the period of maximum action would coincide with periods of minimal drug resistance of pathogens. This will allow us to significantly improve the effectiveness of antimicrobial therapy without increasing doses of medications that are administered.

WS02.8 Altered therapeutic susceptibility of mucoid Pseudomonas aeruginosa in artificial sputum medium

Objectives The relevance of antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients has recently come into question as the traditional in vitro test conditions used have little in common with the in vivo environment. To improve our understanding of mucoid P. aeruginosa infection in the CF lung, an artificial sputum medium (AS) was used to mimic the nutritional environment in CF sputum. OligoG, a low molecular weight alginate oligomer, is a novel therapeutic that has been shown to disrupt pseudomonal biofilms and potentiate antibiotic effects. Its therapeutic effect in an environment mimicking the lung however has not previously been tested. Methods Growth curves and susceptibility testing of colistin +/– OligoG of the CF clinical isolate Pseudomonas aeruginosa NH53788A were compared in Mueller-Hinton broth (MH) and AS. Anti-biofilm effects were visualised using LIVE/DEAD® confocal laser scanning microscopy (CLSM) and scanning electron microscopy. Results CLSM confirmed the dose-dependent biofilm disruption properties of OligoG, with an enhanced combined antimicrobial effect observed when tested in conjunction with colistin, characterised by cellular aggregation and decreased bacterial viability in MH. Growth in AS was considerably lower compared to MH, with minimum inhibitory concentrations (MICs) for colistin increased 4-fold (0.4 compared to 0.1 mg/L in MH). A dose dependent reduction in biofilm microcolony size was also seen when treated with OligoG in AS. Conclusion The contrasting results obtained in the individual medium reflect the role of local environment on the effectiveness of antimicrobial therapy.

Sepsis in standard care: patients' characteristics, effectiveness of antimicrobial therapy and patient outcome--a cohort study.

Fast diagnosis and initiation of appropriate antibiotic therapy is pivotal for the survival of sepsis patients. However, most studies on suspected sepsis patients are conducted in the intensive care unit or in the emergency room setting, neglecting the standard care setting. This study evaluated sepsis risk factors, microbiological accurateness of the initial empiric antimicrobial therapy and its effect on hospital mortality in standard care patients. In this prospective observational cohort study, patients with clinically suspected sepsis meeting two or more SIRS criteria were screened on standard care wards. After hospital discharge, occurrence of an infection was assessed according to standardized criteria, and empirical antibiotic therapy was evaluated using antibiograms of recognized pathogens by expert review. Of the 2384 screened patients, 298 fulfilled two or more SIRS criteria. Among these were 28.2 % SIRS patients without infection, 46.3 % non-bacteremic/fungemic sepsis patients and 25.5 % bacteremic/fungemic sepsis patients. Occurrence of a malignant disease and chills were associated with a higher risk of patients having bacteremic/fungemic sepsis, whereas other described risk factors remained insignificant. In total, 91.1 % of suspected sepsis patients received empirical antimicrobial therapy, but 41.1 % of bacteremic sepsis patients received inappropriate therapy. Non-surviving bacteremic sepsis patients received a higher proportion of inappropriate therapy than those who survived (p = 0.022). A significant proportion of bacteremic sepsis patients receive inappropriate empiric antimicrobial therapy. Our results indicate that rapid availability of microbiological results is vital, since inappropriate antimicrobial therapy tended to increase the hospital mortality of sepsis patients.

The Dilemma of Antimicrobial Treatment of Shiga Toxin-producing Escherichia coli

The Dilemma of Antimicrobial Treatment of Shiga Toxin-producing Escherichia coli

Ceftaroline and gentamicin for the treatment of daptomycin‐non‐susceptible meticillin‐resistant Staphylococcus aureus bacteraemia and endocarditis in a pregnant patient

Introduction: Vancomycin remains the mainstay in the treatment of meticillin‐resistant Staphylococcus aureus (MRSA) bacteraemia; however, concerns exist about its continued efficacy in the presence of rising MICs. Daptomycin serves as an alternative but has also witnessed increases in reduced susceptibility. Several published case reports have demonstrated the potential utility of ceftaroline as a viable therapeutic option for invasive MRSA infections, including endocarditis. Case presentation: A 23‐year‐old pregnant female presented with complaints of foot pain and fevers up to 104 °F. Her past medical history included polysubstance abuse, hepatitis C, intravenous drug use and a right arm abscess 2 years ago due to MRSA. Daptomycin was started empirically due to an allergy (angioedema) to vancomycin. Blood cultures returned positive for MRSA and remained persistently positive for 10 days at which point ceftaroline was added. Subsequent positive blood cultures on day 12 revealed daptomycin‐non‐susceptible MRSA at an MIC of 4 µg ml–1. Consequently, daptomycin was discontinued and gentamicin was added. Blood cultures were negative by day 14 and the patient completed a total of 2 weeks of gentamicin and 4 weeks of ceftaroline after the first negative blood culture. The baby was born premature at 34 weeks and 2 days due to complications of pregnancy; however, no adverse effects of antimicrobial therapy were noted. Conclusion: We describe the emergence of daptomycin‐non‐susceptibility during treatment and the successful eradication of persistent daptomycin‐non‐susceptible MRSA bacteraemia and endocarditis with a combination of ceftaroline and gentamicin in a pregnant female.

Atypical pneumonia

We present the key advances in the infections that clinicians conventionally associate with atypical pneumonia: legionellosis, Mycoplasma pneumonia, Chlamydophila species pneumonia and Q fever. There have been significant developments in molecular diagnosis to include Mycoplasma pneumoniae and Chlamydophila pneumoniae in multiplex PCR of respiratory specimens. There are diagnostic challenges in distinguishing carriage from infection, which is recognized in C. pneumoniae and now also evident in M. pneumoniae. Macrolide-resistant M. pneumoniae has emerged in Asia. There are new antimicrobials on the horizon in the ketolide class with activity against typical and atypical pathogens and useful empirical agents. There are few advances in our knowledge of the epidemiology of atypical pathogens or the effectiveness of antimicrobial therapy--empirical or pathogen specific. However, if molecular testing becomes widely implemented, there will be an increased understanding of the epidemiology and presentation of atypical pneumonia and a shift to more targeted antimicrobial therapy.

Treating Skin Infections

Given the detrimental effects of antimicrobial therapy both in promoting antibiotic resistance and in altering the microbiome, shortening the duration

Nitrate reductase activity of bacteria in saliva of term and preterm infants

The salivary glands of adults concentrate nitrate from plasma into saliva where it is converted to nitrite by bacterial nitrate reductases. Nitrite can play a beneficial role in adult gastrointestinal and cardiovascular physiology. When nitrite is swallowed, some of it is converted to nitric oxide (NO) in the stomach and may then exert protective effects in the gastrointestinal tract and throughout the body. It has yet to be determined either when newborn infants acquire oral nitrate reducing bacteria or what the effects of antimicrobial therapy or premature birth may be on the bacterial processing of nitrate to nitrite. We measured nitrate and nitrite levels in the saliva of adults and both preterm and term human infants in the early weeks of life. We also measured oral bacterial reductase activity in the saliva of both infants and adults, and characterized the species of nitrate reducing bacteria present. Oral bacterial conversion of nitrate to nitrite in infants was either undetectable or markedly lower than the conversion rates of adults. No measurable reductase activity was found in infants within the first two weeks of life, despite the presence of oral nitrate reducing bacteria such as Actinomyces odontolyticus, Veillonella atypica, and Rothia mucilaginosa. We conclude that relatively little nitrite reaches the infant gastrointestinal tract due to the lack of oral bacterial nitrate reductase activity. Given the importance of the nitrate-nitrite-NO axis in adults, the lack of oral nitrate-reducing bacteria in infants may be relevant to the vulnerability of newborns to hypoxic stress and gastrointestinal tract pathologies.

The airway microbiome in cystic fibrosis and implications for treatment

Lung disease in cystic fibrosis (CF) results from chronic airway infection and inflammation leading to progressive bronchiectasis and respiratory failure. Bacterial pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia, are known contributors. Recent studies using culture-independent molecular techniques and anaerobic cultures have broadened our view of CF airway bacterial communities. Sanger sequencing, high-throughput pyrosequencing, and phylogenetic microarray analysis have been used to comprehensively examine the airway microbiome in CF. Findings confirm that CF airway bacterial communities are highly complex structures with anaerobes frequently present. Importantly, there is evidence that loss of community diversity and richness is associated with older age and decreased lung function in CF. Bacterial communities are also likely influenced by antibiotic use, chronic P. aeruginosa infection, host genetic background (ΔF508 CFTR mutation) and geographic variations. Quantitative anaerobic cultures also detect high quantities of anaerobes from CF airway samples, including during pulmonary exacerbations. The effect of antimicrobial therapy on the airway microbiome needs further investigation. In addition, probiotic approaches have been recently studied; whether probiotics act by altering microbial communities or by modulating host inflammatory response is unknown. Complex bacterial communities, including traditional CF-associated pathogens and anaerobic bacteria, are common in CF airways. Novel therapeutic approaches aimed at modulating airway bacterial communities may lead to improved treatment of CF lung disease.

Resistência antimicrobiana associada em isolados clínicos de Enterococcus spp

The increasing prevalence of enterococci strains in hospitals, particularly among isolates of vancomycin-resistant enterococci (VRE), poses important problems because of the limited effect of antimicrobial therapy for enterococcal infections. This work presents a retrospective investigation of quantitative in vitro susceptibility data for the range of antimicrobials against Enterococcus spp. isolates and evaluation of the association of resistance between antimicrobial agents recommended as the treatment of choice for infections caused by VRE through calculation of the relative risk. Of the 156 enterococci isolates, 40 (25.6%) were resistant to 3 or more antimicrobials, including 7.7% (n = 12/156) vancomycin resistant. The association of elevated resistance was more pronounced among VRE isolates against alternative and primary antimicrobials for the treatment of infections caused by these pathogens, including ampicillin (100%, RR = 7.2), streptomycin (90.9%, RR = 4.9), rifampin (91.7%, RR = 3.1) and linezolid (50%, RR = 11.5), despite high susceptibility to this drug (94.9%). The significant associated resistance to alternative and first choice antimicrobials used in the treatment of serious infections of strains with the VRE phenotype and that require a combined therapeutic regime, revealed even more limited therapeutic alternatives in the institution analyzed.

The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women

Bacterial vaginosis (BV) is a very common cause of vaginitis that has been associated with a high incidence of obstetric and gynaecologic complications and increased risk of HIV-1 transmission. This has led to renewed research interest in its treatment. To assess the effects of antimicrobial agents on BV in non-pregnant women. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, and African Healthline (December 2007); and proceedings of relevant international conferences (from 1981 to date). Randomised controlled trials comparing any two or more antimicrobial agents, or antimicrobial agents with placebo or no treatment, in women with clinical or Gram-stain criteria of BV. Two authors independently assessed trial quality and extracted data from the original publications while the third author cross checked the data. Twenty-four trials involving 4422 participants were reviewed. Most examined symptomatic women only. Only seven trials analysed results by intention to treat; we re-analysed the remainder.Compared with placebo, clindamycin showed a lower rate of treatment failure (relative risk (RR) 0.25, 95% confidence interval (CI) 0.16 to 0.37). Clindamycin and metronidazole showed identical rates of treatment failure, irrespective of regimen type, at two and four-week follow up (RR 1.01, 95% CI 0.69 to 1.46; RR 0.91, 95% CI 0.70 to 1.18, respectively). Clindamycin tended to cause a lower rate of adverse events (RR 0.75, 95% CI 0.56 to 1.02); metallic taste, and nausea and vomiting were more common in the metronidazole group (RR 0.08, 95% CI 0.1 to 0.59; RR 0.23, 95% CI 0.10 to 0.51, respectively). Given intravaginally as gelatin tablets, lactobacillus was more effective than oral metronidazole (RR 0.20, 95% CI 0.05 to 0.08). Similarly, oral lactobacillus combined with metronidazole was more effective than metronidazole alone (RR 0.33, 95% CI 0.14 to 0.77). Clindamycin showed a lower rate of clinical failure than triple sulfonamide cream (RR 0.46, 95% CI 0.29 to 0.72). Hydrogen peroxide douche showed a higher rate of clinical failure (RR 1.75, 95% CI 1.02 to 3.00) and adverse events (RR 2.33, 95% CI 1.21 to 4.52) than a single 2 g dose of metronidazole. Clindamycin preparations, oral metronidazole, and oral and intravaginal tablets of lactobacillus were effective for bacterial vaginosis. Hydrogen peroxide douche and triple sulphonamide cream were ineffective. Metronidazole caused metallic taste, nausea and vomiting. We need better-designed trials with larger sample sizes to test the effectiveness of promising drugs.

A 62-month retrospective epidemiological survey of anaerobic bacteraemia in a university hospital

The incidence of anaerobic bacteraemia was studied retrospectively over 62 months at Mont-Godinne University Hospital, Yvoir, Belgium. The distribution of organisms, clinical presentations, choice of antimicrobial therapy and clinical outcome were analysed. The proportion of positive blood cultures yielding obligate anaerobes was 3.3%. The overall incidence of clinically significant anaerobic bacteraemia was 0.51 cases/1,000 patient admissions (0.61 cases/10,000 hospital-days), but was significantly higher in patients with active haematological malignancies than in other groups (5.97/10,000 vs. 0.33/10,000 hospital-days; p < 0.05). The Bacteroides fragilis group accounted for 61% of isolates, followed by Clostridium spp. (12.2%), Peptostreptococcus spp. and Leptotrichia spp. (7.3% each) and Fusobacterium spp. (4.8%). The most common risk-factors were gastrointestinal surgery (49%) and active haematological malignancies with chemotherapy and/or bone marrow graft (47%). One or more co-morbidities were present in 30 (77%) of 39 patients. The lower gastrointestinal tract (41%) and the oropharynx (23%) were the two most frequent presumed or proven sources for bacteraemia, with the origin remaining unknown in eight (20.5%) cases. The overall mortality rate (evaluated 7 days after the occurrence of bacteraemia) was 13%. Fatal outcome correlated with the severity of underlying diseases and the immunosuppressed status of the patients rather than with the causative pathogen or the effectiveness of antimicrobial therapy. Likewise, there was no difference in the mortality rate between patients with monomicrobial and polymicrobial bacteraemia. Overall, the data re-emphasise the importance of anaerobic bacteraemia, especially in patients with haematological malignancies.

Low Risk of Hemolytic Uremic Syndrome after Early Effective Antimicrobial Therapy for Shigella dysenteriae Type 1 Infection in Bangladesh

Hemolytic uremic syndrome (HUS) may complicate up to 15% of cases of Shiga toxin (Stx)-expressing enterohemorrhagic Escherichia coli (STEC) O157:H7 infections in children. Administration of antimicrobials has been reported to increase the risk of STEC-associated HUS by >10-fold, presumably by increasing the expression and release of Stx by dying STEC bacteria. Shigella dysenteriae type 1 also expresses Stx. However, the effect of antimicrobial therapy on Stx release and the risk of HUS in humans is unknown. We measured serial stool Stx concentrations before and after administration of antimicrobials in 20 children infected with S. dysenteriae type 1 who had frank dysentery of <72 h duration. We also reviewed the results of 7 shigellosis drug trials performed in Bangladesh during 1988-2000 to estimate the risk of HUS. In these studies, antimicrobials were administered within 96 h after the onset of dysentery. Stx levels decreased in stool samples obtained from 17 of 20 children after administration of antimicrobial agents; none of the 20 children developed HUS. Of 378 individuals infected with S. dysenteriae type 1 who were enrolled in drug trials (128 adult men [age, 18-60 years] and 250 children [age, 6 months to 15 years]), 351 (93%) received an antimicrobial agent to which the S. dysenteriae organism was susceptible <or=96 h after the onset of symptoms; HUS developed in 1 child. The risk of developing HUS was 0.0026 for all participants (95% confidence interval, <0.001 to 0.015) and was 0.004 for children (95% confidence interval, 0.001-0.022). In persons infected with S. dysenteriae type 1, early administration of effective antibiotics is associated with decreased Stx concentrations in stool and a low risk of developing HUS.

Effect of Antimicrobial Therapy with Amoxicillin and Cefprozil on Bacterial Interference and Beta-Lactamase Production in the Adenoids

To compare the effects on the bacterial flora of the adenoids of antimicrobial therapy with amoxicillin or cefprozil, we enrolled in a prospective randomized study 60 children scheduled for elective adenoidectomy because of recurrent otitis media. They were randomized before surgery into 3 groups of 20 patients each: a no-therapy group, and groups with 10 days of either amoxicillin or cefprozil therapy. Core adenoid materials were quantitatively cultured for aerobic and facultative bacteria. The in vitro ability of alpha-hemolytic streptococci (AHS) to inhibit the growth of non-type B Haemophilus influenzae and Streptococcus pneumoniae was determined. The number of organisms in adenoids obtained from patients treated with either antibiotic was reduced as compared to that in adenoids from controls. However, in patients treated with amoxicillin, a significant decline in the number of AHS, and an increase (in Staphylococcus aureus) or no change in the number of other beta-lactamase-producing bacteria (BLPB) was noted. In contrast, in those treated with cefprozil, no change was noted in the frequency of recovery of AHS, and the number of BLPB decreased. Interfering AHS were more often recovered in patients treated with cefprozil. We conclude that the adenoids contain more interfering AHS after therapy with a second-generation oral cephalosporin (cefprozil) than after amoxicillin therapy. This study suggests a potential beneficial effect of using an antimicrobial that selectively spares interfering AHS while inhibiting BLPB.

Histologic endometritis in asymptomatic human immunodeficiency virus–infected women: characterization and effect of antimicrobial therapy

Objective To estimate the prevalence, risk factors, clinical symptoms and signs, and response to antimicrobial therapy of histologic endometritis in human immunodeficiency virus (HIV)-infected women without clinical salpingitis. Methods This was a cross-sectional study of 42 HIV-infected women enrolled from a single clinic. Subjects underwent standardized history, examination, and laboratory determinations, including endometrial biopsy. Women with suspected pelvic inflammatory disease were excluded. All women were given antibiotics and repeat evaluation in 5–7 weeks. Histologic endometritis was defined by at least one stromal plasma cell per 120× field and five or more surface polymorphonuclear leukocytes per 400× field. Chi-square and Fisher exact tests were used as appropriate. Results Histologic endometritis was present among 16 (38%) of 42 evaluable HIV-infected women, none of whom had Chlamydia trachomatis or Neisseria gonorrhoeae. Douching three or more times per month, history of ectopic pregnancy, and two or more prior urinary tract infections were associated with endometritis, as was elevated erythrocyte sedimentation rate ( P ≤ .05). Physical examination findings and mean CD4+ lymphocyte count were similar among those with and without endometritis. In the nine HIV-infected women with a repeat biopsy, endometritis decreased from four (44%) to two (22%) after treatment ( P = .30). Conclusion The prevalence of histologic endometritis in HIV-infected women was high despite few examination findings and no demonstrated pathogens. Endometritis in HIV-infected women might be related to pathogens not evaluated, to prior infection, or to reduced immunity from HIV.

225 Prognostic value of KIT mutation in localized gastrointestinal stromal tumors (GIST)

The incidence of anaerobic bacteraemia was studied retrospectively over 62 months at Mont-Godinne University Hospital, Yvoir, Belgium. The distribution of organisms, clinical presentations, choice of antimicrobial therapy and clinical outcome were analysed. The proportion of positive blood cultures yielding obligate anaerobes was 3.3%. The overall incidence of clinically significant anaerobic bacteraemia was 0.51 cases/1000 patient admissions (0.61 cases/10 000 hospital-days), but was significantly higher in patients with active haematological malignancies than in other groups (5.97/10 000 vs. 0.33/10 000 hospital-days; p < 0.05). The Bacteroides fragilis group accounted for 61% of isolates, followed by Clostridium spp. (12.2%), Peptostreptococcus spp. and Leptotrichia spp. (7.3% each) and Fusobacterium spp. (4.8%). The most common risk-factors were gastrointestinal surgery (49%) and activehaematological malignancies with chemotherapy and/or bone marrow graft (47%). One or more co-morbidities were present in 30 (77%) of 39 patients. The lower gastrointestinal tract (41%) and the oropharynx (23%) were the two most frequent presumed or proven sources for bacteraemia, with the origin remaining unknown in eight (20.5%) cases. The overall mortality rate (evaluated 7 days after the occurrence of bacteraemia) was 13%. Fatal outcome correlated with the severity of underlying diseases and the immunosuppressed status of the patients rather than with the causative pathogen or the effectiveness of antimicrobial therapy. Likewise, there was no difference in the mortality rate between patients with monomicrobial and polymicrobial bacteraemia. Overall, the data re-emphasise the importance of anaerobic bacteraemia, especially in patients with haematological malignancies.

Effects of antimicrobial therapy on the microbial flora of the adenoids.

The core of the adenoids contains polymicrobial aerobic and anaerobic flora and also includes potential respiratory pathogens. Similar flora, although in higher numbers and with a higher frequency of pathogens, are found in inflamed or hypertrophic adenoids and many of these bacteria are resistant to antimicrobial agents. Exposure to antimicrobial therapy can alter the colonization patterns and select for resistant organisms. Production of beta-lactamase is one of the major mechanisms of resistance of these organisms. The adenoids of healthy individuals, in contrast to those with recurrent respiratory tract infections, are generally colonized by aerobic and anaerobic organisms that are capable of interfering with the growth of potential pathogens. Maintaining the beneficial effects of normal flora by avoiding unnecessary exposure to antimicrobial therapy may be a useful tool in preventing colonization of the adenoids by potential pathogens. This review discusses the unique microbiology of the adenoids in individuals with a variety of pathological conditions, the interactions between the various organisms and the effects of antimicrobial therapy on the microbial flora of the adenoids.

Etiology and treatment of pneumonia.

Lower respiratory tract infections are a common cause of morbidity among children. Among these infections pneumonia is the most serious illness and can be difficult to diagnose. The etiology of pneumonia is still partly unknown, primarily because of difficulty in obtaining adequate samples and lack of reliable diagnostic methods. Streptococcus pneumoniae is recognized as an important cause of pediatric pneumonia regardless of age in both the inpatient and outpatient setting. In developed countries S. pneumoniae probably accounts for 25 to 30% of cases of pediatric community-acquired pneumonia. Viruses (mostly respiratory syncytial virus) are responsible for approximately 20% of cases, and Chlamydia pneumoniae and Mycoplasma pneumoniae occur commonly in older children. Despite the effectiveness of antimicrobial therapy, the emergence of resistant bacterial pathogens has resulted in increased interest in developing more effective vaccines. If conjugate pneumococcal vaccines prove effective at eradicating carriage of pneumococci in the nasopharynx, immunization may be an important tool against the spread of pneumococcal disease. Future challenges include implementation of effective intervention strategies, production of simple diagnostic tools and development of effective vaccines.

Antibiotic therapy in preterm premature rupture of membranes.

Good quality evidence supports the use of antibiotic therapy in women with preterm PROM for whom expectant management is planned. The best evidence supports the choice of an extended-spectrum agent or combination administered intravenously for 2 days followed by an extended spectrum or combination of oral agents for several more days. Despite the effectiveness of antimicrobial therapy in this setting, the potential risks of systemic antibiotic administration, such as allergic reactions, overgrowth of commensal organisms, and emergence of resistant pathogens, much always be kept in mind. Nevertheless, in the majority of cases, assuming the patient is a good candidate for expectant management, the benefits of antibiotic therapy outweigh the risks.