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An open randomised comparison of ofloxacin and doxycycline in lower respiratory tract infections.

The efficacy and tolerance of ofloxacin and doxycycline were compared in patients with lower respiratory tract infections. Doses used were 200 or 400mg twice daily for ofloxacin and 100mg twice daily for doxycycline. Of 230 patients treated, 219 could be assessed for effectiveness. 88 patients were treated for exacerbations of chronic bronchitis and 131 for pneumonia. Clinical cure was achieved in 18 of 52 patients with bronchitis treated with ofloxacin. Improvement occurred in 29 and failure in 5. In the doxycycline-treated bronchitis group 11 of 36 patients were cured, 22 improved and 1 failure occurred. Of 62 patients with pneumonia who were administered ofloxacin, 34 were cured, 26 improved and treatment failed in 2. In the doxycycline-treated group of patients with pneumonia 39 of 69 were cured, 23 improved and 7 failed to respond. Two patients experienced adverse effects during ofloxacin treatment and 7 while receiving doxycycline.

Anti-Infective Agents↗

Respiratory syncytial virus (RSV) immune globulin intravenous therapy for RSV lower respiratory tract infection in infants and young children at high risk for severe RSV infections: Respiratory Syncytial Virus Immune Globulin Study Group.

OBJECTIVES: To evaluate the efficacy of high-titer intravenous respiratory syncytial virus immune globulin (RSVIG) in the treatment of children at high risk for severe RSV infection who were hospitalized with proven RSV. METHODS: Infants and young children younger than 2 years with bronchopulmonary dysplasia, chronic lung disease, congenital heart disease, or prematurity (<32 weeks' gestational age), hospitalized with a history of lower respiratory tract infection (LRI) of less than 4 days, were enrolled in this study. Patients were randomized in a blinded fashion to receive either 1500 mg/kg RSVIG or placebo in equal volumes. They were evaluated daily for safety and respiratory scores and for RSV nasal shedding. RESULTS: One hundred seven high-risk children were randomized--54 in the RSVIG group and 53 in the placebo group. Of these children, 51 in each group were considered evaluable. Children with pulmonary disease, congenital heart disease, or prematurity were equally distributed between the two treatment groups. However, two important differences were found in baseline variables between the two groups: there were more patients in the placebo group who had histories of previous LRI and there was a trend toward more severe disease at study entry in the RSVIG group. This was manifested by a higher entry respiratory score in the RSVIG group than in the placebo group (3.4 +/- 0.2 vs 3.1 +/- .01). A higher proportion of children in the RSVIG group (47%) than in the placebo group (28%) required intensive care at entry and mechanical ventilation at study entry (31% RSVIG-treated vs 18% placebo-treated patients). No significant difference was found between groups in the mean unadjusted duration of hospitalization (RSVIG group, 9.10 +/- 1.18 days; control group, 8.17 +/- 1.08 days). When the mean was adjusted for entry respiratory score, likewise, no difference was observed between each group (8.41 +/- 0.97 vs 8.89 +/- .99 days). The lack of efficacy observed in the study primary endpoint was observed in all diagnostic groups. No differences between the RSVIG and placebo groups were observed in the following secondary endpoints: duration of intensive care unit stay, duration of intensive care unit stay for RSV, mechanical ventilation, or supplemental oxygen. No significant differences in adverse events were reported in the RSVIG group (16 children) when compared with the control group (10 children). CONCLUSION: RSVIG treatment was safe but not efficacious in the treatment of children with bronchopulmonary dysplasia, congenital heart disease, or premature gestation who were hospitalized with RSV LRI.

Bronchiolitis↗

An open, multicentre, comparative study of the efficacy and safety of azithromycin and co-amoxiclav in the treatment of upper and lower respiratory tract infections in children. The Paediatric Azithromycin Study Group.

An open prospective, multicentre, comparative, randomized (2:1) study was conducted in 481 children diagnosed as having mild-to-moderate lower respiratory tract infections. The efficacy and safety of azithromycin suspension (10 mg/kg), dosed orally once daily for 3 days, was compared with that of co-amoxiclav (10 mg/kg in a 4:1 ratio), dosed orally three times daily for 5-10 days. The proportion of evaluable patients (n = 472) showing a cure or improvement was significantly higher in the azithromycin group (96.8%) than in the co-amoxiclav group (91%, P = 0.0199). There were six relapses in both groups, giving an overall response rate of 95% for azithromycin versus 87.1% for co-amoxiclav (P = 0.0025). Adverse events were reported in 10% of the patients treated with azithromycin, and 11.3% of co-amoxiclav patients. Reported and counted compliance was significantly better in the azithromycin group. A 3-day regimen of azithromycin was as effective and as safe as a 5-10 day regimen of co-amoxiclav in the treatment of respiratory tract infections in children, and compliance was improved.

Adolescent↗

Community respiratory viruses as a cause of lower respiratory tract infections following suppressive chemotherapy in cancer patients.

BACKGROUND AND PURPOSE: Community respiratory viruses are an important cause of respiratory disease in the immunocompromised patients with cancer. To evaluate the occurrence and clinical significance of respiratory virus infections in hospitalized cancer patients at National Cancer Institute, Cairo University, during anticancer treatment, we studied cases that developed episodes of lower respiratory tract infections (LRTI). PATIENTS AND METHODS: Thirty patients with LRTI were studied clinically, radiologically, and microbiologically. Sputum cultures were done and an immunofluorescence search for IgM antibodies of influenza A and B, parainfluenza serotypes 1, 2 and 3, adenovirus, respiratory syncytial virus, Legionella pneumophila, Coxiella burnettii, Chlamydia pneumoniae, and Mycoplasma pneumoniae were performed on serum samples of patients. RESULTS: The main presenting symptom was cough and expectoration. Hematologic malignancy was the underlying disease in 86.6% of cases. Blood cultures were positive in 11 patients (36.6%) only. Sputum cultures revealed a bacterial pathogen in 13 cases and fungi in 3; whereas viral and atypical bacterial IgM antibodies were detected in 13 and 4 patients; respectively. Influenza virus was the commonest virus detected, being of type B in 4 cases, type A in one case and mixed A and B in another 5 cases; followed by RSV in 5 patients. Taken together, bacteria were identified as a single cause of LRTI in 10 cases, viruses in 6, fungi in 3 and mixed causes in 7. Still, there were 4 undiagnosed cases. CONCLUSIONS: This study showed that respiratory viruses are common in LRTI, either as a single cause or mixed with bacterial pathogens, in hospitalized cancer patients receiving chemotherapy. Diagnostic tests for respiratory viruses should be incorporated in the routine diagnostic study of patients with hematologic malignancies. Also, it must be emphasized that early CT chest is crucial as a base-line prior to initiation of anti-fungal or anti-viral therapy. In cancer patients with a febrile episode and LRTI, tailored therapy is recommended according to the clinical findings of the patient.

Adolescent↗

Randomized comparative study of ceftibuten versus cefaclor in the treatment of acute lower respiratory tract infections.

In a randomized, single-blind trial, ceftibuten in doses of 200 mg and 300 mg administered b.i.d., was compared with cefaclor 500 mg t.i.d. in acute lower respiratory tract infections. A total 545 patients were enrolled, of which 263 were evaluable for efficacy. All patients were adults with a diagnosis of either bacterial pneumonia or bronchitis. The infective organism was eliminated in 83% of the patients in the ceftibuten 200-mg b.i.d. treatment group and in 85% of patients in the 300-mg b.i.d. treatment group. The organisms were eliminated in 79% of cefaclor-treated patients. Satisfactory clinical responses were obtained in 91% of patients in the ceftibuten 200-mg b.i.d. treatment group and in 92% of patients in the ceftibuten 300-mg b.i.d. group. Satisfactory clinical responses were obtained in 91% of cefaclor-treated patients. Predominant pathogens isolated were Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and strains of Enterobacteriaceae. Adverse experiences reported were similar for the ceftibuten and cefaclor treatment groups. Gastrointestinal side effects occurred in 6% of patients treated with ceftibuten 200 mg BID, 9% in those treated with 300 mg BID, and 7% of cefaclor-treated patients. Ceftibuten 200 and 300 mg twice daily was as effective as cefaclor bacteriologically and clinically in the treatment of lower respiratory tract infections.

Acute Disease↗

Treatment of upper and lower respiratory tract infections: clinical trials with cefprozil.

The oral second generation cephalosporin cefprozil has a broad spectrum microbiologic profile, with good in vitro activity against respiratory pathogens; 90% or more of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates are susceptible to cefprozil. Clinical trials of cefprozil have consistently demonstrated good clinical success rates in upper and lower respiratory tract infections, including otitis media, sinusitis, pharyngitis/ tonsillitis and acute bacterial exacerbations of chronic bronchitis. Most recently cefprozil has demonstrated success in children with recurrent and persistent acute otitis media. Data from clinical trials including more than 4000 children and adults have shown that cefprozil is well-tolerated. The most common adverse events associated with cefprozil are gastrointestinal disturbances (i.e. diarrhea and nausea). In two patient satisfaction surveys (pediatric and adult), cefprozil was cited for having a low incidence of side effects and was rated by children as having a pleasing taste. These data indicate that cefprozil is a practical therapeutic choice for the treatment of upper and lower respiratory tract infections.

Adult↗

Signature-tagged mutagenesis of Klebsiella pneumoniae to identify genes that influence biofilm formation on extracellular matrix material.

Klebsiella pneumoniae causes urinary tract infections, respiratory tract infections, and septicemia in susceptible individuals. Strains of Klebsiella frequently produce extended-spectrum beta-lactamases, and infections with these strains can lead to relatively high mortality rates (approximately 15%). Other virulence factors include production of an antiphagocytic capsule and outer membrane lipopolysaccharide (LPS), which mediates serum resistance, as well as fimbriae on the surface of the bacteria. Type 1 fimbriae mediate adherence to many types of epithelial cells and may facilitate adherence of the bacteria to the bladder epithelium. Type 3 fimbriae can bind in vitro to the extracellular matrix of urinary and respiratory tissues, suggesting that they mediate binding to damaged epithelial surfaces. In addition, type 3 fimbriae are required for biofilm formation by Klebsiella pneumoniae on plastics and human extracellular matrix; thus, they may facilitate the formation of treatment-resistant biofilm on indwelling plastic devices, such as catheters and endotracheal tubing. The presence of these devices may cause tissue damage, allowing Klebsiella to grow as a biofilm on exposed tissue basement membrane components. Though in vivo biofilm growth may be an important step in the infection process, little is known about the genetic factors required for biofilm formation by Klebsiella pneumoniae. Thus, we performed signature-tagged mutagenesis to identify factors produced by K. pneumoniae strain 43816 that are required for biofilm formation. We identified mutations in the cps capsule gene cluster, previously unidentified transcriptional regulators, fimbrial, and sugar phosphotransferase homologues, as well as genetic loci of unknown function, that affect biofilm formation.

Animals↗

Treatment of severe lower respiratory tract infections with ceftriaxone (Ro 13-9904). A pilot study.

Two pilot comparative trials in 29 patients suffering from severe lower respiratory tract infections are described. 15 patients received 7-10.5 g ceftriaxone as a total dose and 14 received 28 g amoxicillin, both antibiotics being given by intravenous route during 1 week. The local and systemic tolerance of the drugs were satisfactory; no adverse reactions or relevant laboratory changes were noticed. The clinical response was favourable in all patients. The mot relevant pathogens found in the sputum were Streptococcus pneumoniae in 11 cases and Haemophilus influenzae in 15 cases. Less relevant microorganisms such as Klebsiella pneumonia, Serratia, Pseudomonas sp. and Streptococcus viridans were cultivated prior to therapy. The two main pathogens disappeared from the sputum after therapy in 11 of 13 patients treated with ceftriaxone and in 10 of 13 treated with amoxicillin. The results of these pilot studies indicate that 7-10.5 g ceftriaxone are as active as 28 g amoxicillin in the treatment of severe lower respiratory tract infections.

Adult↗

Identification of viruses in a study of acute respiratory tract infection in children from Uruguay.

For the purpose of identifying viral agents associated with acute respiratory tract infections (ARI) in children less than 5 years old, a longitudinal community study was undertaken in Montevideo, Uruguay, from May 1985 to December 1987. This report includes results obtained by cell culture and immunofluorescence techniques for detection of respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza 1 and 3 viruses, and adenovirus. Two populations were studied: children visited at home by pediatricians (group 1) and children with an ARI episode who attended an outpatient clinic (group 2). Nasopharyngeal aspirates were obtained at the time of an ARI episode: 858 from group 1 and 488 from group 2. Viruses were identified in 15.3% of group 1 specimens and in 17.6% of group 2 specimens. RSV was the most frequently recovered agent, accounting for 67.9% and 58.1%, respectively, of all viruses detected. The sensitivity and specificity of RSV isolation by cell culture are compared with detection by indirect immunofluorescence.

Acute Disease↗

A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico.

BACKGROUND: The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured. OBJECTIVE: We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics. DESIGN: A double-blind, randomized, placebo-controlled trial was carried out in which 736 children aged 6-15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo, zinc daily, vitamin A and zinc together, or placebo. Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections. RESULTS: Vitamin A supplementation was associated with a 27% increase in diarrheal disease [risk ratio (RR): 1.27; 95% CI: 1.10, 1.45; P < 0.001] and a 23% increase in cough with fever (RR: 1.23; 95% CI: 1.02, 1.47; P = 0.02), whereas zinc had no effect on these outcomes. Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors, piped water, and indoor bathrooms. Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated. Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers. CONCLUSIONS: Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City. Vitamin A and zinc have more heterogeneous effects in different subgroups of children.

Confidence Intervals↗

An outbreak of Bacillus cereus respiratory tract infections on a neonatal unit due to contaminated ventilator circuits.

An outbreak of Bacillus cereus respiratory tract infections affecting six ventilated preterm neonates over a two-week period is described. Reusable ventilator circuits were identified as the cause of the outbreak. Ordinarily these were reprocessed on the Neonatal Unit (NNU), first through a washing machine and then through a low-temperature steam (LTS) disinfector. The onset of the outbreak coincided with a breakdown of the LTS facility, which necessitated sending the washed circuits off site for LTS disinfection. The washing machine was shown to be contaminated with the same serovars of B. cereus as those isolated from patients. Two critical steps in the off site LTS disinfection process allowed exsporulation and multiplication of B. cereus: the circuits were inadequately dried after processing, whilst return of the moist circuits to the NNU was often delayed. The outbreak was terminated by withdrawal of the heat-disinfected ventilator circuits. This outbreak emphasizes the need for high standards where medical equipment is reprocessed, especially for use in vulnerable patients.

Bacillaceae Infections↗

Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with community-acquired respiratory tract infections.

Garenoxacin (T-3811ME, BMS-284756) is a novel, broad-spectrum des-F(6) quinolone currently under study for the treatment of community-acquired respiratory tract infections. This analysis assessed garenoxacin population pharmacokinetics and exposure-response relationships for safety (adverse effects [AE]) and antimicrobial activity (clinical cure and bacteriologic eradication of Streptococcus pneumoniae and the grouping of Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis). Data were obtained from three phase II clinical trials of garenoxacin administered orally as 400 mg once daily for 5 to 10 days for the treatment of community-acquired pneumonia, acute exacerbation of chronic bronchitis, and sinusitis. Samples were taken from each patient before drug administration, 2 h following administration of the first dose, and on the day 3 to 5 visit. Individual Bayesian estimates of the fu (fraction unbound), the Cmax, and the fu for the area under the concentration-time curve from 0 to 24 h (fu AUC(0-24)) were calculated as measurements of drug exposure by using an ex vivo assessment of average protein binding. Regression analysis was performed to examine the following relationships: treatment-emergent AE incidence and AUC(0-24), Cmax, or patient factors; clinical response or bacterial eradication and drug exposure (fu Cmax/MIC, fu AUC(0-24)/MIC, and other exposure covariates); or disease and patient factors. Garenoxacin pharmacokinetics were described by a one-compartment model with first-order absorption and elimination. Clearance was dependent on creatinine clearance, ideal body weight, age, obesity, and concomitant use of pseudoephedrine. The volume of distribution was dependent on weight and gender. Patients with mild or moderate renal dysfunction had, on average, approximately a 16 or 26% decrease in clearance, respectively, compared to patients of the same gender and obesity classification with normal renal function. AE occurrence was not related to garenoxacin exposure. Overall, clinical cure and bacterial eradication rates were 91 and 90%, respectively, for S. pneumoniae and 93 and 92%, respectively, for the grouping of H. influenzae, H. parainfluenzae, and M. catarrhalis. The fu AUC(0-24)/MIC ratios were high (>90% were >200), and none of the pharmacokinetic-pharmacodynamic exposure measurements indexed to the MIC or other factors were significant predictors of clinical or bacteriologic response. Garenoxacin clearance was primarily related to creatinine clearance and ideal body weight. Although garenoxacin exposure was approximately 25% higher for patients with moderate renal dysfunction, this increase does not appear to be clinically significant as exposures in this patient population were not significant predictors of AE occurrence. Garenoxacin exposures were at the upper end of the exposure-response curves for measurements of antimicrobial activity, suggesting that 400 mg of garenoxacin once daily is a safe and adequate dose for the treatment of the specified community-acquired respiratory tract infections.

Adolescent↗

Efficacy and safety of aztreonam-clindamycin versus tobramycin-clindamycin in the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli.

A total of 80 patients were randomized to receive either aztreonam or tobramycin for the treatment of lower respiratory tract infections caused by gram-negative bacilli; all these patients received clindamycin concomitantly. A total of 53 patients were randomized to receive aztreonam-clindamycin; of these, 46 were clinically evaluable and 39 were bacteriologically evaluable. Of the 46 clinically evaluable patients, 41 were considered cured, 3 failed to be cured, and 2 died during the study period of unrelated causes. Of the 39 bacteriologically evaluable patients, 36 were considered cured, and 3 failed to be cured. There were 26 clinically evaluable patients in the group randomized to receive tobramycin-clindamycin. Of them, 22 patients were considered cured, 3 failed to be cured, and 1 died of unrelated causes during the study period. There were 18 bacteriologically evaluable patients in the tobramycin-clindamycin group; 17 were cured, and 1 failed to be cured. The most common pathogens isolated from the patients were Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. All of the isolated organisms were susceptible to both tested antibiotics, except for a strain of Pseudomonas cepacia resistant to both tested antimicrobial agents and a strain of Enterobacter aerogenes and one of P. aeruginosa that were resistant to aztreonam. Very few adverse reactions related to the antibiotics were seen. These effects, when present, were transient and comparable in both studied groups, except for renal-function tests, which were altered in 7.7% of the patients randomized to receive tobramycin-clindamycin and in none of the patients randomized to receive aztreonam-clindamycin. Aztreonam-clindamycin is safe and effective for the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli when the organisms are susceptible.

Aged↗

Levamisole (R 12564) in the prevention of recurrent upper respiratory tract infections in children: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled trial was carried out in 33 children suffering from chronic or recurrent upper respiratory tract infections to assess the effectiveness of levamisole in reducing the number, duration, and severity of infective episodes. A weight-related dosage of levamisole was used (2.0 to 2.5 mg per kg body weight), patients taking a single dose on 1 day per week over an autumn-winter period of 4 months. The results showed that patients in the levamisole-treated group had statistically significantly fewer periods of upper respiratory tract infection and when they occurred the episodes were milder and shorter in the levamisole group and required less antibiotics. No side-effects were noted.

Child↗

[The course of post-streptococcal glomerulonephritis depending on methods of treatment for the preceding respiratory tract infection].

UNLABELLED: The aim of our work was to assess the course of post-streptococcal glomerulonephritis (APSGN) in children according to the way of preceding respiratory tract infection treatment. The examinations were carried out in a group of 26 children aged 5-15 years, who were divided into two subgroups: I--12 children, who did not receive antibacterial treatment, and II--14 children who were shortly treated with different antibiotics (3-5 days). All the children had full symptomatic picture of post-streptococcal glomerulonephritis with haematuria, oedemas, hypertension and hypocomplementemia. The etiology was diagnosed retrospectively during observation of ASO titer dynamics and additionally in 18 after finding pathogenic Streptococcus strains in pharyngeal swab. The differences in the course of illness was shown only during first weeks. In children from the group I the course of acute APSGN was a little more serious, because haematuria, proteinuria and hypertension were observed longer. Symptoms of nephrotic syndrome were observed in two children, acute renal insufficiency in two children, and one with hypertensive encephalopathy. After 3 and 12 months no children had pathological signs. Erythrocyturia was observed in 19 of 26 children after 3 months and in 10 of 26 children after 12 months after illness with similar frequency in both groups. In 5 children with proteinuria renal biopsy showed mesangialis proliferative glomerulonephritis--1st degree. CONCLUSION: All observed children with APSGN were not cured properly during the respiratory tract infection preceding the disease, however even short antibacterial treatment caused the moderation of symptoms.

Adolescent↗

Antibiotic kinetic and dynamic attributes for community-acquired respiratory tract infections.

Factors, including the age of the treatment population, this population's multiple comorbidities, the greater severity of their illness, and the considerable change in the pathogens in their epidemiology and resistance patterns, affect the management of community-acquired respiratory tract infections in the outpatient setting. Moreover, outcome is affected by the host, etiologic agent, and the selection of the antimicrobial treatment. The challenge of selecting appropriate antimicrobial therapy is often at the discretion of the prescriber. The nature of respiratory tract infections and the relationship of antimicrobial therapy to the resolution of infection are described.

Anti-Bacterial Agents↗

[Efficacy and tolerability of cefixime in lower respiratory tract infections in adults. French multicentric study].

Cefixime is a new oral cephalosporin with the same activity as that of third generation cephalosporins, particularly against organisms responsible for lower respiratory tract infections. The effectiveness and safety of cefixime were evaluated in the multicentre study reported here. Cure was obtained in 54 of 61 assessable patients suffering from bronchopneumonia (40/44), acute bronchitis (3/5) or acute exacerbations of chronic bronchitis (11/12). The causative agents were eradicated in 35 of 41 assessable cases. No clinical side-effect was observed. Thrombocytosis without clinical manifestations was reported in 14 cases. Administered in doses of 200 mg twice daily, cefixime proved effective and safe in the treatment of lower respiratory tract infections.

Acute Disease↗

Role of oral antibiotics in treatment of community-acquired lower respiratory tract infections.

Amoxicillin/clavulanic acid has been one of the first choice treatments for community-acquired lower respiratory tract infection since its introduction nearly 15 years ago. Since then, it has become the "gold standard" against which most new oral antimicrobials are compared, but none of these newer agents has demonstrated a superior efficacy. To the contrary, two recent studies comparing amoxicillin/clavulanic acid with azithromycin, cefixime, or ciprofloxacin in the treatment of acute exacerbations of chronic bronchitis have demonstrated a higher efficacy rate for amoxicillin/clavulanic acid.

Anti-Bacterial Agents↗