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[Demethyl-vancomycin in treatment of resistant staphylococcal infections. A clinical evaluation].

77 patients with serious resistant staphylococcal infections, including septicemia, lower respiratory infection, intraabdominal infection, skin and soft tissue infections and urinary tract infection, were treated with demethyl-vancomycin. 82% of the organisms were methicillin-resistant. Most of the patients had severe underlying diseases and were immunocompromised hosts. The infections were serious. The clinical efficacy rate was 73% and the bacteria clearance rate 68%. Mild adverse reactions happened in 11% of the patients and no obvious nephrotoxicity was noted. MIC90 of demethyl-vancomycin against staph. aureus was 2 micrograms/ml. All isolates in this study were highly susceptible to the drug. Demethyl-vancomycin was found more active against staphylococcus than the other 16 antibacterial agents, which are commonly used in this country. The indication and the use of the drug were discussed.

Adolescent↗

Staphylococcal alpha-toxin causes increased tracheal epithelial permeability.

Staphylococcus aureus is an important cause of pulmonary infections. The role of S. aureus alpha-toxin as a virulence factor is unclear. We hypothesized that airway epithelium is a target of S. aureus alpha-toxin and that exposure of airway epithelium to alpha-toxin results in damage to the airway epithelium. To examine the hypothesis that alpha-toxin is capable of independently producing airway epithelium damage as measured by permeability and morphometry, an isolated whole mouse trachea test apparatus was developed. In vitro epithelial permeability (P) was calculated and digital micrographs were analyzed morphometrically. Purified S. aureus alpha-toxin produced a significant increase in tracheal epithelial P (P < 0.05). Morphometric analysis revealed the ratio of adherent tracheal epithelium attached to the basement membrane divided by the total length of the basement membrane decreased in a dose-dependent manner with 1 microg/ml alpha-toxin and 10 microg/ml alpha-toxin (P < 0.05). We developed a novel isolated whole mouse trachea test apparatus for the measurement of tracheal epithelium damage. Increased P and separation of the tracheal epithelium from the basement membrane occurred after S. aureus alpha-toxin exposure. We conclude that mammalian airway epithelium is a target of S. aureus alpha-toxin.

Animals↗

Changes in strategies for optimal antibacterial therapy in cystic fibrosis.

Aggressive antibiotic therapy of bacterial airway infection is one of the main reasons for the dramatic increase in life expectancy over the last few decades. Staphylococcus aureus and Haemophilus influenzae are the predominant pathogens in younger patients, but the choice of antibiotic therapy against these pathogens remains highly controversial. There is general agreement that patients with pulmonary exacerbations should be treated and many cystic fibrosis (CF) centres will also try to eradicate bacteria in the absence of symptoms. Prophylactic antibiotic therapy, with anti-staphylococcal medications started at the time of diagnosis, is advocated by some groups but its positive effect remains unproven. In fact, recent studies have suggested that continuous prophylactic treatment with anti-staphylococcal antibiotics may increase the risk of early colonisation with Pseudomonas aeruginosa. P. aeruginosa is the main pathogen in older children with CF. While chronic airway infection with mucoid P. aeruginosa is considered irreversible, both the combination of oral ciprofloxacin with inhaled colistin and inhaled tobramycin alone has been used successfully in the early phase of colonisation. In patients chronically infected with P. aeruginosa, standard treatment of pulmonary exacerbations consists of intravenous combination therapy for 2-3 weeks. Controversy exists whether this treatment should be performed routinely every 3 months or only in the presence of a pulmonary exacerbation. Inhaled antibiotics such as tobramycin have been shown to improve lung function and reduce sputum density of P. aeruginosa, but both the optimal dose and the duration of therapy are unclear at the present time.

Anti-Bacterial Agents↗

Effect of subcutaneous injection of ginseng on cows with subclinical Staphylococcus aureus mastitis.

Cows with subclinical mastitis caused by Staphylococcus aureus were subjected to subcutaneous injections with either an extract from the root of Panax ginseng CA Meyer at a dose of 8 mg/kg body weight per day for 6 days, or with saline as a control. The injection areas were checked for adverse reactions. The daily milk production was measured before and after treatment. Blood was collected for total and differential leucocyte counts, identification of lymphocyte subpopulations using flow cytometry, lymphocyte proliferation test, and neutrophil phagocytosis and oxidative burst assay. Quarter milk samples were collected for bacteriological analysis and somatic cell counts (SCC). After the end of treatment, the numbers of S. aureus-infected quarters and milk SCC tended to decrease in ginseng-treated cows. Phagocytosis and oxidative burst activity of blood neutrophils were significantly increased 1 week after ginseng treatment, but the proliferative response of blood lymphocytes did not change significantly. The number of monocytes in ginseng-injected cows was significantly higher 1 week post-treatment than pre-treatment, and the number of lymphocytes was significantly higher than pre-infusion at 2 and 3 weeks after ginseng treatment. Similar changes were not observed in the control group. The present findings indicate that ginseng treatment can activate the innate immunity of cows and may contribute to the cow's recovery from mastitis. It is therefore suggested that ginseng has a potential as a stimulator of the immune system of dairy cows.

Animals↗

Milk complement and the opsonophagocytosis and killing of Staphylococcus aureus mastitis isolates by bovine neutrophils.

Phagocytosis of bacteria by bovine polymorphonuclear neutrophils (PMN) has long been regarded as essential for host defense against mastitis infection. Complement-mediated opsonisation by complement component 3 (C3) binding is an important component of the innate immune system. We investigated the role of milk complement as an opsonin and its involvement in the phagocytosis and killing of Staphylococcus aureus isolates from cases of bovine mastitis by bovine blood PMN. We show that deposition of milk C3 component occurred on six different isolates of S. aureus and that the alternative pathway was the sole complement pathway operating in milk of uninflamed mammary gland. This deposition was shown to occur at the same location as the capsule, but not on capsular antigen. Milk complement enhanced the chemiluminescence response of PMN induced by S. aureus. Nevertheless, the association of S. aureus to cells and the overall killing of bacteria by bovine PMN were not affected by the presence of milk complement. Therefore, as all milk samples contained antibodies to capsular polysaccharide type 5 and to other surface antigens, it is likely that milk antibodies were responsible for these two phagocytic events. Results of this study suggest that the deposition of milk complement components on the surface of S. aureus does not contribute to the defence of the mammary gland against S. aureus.

Animals↗

Enhanced clearance of a multiple antibiotic resistant Staphylococcus aureus in rats treated with PGG-glucan is associated with increased leukocyte counts and increased neutrophil oxidative burst activity.

PGG-Glucan [Betafectin], a highly purified soluble beta-(1-6)-branched beta-(1 3)-linked glucan isolated from Saccharomyces cerevisiae, has broad in vitro and in vivo anti-infective activities unrelated to cytokine induction. Here we present in vivo results on the anti-infective activity of PGG-Glucan against a multiple antibiotic resistant Staphylococcus aureus. PGG-Glucan (0.25-4 mg/kg) was administered intramuscularly to male Wistar rats 48 h, 24 h, and 4 h before and 4 h after intraperitoneal implantation of a gelatin capsule containing 10(8)S. aureus colony forming units (CFU). Blood samples were collected at various times after challenge to determine CFU levels, leukocyte counts and neutrophil oxidative burst activity; serum TNF-alpha, and IL-1beta levels were also evaluated. The 0.25 mg/kg PGG-Glucan dose had no effect on reducing blood CFU levels; however, PGG-Glucan doses of 0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg significantly reduced blood CFU levels by 48 h after challenge. Reduced CFU levels correlated with significantly elevated absolute monocyte counts, absolute neutrophil counts, and neutrophil oxidative burst activity in the absence of any effect on TNF-alpha or on IL-1beta levels. In additional studies, effects on mortality and blood CFU levels were evaluated in rats treated with ampicillin (an antibiotic to which the S. aureus was resistant), PGG-Glucan, or both agents. Mortality and blood CFU levels were reduced most in combination-treated rats compared to saline control rats or rats treated with either ampicillin alone or PGG-Glucan alone. We conclude that in vivo (1) PGG-Glucan can enhance clearance of an antibiotic resistant S. aureus, (2) that this clearance is accompanied by an increase in monocytes and neutrophils as well as a potentiation of neutrophil oxidative microbiocidal activity without alteration of the proinflammatory cytokine response, and (3) PGG-Glucan can enhance the effectiveness of traditional antibiotic treatment.

Absorption↗

Unique epidemiology of nosocomial infection in a children's hospital.

A prospective study of the epidemiology of nosocomial infections was undertaken in a large pediatric hospital. Infections were identified during a 12-month period with the use of medical record audits, indices identifying high-risk patients, and analysis of positive cultures and rapid diagnostic tests for viruses, fungi, and bacteria. The attack rate of the entire hospital population surveyed was 4.1 nosocomial infections per 100 patients discharged. In contrast with studies of patients in general hospitals that included comparatively few children, the most common sites of nosocomial infections were the respiratory and gastrointestinal tracts. Staphylococcus aureus was the most commonly isolated pathogen. However, rotavirus was identified more frequently than Escherichia coli, and documented viral infections were more common than infections caused by gram-negative bacilli.

Child↗

Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis.

As collections of lower respiratory tract specimens from young children with cystic fibrosis (CF) are difficult, we determined whether oropharyngeal cultures predicted lower airway pathogens. During 1992-1994, 75 of 90 (83%) infants with CF diagnosed by neonatal screening had 150 simultaneous bronchoalveolar lavage (BAL) and oropharyngeal specimens collected for quantitative bacterial culture at a mean age of 17 months (range, 1-52). Ten children undergoing bronchoscopy for stridor served as controls. Total and differential cell counts and interleukin-8 concentrations were measured in BAL fluid. A subset of bacterial pathogens were typed by pulsed field gel electrophoresis. A non-linear relationship with inflammatory markers supported a diagnosis of lower airway infection when > or = 10(5) colony-forming units/ml were detected. This criterion was met in 47 (31%) BAL cultures from 37 (49%) children. Staphylococcus aureus (19%), Pseudomonas aeruginosa (11%), and Hemophilus influenzae (8%) were the major lower airway pathogens. In oropharyngeal cultures, S. aureus (47%), Escherichia coli (23%), H. influenzae (15%), and P. aeruginosa (13%) predominated. The sensitivity, specificity, and positive and negative predictive values of oropharyngeal cultures for pathogens causing lower respiratory infections were 82%, 83%, 41%, and 97%, respectively. When there was agreement between paired oropharyngeal and BAL cultures, genetic fingerprinting showed some strains of the same organism were unrelated. We conclude that oropharyngeal cultures do not reliably predict the presence of bacterial pathogens in the lower airways of young CF children.

Bacteriological Techniques↗

Prophylactic antibiotics in cystic fibrosis: a conviction without evidence?

Pulmonary infection with Staphylococcus aureus occurs in young children with cystic fibrosis, and may contribute to the cycle of infection, inflammation, and destruction of lung tissue which leads to bronchiectasis. Practice guidelines in North America and the UK differ greatly with regard to the advice given on prescribing prophylactic antistaphylococcal antibiotics to young children with cystic fibrosis. This article reviews the evidence behind these guidelines, and suggests a pragmatic approach to clinical practice. The implications for research are also discussed, and suggestions are made for clinical trials to inform future guidelines.

Antibiotic Prophylaxis↗

Comparative activity of ofloxacin with reference to bacterial strains isolated in in-patients and out-patients.

The in vitro activity of ofloxacin, a new quinolone derivative, was compared to that of other agents commonly in use against pathogens isolated in the community and in the hospital. None of the community or hospital strains isolated from urinary tract infection showed resistance to ofloxacin, while variable resistance was demonstrable with all other oral agents. Similar results were obtained with pathogens isolated from infected wounds originating in the community and in the hospital. Among pathogens isolated from the respiratory tract, ofloxacin was most active against Haemophilus influenzae, but less active than the penicillin-cephalosporin group against Streptococcus pneumoniae. Ofloxacin was active against all but one (Pseudomonas aeruginosa) blood culture isolates. Of 112 strains isolated from community-acquired infections, only one strain was ofloxacin-resistant while resistance to sulphamethoxazole-trimethoprim, ampicillin and doxycycline was 34%, 42% and 30%, respectively. Among 219 pathogens originating from nosocomial infections, 3.2% were resistant to ofloxacin compared to 56% for cefazolin, to 7.2% for cefotaxime, 15.8% for piperacillin and 22.3% for gentamicin. These results suggest that ofloxacin has great therapeutic potential for the therapy of bacterial infections originating both in the community and in the hospital.

Anti-Bacterial Agents↗

[Therapy of chronic respiratory tract infections in children, including mucoviscidosis (author's transl)].

In respiratory tract infections in children a distinction must be made between frequently recurring infections and genuine chronic infections due to specific anatomical factors, immunological defects or congenital diseases such as mucoviscidosis. The most frequent pathogens are Haemophilus influenzae, pneumococci, Staphylococcus aureus, Streptococcus pyogenes, enterococci, Pseudomonas aeruginosa and Klebsiella, S. aureus predominates in infants. The same applies for mucoviscidosis, in which P. aeruginosa is the second most frequent pathogen, occurring frequently after a primary infection with staphylococci. In order to avoid frequent relapses in mucoviscidosis patients, uninterrupted long-term treatment with an antibiotic which is effective against staphylococci is recommended, commencing the moment the diagnosis has been established. Suitable antibiotics are co-trimoxazole or oral cephalosporins (e. g. cephalexin, cephradine or cefaclor). Other respiratory tract infections should be treated according to the antibiogramme with a suitable antibiotic once the diagnosis has been confirmed.

Cephalosporins↗

Infectious disease management with oral antibiotics.

This paper has reviewed the bacterial etiologies and therapeis for commonly seen infections in the out-patient clinic or physician's office. The use of oral antibiotics for the treatment of pharyngitis, otitis media, sinusitis, bronchitis, certain pneumonias, cellulitis, urinary tract infections and as follow-up therapy to systemic administration is discussed. Emphasis on the decreasing bacterial spectra of the tetracyclines is noted as well as a discussion of therapy of infections due to beta-lactamase-producing Staphylococcus aureus and Haemophilus influenzae.

Administration, Oral↗

Treatment of respiratory tract infections with pefloxacin in critically ill patients hospitalized in a surgical intensive care unit.

Respiratory tract infections were treated with pefloxacin in fifteen patients, who were hospitalized in the intensive care unit and required artificial ventilation. The treatment was successful in ten patients. Development of resistance was observed in Staphylococcus aureus (two times) and Pseudomonas aeruginosa (four times). No adverse reactions were seen.

Bacterial Infections↗

Fatal influenza A infection with Staphylococcus aureus superinfection in a 49-year-old woman presenting as sudden death.

A fatal case of influenza A infection with Staphylococcus aureus superinfection in a previously healthy 49-year-old woman presenting as sudden, unexpected death is reported. Autopsy revealed severe necrotizing tracheobronchitis and hemorrhagic pneumonia. Microscopic examination of the trachea and bronchi showed mucosal necrosis and a dense lympho-monocytic infiltration of all layers. The lungs showed focal hemorrhagic pneumonia. No pathological changes were detectable in the myocardium. Influenza A virus was detected in bronchi and lung samples obtained during autopsy by the polymerase chain reaction (PCR) and bacterial superinfection with Staphylococcus aureus was shown by culturing from tracheal, bronchial and pulmonary swabs obtained during autopsy. PCR assays for the detection of Panton-Valentine leukocidin performed from all samples were negative. This case demonstrates the need for an interdisciplinary approach towards an organism-specific diagnosis of potentially infection-related deaths undergoing a medico-legal autopsy. With improved diagnostic possibilities such as PCR and DNA sequencing, forensic pathologists can, in close association with the field of microbiology, make a significant contribution to the detection of highly infectious agents which must be notified to the authorities. This will increase particularly the knowledge about the influence of these agents on sudden, unexpected deaths in outpatients.

Death, Sudden↗