Clindamycin plus gentamicin as expectant therapy for presumed mixed infections.
The prevalence of obligate anaerobes was studied prospectively in 60 patients with severe sepsis of intra-abdominal, soft tissue, female genital or oropulmonary origin. In addition, the efficacy of clindamycin (for anaerobes) plus gentamicin (for aerobic bacteria, especially coliforms) as initial empiric therapy in these patients was evaluated. Among 54 patients with cultural proof of infection, anaerobic pathogens were recovered from 52%. Nineteen patients had bacteremia; Bacteroides fragilis and Klebsiella pneumoniae were the most prevalent pathogens, being isolated in five patients each. Infection was eradicated in 56 of the 60 patients (93%). Mortality related to sepsis was 7% in the entire group, 16% in patients with bacteremia and 2% in patients without bacteremia. Eighty-five percent of aerobic isolates tested were susceptible in vitro to either gentamicin or clindamycin; 97% of anaerobic isolates were inhibited by 5 mug/ml of clindamycin. (+info)
Route and type of nutrition influence mucosal immunity to bacterial pneumonia.
OBJECTIVE: To develop a model of established respiratory immunity against Pseudomonas aeruginosa pneumonia and to investigate the effects of route and type of nutrition on this immunity. SUMMARY BACKGROUND DATA: Diet influences the ability of gut-associated lymphoid tissue (GALT) to maintain mucosal immunity. Complex enteral diets and chow maintain normal GALT populations against established IgA-mediated antiviral respiratory immunity. Both intravenous and intragastric total parenteral nutrition (TPN) produce GALT atrophy, but only intragastric TPN preserves established antiviral immunity. The authors hypothesized that both GALT-depleting diets (intragastric and intravenous TPN) would impair immunity against bacterial pneumonia. METHODS: P. aeruginosa was administered intratracheally to determine the mortality rate at increasing doses, and liposomes containing P. aeruginosa antigens were used to generate effective respiratory immunization. In the final experiment, mice received liposomes containing P. aeruginosa antigens to establish immunity and then were randomized to chow, complex enteral diets, intragastric TPN, or intravenous TPN. After 5 days of diet, mice received live intratracheal P. aeruginosa, and the death rate was recorded at 24 and 48 hours. RESULTS: The LD50 and LD100 were 9 x 10(7) and 12 x 10(7), respectively. Immunization reduced the mortality rate from 66% to 12%. This immunization was maintained in mice fed chow or a complex enteral diet and was lost in animals receiving intravenous TPN. Intragastric TPN partially preserved this respiratory immunity. CONCLUSIONS: Protection against bacterial pneumonia can be induced by prior antigenic immunization. This protection is lost with intravenous TPN, partially preserved with a chemically defined enteral diet, and completely preserved with chow or complex enteral diets. Both route and type of nutrition influence antibacterial respiratory tract immunity. (+info)
Cystic fibrosis transmembrane conductance regulator-mediated corneal epithelial cell ingestion of Pseudomonas aeruginosa is a key component in the pathogenesis of experimental murine keratitis.
Previous findings indicate that the cystic fibrosis transmembrane conductance regulator (CFTR) is a ligand for Pseudomonas aeruginosa ingestion into respiratory epithelial cells. In experimental murine keratitis, P. aeruginosa enters corneal epithelial cells. We determined the importance of CFTR-mediated uptake of P. aeruginosa by corneal cells in experimental eye infections. Entry of noncytotoxic (exoU) P. aeruginosa into human and rabbit corneal cell cultures was inhibited with monoclonal antibodies and peptides specific to CFTR amino acids 108 to 117. Immunofluorescence microscopy and flow cytometry demonstrated CFTR in the intact murine corneal epithelium, and electron microscopy showed that CFTR binds to P. aeruginosa following corneal cell ingestion. In experimental murine eye infections, multiple additions of 5 nM CFTR peptide 103-117 to inocula of either cytotoxic (exoU+) or noncytotoxic P. aeruginosa resulted in large reductions in bacteria in the eye and markedly lessened eye pathology. Compared with wild-type C57BL/6 mice, heterozygous DeltaF508 Cftr mice infected with P. aeruginosa had an approximately 10-fold reduction in bacterial levels in the eye and consequent reductions in eye pathology. Homozygous DeltaF508 Cftr mice were nearly completely resistant to P. aeruginosa corneal infection. CFTR-mediated internalization of P. aeruginosa by buried corneal epithelial cells is critical to the pathogenesis of experimental eye infection, while in the lung, P. aeruginosa uptake by surface epithelial cells enhances P. aeruginosa clearance from this tissue. (+info)
The sialylation of bronchial mucins secreted by patients suffering from cystic fibrosis or from chronic bronchitis is related to the severity of airway infection.
Bronchial mucins were purified from the sputum of 14 patients suffering from cystic fibrosis and 24 patients suffering from chronic bronchitis, using two CsBr density-gradient centrifugations. The presence of DNA in each secretion was used as an index to estimate the severity of infection and allowed to subdivide the mucins into four groups corresponding to infected or noninfected patients with cystic fibrosis, and to infected or noninfected patients with chronic bronchitis. All infected patients suffering from cystic fibrosis were colonized by Pseudomonas aeruginosa. As already observed, the mucins from the patients with cystic fibrosis had a higher sulfate content than the mucins from the patients with chronic bronchitis. However, there was a striking increase in the sialic acid content of the mucins secreted by severely infected patients as compared to noninfected patients. Thirty-six bronchial mucins out of 38 contained the sialyl-Lewis x epitope which was even expressed by subjects phenotyped as Lewis negative, indicating that at least one alpha1,3 fucosyltransferase different from the Lewis enzyme was involved in the biosynthesis of this epitope. Finally, the sialyl-Lewis x determinant was also overexpressed in the mucins from severely infected patients. Altogether these differences in the glycosylation process of mucins from infected and noninfected patients suggest that bacterial infection influences the expression of sialyltransferases and alpha1,3 fucosyltransferases in the human bronchial mucosa. (+info)
Cellular fatty acids and metabolic products of Pseudomonas species obtained from clinical specimens.
The cellular fatty acid composition of 112 reference strains and clinical isolates of Pseudomonas species was determined by gas-liquid chromatography (GLC). The presence and relative amounts of cyclopropane, hydroxy, and branched-chain fatty acids were distinguishing features of these strains. Determination of short-chain fatty acids extracted from spent growth media provided an additional means for identifying some strains. Our results show that clinical isolates of pseudomonads can be divided into eight distinct GLC groups. The procedures were especially useful for distinguishing glucose-nonoxidizing pseudomonads, which are difficult to identify by conventional criteria. Since the GLC procedures are simple, rapid, and highly reproducible, they are useful in diagnostic laboratories that process large numbers of cultures. Coupled with selected conventional tests, the analysis of short-chain and cellular fatty acids can be very useful for rapid screening of clinical isolates of Pseudomonas species. (+info)
Pathogenesis of experimental Pseudomonas keratitis in the guinea pig: bacteriologic, clinical, and microscopic observations.
Uniformly severe corneal infections were produced in guinea pigs by intracorneal injection of about 10 viable Pseudomonas aeruginosa. After a brief lag period, multiplication of bacteria was rapid, reaching geometric means of 280,000 after 24 hr and of 5 million after 48 hr. Within 8 hr after inoculation, polymorphonuclear leukocytes (PMNs) began to infiltrate the anterior two thirds of the stroma. Stromal cells adjacent to the injection site became necrotic and appeared to be engulfed by PMNs. By 14 to 16 hr, an abscess containing a dense aggregate of PMNs and multiplying bacteria developed in the central stroma. By 16 to 24 hr, collagen breakdown was apparent within and around the abscess. Ultrastructural evidence of collagen breakdown included loss of intact collagen fibrils, tactoid formation, and accumulation of amorphous electron-dense material. The area of liquefactive necrosis gradually enlarged, and many corneas perforated after 3 to 4 days. Because the course of infection is highly reproducible, this model should prove useful for many studies of experimental Pseudomonas keratitis. (+info)
Bacteriologic cure of experimental Pseudomonas keratitis.
Two long-term therapy trials with high concentrations of antibiotic were carried out to determine the duration of therapy required to achieve bacteriologic cure of experimental Pseudomonas keratitis in guinea pigs. In the first study, corneas still contained Pseudomonas after 4 days of continual topical therapy with either tobramycin 400 mg/ml, amikacin 250 mg/ml, ticarcillin 400 mg/ml, or carbenicillin 400 mg/ml. In an 11-day trial of topical therapy with tobramycin 20 mg/ml, 34 of 36 corneas grew no Pseudomonas after 6 or more days of therapy. The bacteriologic response to therapy in this model occurred in two phases. About 99.9% or more of the organisms in the cornea were killed in the first 24 hr of therapy. The numbers of bacteria remaining in the cornea declined gradually over the next several days until the corneas were sterile. Optimal antibiotic therapy may include two stages: initial intensive therapy with high concentrations of antibiotic applied frequently to achieve a large rapid decrease in numbers of organisms in the cornea, followed by prolonged, less intensive therapy to eradicate organisms and prevent relapse. (+info)
Comparison of flagellin genes from clinical and environmental Pseudomonas aeruginosa isolates.
Pseudomonas aeruginosa, an important opportunistic pathogen, was isolated from environmental samples and compared to clinically derived strains. While P. aeruginosa was isolated readily from an experimental mushroom-growing unit, it was found only rarely in other environmental samples. A flagellin gene PCR-restriction fragment length polymorphism analysis of the isolates revealed that environmental and clinical P. aeruginosa strains are not readily distinguishable. The variation in the central regions of the flagellin genes of seven of the isolates was investigated further. The strains used included two strains with type a genes (998 bp), four strains with type b genes (1,258 bp), and one strain, K979, with a novel flagellin gene (2,199 bp). The route by which flagellin gene variation has occurred in P. aeruginosa is discussed. (+info)