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Short survey of vaccination programmes for rabbits and fur animals and of vaccines, available in Western Germany. Rabbits: myxomatosis, pasteurella infection, dysenteria; mustelides (mink, polecat a.o.): distemper, virus enteritis, botulism, pseudomonas infection; fox: leptospirosis, distemper, fox encephalitis; ocelot: panleukopenia; chinchilla: pseudomonas infection, coli infection, yersinia infection.
Tobramycin (TOB) was administrated by intravenous drip infusion for 1 hour, to 15 patients with intractable chronic respiratory tract infections due to P. aeruginosa, and the following results were obtained. 1. Criteria of clinical effects We have made new criteria for the evaluation of the therapeutic effects on respiratory tract infections (Tables 1, 2). Clinical items were divided into 4 grades and radiographic ones into 6 to 11 grades. Each item was separately scored as followed; excellent was scored as 1 point when 3 or more grade upward-shifts were seen after treatment, good as 2 points in case of 2 grade upward-shifts, fair as 3 points in case of 1 grade upward-shift, unchanged as 4 points in case of no shift, impairment as 5 points in case of downward-shift. The integrated evaluation of the items was made according to the average points for the evaluated items; overall excellent was 1.9 or less, overall good 2.0 to 2.9, overall fair 3.0 to 3.5 and overall poor as 3.6 or more. 2. Clinical effects Overall clinical effects were evaluated as good in 7 cases, fair in 4 and poor in 4 out of 15 patients, and rate of good score was 46.7%. According to the dosage groups, rate of good score was 50% in the dose of 60 mg three times a day, 0% in the dose of 90 mg twice a day and 62.5% in the dose of 120 mg twice a day. Eradication rate of P. aeruginosa was 33.3%. Neither adverse side effects nor abnormal laboratory findings were observed.
To investigate the clinical incidence of inducible beta-lactamase, we measured the beta-lactamase activity in the sputum of 5 patients with chronic respiratory tract infection due to P. aeruginosa, by using the spectrophotometric method. During the piperacillin (PIPC) therapy given twice a day with a single dose of 2-3 g, sputum samples were collected every 2 hours for 3 days, and on the second day, two grams of Cefmetazole (CMZ) was added to PIPC therapy. The antibiotics concentration of each collected sputum samples were also measured by HPLC. In one out of 5 patients, no beta-lactamase activity in sputum was detected throughout the 3 days. However in three out of 5 patients, after the addition of CMZ to PIPC, the beta-lactamase activity significantly increased 2-3 times (max: 0.03 units/ml) that on PIPC alone, and gradually decreased on the 3rd day when PIPC was given alone. Then the peak concentration of PIPC with the addition of CMZ decreased to 38-73%, compared with that of PIPC alone. These findings were supported by the fact that CMZ showed a high in vitro inducer activity against the isolates from the sputum. In the remaining one patient, high beta-lactamase activity (mean: 0.16 units/ml) and no antibiotics concentration was detected to be constant throughout the 3 days, and it was confirmed for the reason that one of the isolates constitutively produced large amounts of beta-lactamase. These results suggest that inducible and constitutive beta-lactamase would clinically cause undesirable effects in the treatment by some beta-lactams and have a possibility of indirect pathogenesis.
The iron concentration of the culture medium used to prepare the inocula influenced the pathogenesis of mouse corneal infections by Pseudomonas aeruginosa. When the parental strain PAO1 was cultured in high-iron medium (5 micrograms of Fe per ml), it was less virulent than when it was cultured in low-iron medium (0.05 microgram of Fe per ml). The iron concentration of the growth medium had no effect on the virulence of a P. aeruginosa mutant which was resistant to the iron regulation of toxin A yields (PAO-toxFeR-18). A severely defective iron transport mutant, PAO-toxFeR-10, was avirulent regardless of the iron concentration of the growth medium. These studies indicate that both iron acquisition and iron regulation of toxin production are important factors in the determination of P. aeruginosa virulence.
The effectiveness of netilmicin was evaluated retrospectively in 40 patients with culture-documented bacteremia due to Pseudomonas aeruginosa. Netilmicin was the only antibiotic active in vitro against P aeruginosa that was administered to these patients. In 18 patients, Pseudomonas bacteremia developed in association with a Pseudomonas infection of the urinary tract; in 22 patients, Pseudomonas bacteremia developed from nonurinary or unknown sources. A clinical resolution or improvement was observed in 92% of the evaluable patients, and P aeruginosa was eliminated from the blood of 90% of the patients. The drug had nephrotoxic effects in two patients, but in no patient was there subjective or audiometric evidence of ototoxic effects. Three patients died during therapy. Based on these data, netilmicin is effective, and is associated with a low incidence of toxic effects, in the treatment of patients with Pseudomonas bacteremia.
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During the 19-month study period, 48 (2 per cent) of the 2177 neonates admitted to the neonatal intensive care unit (NICU) yielded Pseudomonas aeruginosa growths in blood cultures. All these neonates had clinical and haematological evidences of sepsis. Prominent clinical features included sclerema, violaceus necrotic patches, necrotizing enterocolitis (NEC), conjugated hyperbilirubinaemia, and DIC. Over all mortality was 23 per cent, distinctly higher in premature neonates with RDS. The mean gestational age and birth weights (+/- SD) of these neonates were 36.42 (+/- 2.73) weeks and 2173.34 (+/- 567.33) g, respectively. Approximately half of the total cases had low birth weight. Other adverse perinatal events before the development of sepsis included birth asphyxia (60 per cent), neonatal resuscitation (67 per cent), meconium aspiration syndrome (29 per cent), hyaline membrane disease (8 per cent), prolonged hospitalization (44 per cent), closed incubator care (17 per cent), prolonged intravenous fluids (42 per cent), repeated blood sampling (63 per cent), and umbilical catheterization (4 per cent). Analysis of the trend of Pseudomonas sepsis in our NICU revealed six definite outbreaks (more than two cases) interspersed with occasional (one or two) cases. Six study months, however, remained free of Pseudomonas sepsis. Index case was demonstrable on seven occasions. Bacteriological surveillance of the NICU after onset of initial case/cases revealed statistically significant colonization of resuscitation equipment, baby placement sites, and various cleansing solutions by the same bacterial species (P < 0.05). It is possible that Pseudomonas was introduced to our NICU from transfer admissions from other hospitals since on four occasions index case was the one transferred from outside.(ABSTRACT TRUNCATED AT 250 WORDS)
Pseudomonas aeruginosa has emerged as an important pathogen during the past two decades. It causes between 10% and 20% of infections in most hospitals. Pseudomonas infection is especially prevalent among patients with burn wounds, cystic fibrosis, acute leukemia, organ transplants, and intravenous-drug addiction. P. aeruginosa is a common nosocomial contaminant, and epidemics have been traced to many items in the hospital environment. Patients who are hospitalized for extended periods are frequently colonized by this organism and are at increased risk of developing infection. The most serious infections include malignant external otitis, endophthalmitis, endocarditis, meningitis, pneumonia, and septicemia. The likelihood of recovery from pseudomonas infection is related to the severity of the patient's underlying disease process. The introduction of the antipseudomonal aminoglycosides and penicillins has improved substantially the prognosis of these infections. Ticarcillin and carbenicillin have been especially beneficial in neutropenic patients; however, prompt institution of therapy is mandatory for optimal benefit. Many new drugs with antipseudomonal activity, including penicillins, cephalosporins, and other beta-lactams, have been introduced in recent years and offer the potential for new approaches to therapy for these infections.
The perinatal histories and hospital courses of all neonates born at Grady Memorial Hospital who developed Pseudomonas aeruginosa sepsis or meningitis in the 5-year period 1989-1993 were reviewed. In addition a case-control study was performed to evaluate selected risk factors for this infection. Twenty-one patients had one or more blood cultures positive for P. aeruginosa. An additional patient had P. aeruginosa meningitis without bacteremia. All infections occurred after 5 days of age. The overall incidence of P. aeruginosa infection was 0.7/1000 live births. All cases occurred in infants < 1500 g at birth, for a birth weight-specific rate of 19.5/1000 livebirths in this weight class. Clinical manifestations of disease did not distinguish P. aeruginosa from other causes of fulminant neonatal sepsis. Fifty percent of cases died. Mortality was inversely related to postnatal age at diagnosis. The 22 cases were compared with 44 controls matched for birth weight, gestational age, sex, duration of hospital stay and admission date. Cases were more likely than controls to have a history of feeding intolerance, interrupted enteral intake and prolonged parenteral hyperalimentation. Case infants received intravenous antibiotics for a significantly longer period of time than did controls. There was an association between P. aeruginosa sepsis and necrotizing enterocolitis (36% cases vs. 7% of controls had prior or concurrent necrotizing enterocolitis, P < 0.01). In summary P. aeruginosa sepsis is primarily a late onset nosocomial infection in very low birth weight infants. The case fatality rate of 50% in this series emphasizes its continued importance.
CONTEXT: Sporadic infections following ear piercing are well documented, but common-source outbreaks are rarely recognized. OBJECTIVE: To investigate reports of auricular chondritis subsequent to commercial ear piercing. DESIGN, SETTING, AND SUBJECTS: Outbreak investigation by Oregon public health agencies, including cohort study of persons pierced at a jewelry kiosk in August-September 2000, environmental sampling, and molecular subtyping of isolates. Confirmed cases had Pseudomonas aeruginosa cultured from ear wounds. Suspected cases had signs and symptoms of external ear infection, including drainage of pus or blood for at least 14 days. MAIN OUTCOME MEASURES: Risk factors for infection and comparison of bacterial isolates by molecular subtyping. RESULTS: From 186 piercings in 118 individuals, we identified 7 confirmed P aeruginosa infections and 18 suspected infections. Confirmed cases were 10 to 19 years old. Most were initially treated with antibiotics ineffective against Pseudomonas. Four were hospitalized, 4 underwent incision and drainage surgeries (1 as an outpatient), and several were cosmetically deformed. Upper ear cartilage piercing was more likely to result in either confirmed or suspected infection than was lobe piercing (confirmed: RR undefined, P<.001; suspected: RR, 3.6; 95% confidence interval, 1.5-8.5). All persons with confirmed infections had their ear cartilage pierced with an open, spring-loaded piercing gun. Patient isolates were indistinguishable by molecular subtyping, and matching isolates were recovered from a disinfectant bottle and nearby sink. At least 1 worker admitted sometimes spraying the disinfectant on the ear studs before piercing. CONCLUSIONS: Ear cartilage piercing is inherently more risky than lobe piercing. Clinicians should respond aggressively to potential auricular chondritis and consider Pseudomonas a possible cause pending culture results.
Cystic fibrosis (CF) is the most common genetic disease of Caucasians and also the most important lung disease of the first decades of life associated with infections by a variety of bacteria species especially Pseudomonas aeruginosa and Staphylococcus aureus. During the last two decades chronic Pseudomonas infection has emerged as the most difficult problem. Pseudomonas bacteria are able to synthesize numerous extracellular factors (virulence factors) contributing to its pathogenicity. Immunological defense mechanisms against Pseudomonas (and other bacteria species) have been demonstrated, but a complete elimination from infected lungs has not been observed. Therapy of Pseudomonas infections includes frequently combinations of antibiotics of the beta-lactam and aminoglycoside type.
Extensive immunohistochemical and thin-layer chromatogram-immunostain analyses were carried out to establish whether asialo GM1, a glycolipid which contains binding sites for Pseudomonas aeruginosa, is present in corneal epithelium. The data suggest that rabbit corneal epithelium does not contain detectable levels of asialo GM1 even after corneas are scarified and incubated with trypsin, P. aeruginosa, or P. aeruginosa exoproducts to expose potential cryptic sites. Preliminary immunohistochemical analyses indicated that asialo GM1 is also not found in human corneas.
Pseudomonas aeruginosa infection is unusual in individuals with human immunodeficiency virus infection, and it most often occurs in the setting of other risk factors, such as neutropenia or cytotoxic drug use. We noted an increasing number of pulmonary isolates of this organism in our clinic population and sought to describe the clinical correlates of this finding. Our study consisted of a retrospective review of the microbiology, radiology, and clinical records of 1,852 HIV-seropositive adults seen at a university-based outpatient AIDS clinic. We identified 16 individuals with Pseudomonas bronchopulmonary infection. All subjects had advanced HIV disease with prior AIDS diagnoses, and mean CD4 counts of 25/mm3 (0.025 x 10(9)/L). Pseudomonas was the sole pulmonary pathogen in 14 of 16 patients and was associated with new chest X-ray abnormalities in 14 cases. Four individuals had acute pseudomonal pneumonia with sepsis; this presentation was associated with hospitalization and other known risk factors for Pseudomonas infection. In contrast, 12 patients had more indolent, community-acquired infection, which had a low mortality rate and occurred in the absence of other risk factors. Survivors of the initial bout of Pseudomonas infection had an 86% relapse rate despite a median survival of only 4.5 months. This pattern of pseudomonal disease is reminiscent of cystic fibrosis and suggests a role for maintenance therapy.
Infection of Pseudomonas BAL-31 with the lipid-containing bacteriophage PM2 resulted in no detectable change in the rate of phosphatidylglycerol (PG) or phosphatidylethanolamine (PE) biosynthesis. An increase in the PG content of infected cultures was not seen until the cultures began to lyse, and this increase was in fact only a relative increase resulting from the extensive turnover of PE at the onset of culture lysis. Turnover studies revealed that the glycerol, phosphorus fatty acid, and ethanolamine moieties of PE turned over simultaneously at the time of lysis, and therefore made it unlikely that there was a PE to PG conversion during the latent period of the phage. The lipid found in the bacteriophage did not reflect a preferential selection for lipid synthesized before or after infection, but in fact reflected the composition of the host membrane at the time the phage were assembled. The use of a modified medium that allowed the cultivation of Pseudomonas BAL-31 as a prototroph and resulted in reliable lysis times of infected cultures led us to the conclusion that PM2 infection effects little change in host phospholipid metabolism, and that there is sufficient PG in the host cytoplasmic membrane to account for a full burst of phage. As a result of the reliable lysis times that we have achieved, we concluded that certain metabolic events, i.e., PE turnover, are lytic phenomena and must not be confused with events relevant to the biosynthesis and maturation of the phage.
The effect of Pseudomonas aeruginosa infection on contact sensitivity to 2-phenyl-4-ethoximethylene-oxazolone (oxazolone) and on antibody response to sheep erythrocytes, horse erythrocytes, and Escherichia coli 0111:B4 lipopolysacharide was investigated in outbred C57BL/6 mice. Injection of 0.5 and 0.2 median lethal doses significantly depressed contact sensitivity to oxazolone, whereas injection of 0.5 median lethal dose of heat-killed microorganisms did not. The filtrate of a 24-h broth culture did not affect contact sensitivity as well. Antibody production against sheep erythrocytes, horse erythrocytes, and lipopolysaccharide (evaluated as plaque-forming cells and circulating hemagglutinin and hemolysin titers) was found to be significantly enhanced both in animals injected with living bacteria and in those which received heat-killed microorganisms. The simultaneous occurrence of depression of cell-mediated immunity and potentiation of humoral response suggests that P. aeruginosa might interfere at different levels of the host immunological responsiveness.
The route of bacterial infection of the lower respiratory tract is generally one of descent subsequent to colonisation of the oral and oropharyngeal mucosa. The interaction between Pseudomonas aeruginosa (wild type) and the bronchial epithelium was studied in bronchial mucosal probes cultured in tissue culture medium. It was possible to demonstrate that, even after loss of the mucus layer, adherence between the bacteria and the bronchial epithelium does not take place if ciliary function remains intact. Only after mechanical destruction of the bronchial epithelium, in proximity to squamous metaplasia or after loss or malfunction of the cilia of the bronchial epithelial cells was adhesion between bacteria and bronchial epithelial cells or basement membrane demonstrated by electron microscopy. After loss of the cilia following adenovirus-infection, adhesion between P. aeruginosa and the bronchial epithelial cells was visible. These results indicate that ciliary function must be of crucial significance in bacterial epithelial colonisation.
Carbenicillin and ticarcillin are penicillins which were initially developed as agents to treat serious Pseudomonas infections in the seriously ill hospitalized patient. These drugs have made a major contribution to improved survival in the neutropenic patients with Pseudomonas infection, the burn patient and to the care of the patient with cystic fibrosis. Areas of use for the compounds have enlarged to include aspiration pneumonitis in hospitalized patients, intra-abdominal and pelvic sepsis, and infections due to Proteus and Enterobacter species. Careful attention to the pharmacology of the agents is necessary to achieve clinical and bacteriologic success and to avoid the toxic side-effects such as bleeding and hypokalemia associated with the use of these agents. A decade of use has shown that the agents have remained effective agents in institutions in which their use has not been abused. It is too early to clearly position azlocillin, mezlocillin, and piperacillin. In the next few years the role of these potent compounds will be established. As noted in this review, these three agents have been used with success to treat all of the aforementioned infections. With these drugs it is also essential that the physician closely correlate in vitro data and the human pharmacology of the drugs if he or she wishes to achieve the most effective response from the agents.
Purinergic receptors are expressed throughout the respiratory system in diverse cell types. The efficiency of mucus clearance in the airways, the cascade leading to tissue injury, and inflammation are modulated by autocrine/paracrine release of nucleotides and signaling by purinergic receptors. We assessed the role of purinergic receptors in innate host defense of the lung in vivo by infecting mice deficient in P2Y1, P2Y2, or both receptors with intratracheal instillation of Pseudomonas aeruginosa. After P. aeruginosa challenge, all double knockout (P2Y1/P2Y2-/-) mice succumbed within 30 h of challenge, whereas 85% of the wild-type mice survived. Thirty-three percent of wild-type mice survived beyond 96 h. Single knockout mice, P2Y1-/-, or P2Y2-/-, exhibited intermediate survivals. Twenty-four hours following intratracheal instillation of a sublethal dose of P. aeruginosa, the level of total protein in bronchoalveolar lavage fluid was 1.8-fold higher in double knockout than in wild-type mice (P < 0.04). Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y1/P2Y2-/- mice relative to wild-type mice. These findings suggest that purinergic receptors exert a protective role against infection of the lungs by P. aeruginosa by decreasing protein leak and enhancing proinflammatory cytokine response.