Cefamandole treatment of pulmonary infection caused by gram-negative rods.
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Biomedical subjects
Publications and source records attributed to M A Sande.
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The emergence of Providencia stuartii as a hospital pathogen in a burn unit was demonstrated by routine infection surveillance. The organism was initially recognized in a burn wound and subsequently in urine or sputum. Compared to controls, those patients harboring P. stuartii were similar in age and percentage of body surface burned and were more likely to have been in one of the two burn unit rooms, (p less than 0.02). Infection with P. stuartii was independent of duration in the Intensive Care Unit or Burn Unit, and of number of visits to hydrotherapy or operating rooms (OR). Once patients were colonized with P. stuartii they had greater morbidity than non-colonized patients as evidenced by longer stays in the unit and increased visits to the OR for debridement. P. stuartii was isolated from air samples (5/14) more commonly than from the hands of personnel. In vitro tests suggested that extensive use of parenteral gentamicin and replacement of the antibacterial topical cream sulfamylon by silver sulfadiazine favored the emergence of P. stuartii over Pseudomonas aeruginosa as the predominant colonizing organism.
Two macrolide antibiotics, josamycin and erythromycin stearate, were administered orally to healthy, adult male volunteers for a comparative study of their pharmacological properties. In comparable doses, josamycin and erythromycin produced similar plasma concentrations, with similar half-lives and elimination constants. An initial loading dose of 1.5 g of josamycin produced greater peak concentrations of antibiotic throughout a 10-day period with a regimen of every 6 h. In addition, josamycin tended to reach higher peak and trough concentrations after regimens of every 6 or 8 h were maintained for 2 days. Josamycin penetrated into saliva, sweat, and tears, and it was better tolerated in fasting subjects than was erythromycin stearate.
The in vitro activity of josamycin and erythromycin against five bacterial species was compared. In general, erythromycin was slightly more active by weight than josamycin, although both agents had a similar range of activity.
A method of disinfecting the bronchofiberscope that requires 5 minutes was tested against Mycobacterium tuberculosis, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans, influenza virus, and rhinovirus. The bronchofiberscope was contaminated with either sputum or mucin containing the microorganism. Disinfection was performed by washing the inner channel and the outer sheath with a hexachlorophene detergent followed by a solution containing povidone-iodine, ethanol, and water. A total of 76 specimens was tested; all postdisinfection cultures were sterile with the exception of one containing less than 102 colonies per ml of S. aureus.
The bactericidal rate of nafcillin and the combination of nafcillin and gentamicin against Staphylococcus aureus were compared in vitro and in experimental endocarditis. The combination proved synergistic against 8 strains of S. aureus in broth. In rabbits with S. aureus endocarditis, the organism was eradicated more rapidly from cardiac vegetations when animals were treated with the combination than with nafcillin alone. Gentamicin alone was ineffective. This combination is under study in the therapy of acute endocarditis caused by penicillinase-producing S. aureus.
Twenty-four adults with clinical evidence of sinusitis were studied by 65 needle punctures of the maxillary antrum. Fourteen of 15 sinuses with normal transillumination and 19 of 26 that were dull had normal aspirates, whereas 24 of 24 that were opaque had abnormal aspirates (P less than 0.001). Marked mucosal thickening as determined radiologically (Water's view) was associated with abnormal aspirates whereas lesser mucosal thickening was not (P less than 0.001). In acute sinusitis, there was a strong correlation between high aspirate leukocyte counts (greater than 1000 per cubic millimeter) and infection as manifested by bacterial titers of greater than 10(5) per milliliter or the isolation of virus fungus (P greater than 0.001). Anterior-nasal-swab cultures correlated poorly with direct aspirate culters. Organisms frequently recovered from the sinus included Haemophilus influenzae, Strepto coccus pneumoniae, and anaerobic bacteria. Rhinovirus was recovered twice. Antibiotics were usedful in patients with acute sinusitis if the organism was sensitive in vitro (P less than 0.001).
The cause of pediatric diarrhea in Brazil was investigated with use of assays for toxigenic and invasive bacteria. Potential etiologic agents were identified in 31 of 40 consecutive children with diarrhea: toxigenic Escherichia coli or klebsiella in 20 patients (50 per cent); invasive Esch, coli or salmonella in four (10 per cent), and both toxigenic and invasive organisms in seven (18 per cent). Fecal leukocytes were present in nine of the 11 patients (82 per cent) with invasive pathogens. All 27 patients with toxigenic isolates had organisms that produced heat-labile cholera-like toxin; three patients had Esch. coli that also produced a heat-stable toxin. Among 20 controls without diarrhea there were no organisms that produced heat-labile toxin or tissue invasion, but there was one Esch. coli that produced only heat-stable toxin and one salmonella. In this pediatric population Esch. coli appears to cause most acute diarrheas due to toxigenic and invasive pathogenic mechanisms.
A patient with hydrocephalus and a ventriculojugular shunt presented with acute nephritis, nephrotic syndrome (proteinuria 10 g/24 hours), decreased complement levels, circulating immune complexes and diminished creatinine clearance (41 ml/min). Seven blood cultures grew Corynebacterium bovis. A renal biopsy specimen revealed mesangiocapillary glomerulonephritis by light microscopy, and thickened glomerular basement membranes with areas of increased granular density by electron microscopy. Immunofluorescent examination of the biopsy specimen demonstrated 2+ granular glomerular basement membrane deposits of immunoglobulin M (IgM), with trace third component of complement (C-3), fourth component of complement (C-4) and immunoglobulin G (IgG). Rabbits immunized with C. bovis produced a line of partial identity in agar with patient serum against a sonicate of C. bovis. Indirect fluorescein staining of the biopsy specimen with the rabbit antiserum demonstrated 1+ granular glomerular basement membrane deposits. Potassium thiocyanate microelution of sections prior to examination markedly diminished staining with antihuman antiserum, but did not affect staining with rabbit antiserum. Following initial therapy with intravenous penicillin for six weeks the bacteremia cleared, serum complement levels returned to normal, proteinuria decreased and creatinine clearance increased. A relapse occured four weeks later with decreased complement levels, increased proteinuria and decreased creatinine clearance. Blood cultures were again positive for C. bovis. Following therapy with erythromycin and rifampin, the bacteremia cleared and there was a sustained improvement of all parameters. To our knowledge, this is the first time an association has been noted between C. bovis ventriculojugular shunt infection and glomerulonephritis. These findings support the potential role of C. bovis as an etiologic agent in human renal disease and further define the immune complex nature of shunt nephritis.
The rate at which various antimicrobial agents eradicated Staphylococcus aureus from cardiac vegetations in a rabbit model of endocarditis was studied. The rate at which various drugs and combinations killed high titers of bacteria in broth correlated with the relative effectiveness of the agents in vivo. Gentamicin plus penicillin proved to be synergistic in vitro and more effective in eradicating bacteria from cardiac vegetations in vivo than was penicillin alone. Vancomycin killed bacteria at a rate similar to that for the combination of penicillin and gentamicin, and the rate for cefazolin was similar to that for penicillin alone. Clindamycin was less effective in vivo and in vitro than penicillin. Therapy with rifampin led to the emergence of resistant organisms, and, when penicillin, this drug was less effective in vitro and in vivo than was penicillin alone. This model appears to offer an effective method for evaluation of antimicrobial treatment of staphylococcal endocarditis.
The mechanisms by which Streptococcus pneumoniae spreads from person to person are poorly understood. In this study, optimal methods for sampling, isolation, and identification of S. pneumoniae from healthy carriers were investigated. Factors influencing carriage rates were analyzed. Findings included the importance of pharyngeal rather than of nasal sampling in adults, the greater sensitivity of mouse inoculation compared with direct streaking of blood agar plates, and the superiority of the Quellung reaction with omniserum over the optochin disk as a means of identification of S. pneumoniae. Carriage rates were highest in children of preschool (35%) or grammar school (29%) age and in adults with preschool children in the family (18%). Rates were lowest in adults without preschool children in the family (2%-9%).
Factors that affect the spread of Streptococcus pneumoniae and the antibody responses associated with colonization were studied in 64 families for periods of eight to 52 weeks. Surveillance included daily recording of respiratory symptoms and bimonthly pharyngeal cultures for identification of the pneumococcal carrier state. Rhinovirus cultures were included for a portion of the study period. Intrafamilial carriage of a single type of S. pneumoniae and simultaneous spread to more than one family member were commonmspread often occurred in association with an upper respiratory tract infection; simultaneous transmission of S. pneumoniae and a rhinovirus was documented. Preexisting, type-specific serum antibody did not prevent acquisition of homotypic S. pneumoniae but did appear to shorten the duration of pharyngeal carriage. Sera of all 11 adults had greater than 150 ng of antibody nitrogen/ml of homotypic serum antibody (measured by a radioimmunoassay) before colonization. In contrast, only one of 13 preschool children had homotypic antibody concentrations of this magnitude before colonization. A threefold or greater rise in the concentration of homotypic antibody occurred in 13 of 24 children (54%) after acquisition of S. pneumoniae; the increase in antibody concentration was associated with illness in six of the children. On the other hand, acquisition of S. pneumoniae in adults was not associated with an increase in concentration of homotypic serum antibody.
In a prospective study from May 1971 to November 1973, 20 consecutive patients with a diagnosis of disseminated cryptococcosis were treated for six weeks with a combination of amphotericin B (20 mg daily) intravenously and flucytosine (150 mg/kg daily) orally. Fifteen patients has culturally docummented Cryptococcus neoformans meningitis, and three died of infection early in therapy. Of the remaining 12 patients, eight were alive and well eight to 34 months after therapy, and four died of other causes. None of the surviving patients has relapsed. Hematologic complications developed in nine patients, three of whom had no underlying lymphoreticular disorder or therapy with known cytotoxic agents. Renal insufficiency of mild degree occurred in only six patients. A shorter period of hospitalization and reduction in toxicity of amphotericin B suggest that combined therapy is a safe and efficacious alternative to other regimens.
Rabits with Streptococcus viridans aortic valve endocarditis develop anaemia and reticulocytosis which increase with the duration of infection. Mean red cell counts decreased from 6.05 +/- 0.29 X 10(6) per mul before infection to 4.10 +/- 0.18 X 10(6) per mul after 11 to 20 days of endocarditis and reticulocytes increased from 1.16 +/- 0.14 X 10(5) per mul to 4.91 +/- 0.83 X 10(5) per mul after more than 20 days of endocarditis. The anaemia could not be explained by intravascular haemolysis. Anti-erythrocyte antibodies were not detected. Splenomegaly was a consistent finding and also increased with the duration of infection. Red cell half life (T1/2) was shortened to 4.7 +/- 0.3 days in rabbits with endocarditis compared with normal T1/2 of 11.1 +/- 0.5 days. The T1/2 of red cells from infected animals was prolonged when measured in noninfected rabbits and splenectomized animals had a mean red cell T1/2 of 9.25 days after three weeks of infection. These studies suggest that splenic enlargement associated with infection results in red cell sequestration, a mechanism not well recognized as contributing to the anaemia of endocarditis.
Initial studies indicate that rifampin may be useful for the treatment of Staphylococcus aureus infections. Because bacterial resistance to rifampin may develop rapidly, its widespread use could result in the emergence of a resistant flora. This study evaluates the effectiveness of rifampin in reducing the nasal carriage of S. aureus and the rate at which resistant mutants emerge in a tuberculosis hospital where the drug was widely used. Anterior nares cultures were performed four times over a 13-month period. Carriage rates of S. aureus were 1.7% in 227 patients receiving rifampin, 7.8% in 190 patients receiving other antituberculous therapy, and 14.2% in 98 hospital employees (rifampin-treated versus other patients, P < 0.003; rifampin-treated versus employees, P < 0.001; employees versus other patients, P = 0.157). All four strains of S. aureus isolated from patients on rifampin therapy were rifampin resistant. All 16 strains isolated from patients not on rifampin and 15 of 16 strains isolated from hospital personnel were susceptible. One instance of apparent spread of a rifampin-resistant organism occurred in a hospital attendant who had never received rifampin.
The successful therapy of enterococcal endocarditis requires prolonged administration of synergistic antibiotic combinations. Controversy has arisen regarding optimal therapy (i) when the organism possesses high-level streptomycin resistance, and (ii) when the patient is allergic to penicillin. This study examines these questions in vitro and in a rabbit model of enterococcal endocarditis. The combination of penicillin with either streptomycin or gentamicin increased the rate of bacterial killing in vitro and in vivo when compared with penicillin alone (P < 0.05) when the test strain was relatively susceptible to streptomycin (minimal inhibitory concentration, 128 mug/ml). Only the combination of penicillin and gentamicin was consistently more effective than penicillin alone (P < 0.01) when the test strain was highly resistant to streptomycin (minimal inhibitory concentration > 150,000 mug/ml). The combination of vancomycin and streptomycin was more rapidly bactericidal than vancomycin alone in vitro and in the animal model against the streptomycin-susceptible strain (P < 0.01). The relative rate of in vitro bacterial killing by various antibiotics and combinations was predictive of the efficacy of these drugs in eradicating enterococci from cardiac vegetation in experimental endocarditis.
Simple methods to enhance the detection of pneumococci in respiratory secretions are needed. Sheep blood agar containing 5 mug of gentamicin per ml was more often positive (89%) than either standard sheep blood agar (54%) or mouse inoculation (65%) in recovering pneumococci from 62 adult and pediatric patients. In adults, the direct quellung test on sputum smear was a rapid, sensitive method for predicting subsequent pneumococcal isolation by culture (19 of 20 patients, 95%). The quellung test and gentamicin plate show improved sensitivity over current techniques for pneumococcal detection and can be recommended for general use.