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Biomedical subjects

D A Goldmann

Publications and source records attributed to D A Goldmann.

At least 109 records · Page 6Linked to original sources

Nosocomial infection and death in a neonatal intensive care unit.

Based on five years of prospective surveillance in a neonatal intensive care unit (NICU), the association of nosocomial infection with death during hospitalization was studied. Low birth weight and patent ductus arteriosus (PDA) were the variables most strongly associated with nosocomial infection. After stratification for these variables, there was a persistent association between nosocomial infection and increased risk of death (relative risk = 1.96; 95% confidence interval, 1.09-4.44; P = 0.03). The relative risk of mortality with nosocomial infection was significantly modified (P = 0.02) by the presence of PDA (relative risk = 3.42; 95% confidence interval, 1.68-6.95 for infants without PDA; no effect for infants with PDA). Relocation of the NICU to an improved, better-staffed facility was associated with a significant decrease in the adjusted nosocomial infection rate (relative risk [old NICU/new NICU] = 9.73; 95% confidence interval, 4.30-22.0). This improvement was accompanied by a statistically insignificant reduction in the overall mortality because other causes of death, such as low birth weight and serious underlying disease, are much more common in this population and thus are more important determinants of outcome.

Boston↗

The role of pili and capsule in the pathogenesis of neonatal infection with Escherichia coli K1.

The role of pili and capsule was studied in neonatal infection with Escherichia coli K1. E coli strains were selectively cultured into three phases: mannose-sensitive (MS) piliated, non-mannose-sensitive (NMS) piliated, and nonpiliated. A high percentage of neonatal rats fed each phase of K1 strains developed bacteremia; there was no bacteremia with non-K1 strains or an acapsular mutant of K1 strain C94 (C94K-). Oral cavity colonization was noted in nearly 100% of rats fed K1 strains, non-K1 strains, or C94K-, regardless of the phase of piliation at feeding. Only MS piliated bacteria were found on oral cavity culture, indicating a rapid shift of NMS piliated and nonpiliated bacteria to the MS piliated phase. Conversely, only nonpiliated bacteria were found on blood culture when neonatal rats were fed piliated bacteria. Colonization of ileal epithelium was not observed. Thus, in vivo phase variation may be important in colonization and bacteremia with E coli K1.

Adhesiveness↗

Randomized, double-blind evaluation of azlocillin for the treatment of pulmonary exacerbations of cystic fibrosis.

Patients with cystic fibrosis hospitalized because of deterioration in their pulmonary disease were randomly assigned to receive ten days of intravenous antibiotic therapy with either ticarcillin plus tobramycin (previously the standard regimen at our hospital), azlocillin plus tobramycin or azlocillin plus placebo. Pulmonary function and microbiological responses were similar in the three treatment groups, although patients receiving azlocillin and placebo tended to have a smaller reduction in the concentration of bacteria in the sputum and a greater rate of acquisition of antibiotic-resistant organisms. Overall, in-hospital treatment was associated with a significant improvement in Shwachman score, pulmonary function tests, and PO2. Improvement was noted by day 5 of therapy, continued through day 10, and was partially maintained at follow-up clinic visit one month after discharge. There was also a statistically significant reduction in sputum bacterial concentration, but patients cultured at the conclusion of antibiotic therapy still had a mean of 10(7) cfu/ml in sputum. Pseudomonas aeruginosa, the principal pathogen recovered from sputum cultures in this study, was transiently suppressed to sub-detectable levels in only one patient. There was no correlation between microbiological response and change in any parameter of pulmonary function. By follow-up clinic visit, sputum bacteria had returned to pre-treatment levels, and antibiotic-resistant organisms persisted in all patients from whom they had been recovered during hospitalization.

Adolescent↗

In vitro activity of rifampin in combination with oxacillin against Staphylococcus aureus.

The in vitro activity of rifampin alone and in combination with oxacillin was determined for 75 Staphylococcus aureus strains (64 susceptible and 11 resistant to oxacillin). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined by broth microdilution; antibiotic combinations were evaluated by microdilution checkerboard and time-kill studies. The 90% MIC of rifampin was less than or equal to 0.015 micrograms/ml after both 24 and 48 h of incubation. The 90% MBC of rifampin was less than or equal to 2.0 micrograms/ml on subculture at 24 h of incubation and less than or equal to 0.5 micrograms/ml on subculture at 48 h. MIC checkerboards with oxacillin-susceptible strains revealed an additive or indifferent effect in 35 strains (55%) and antagonism in 29 strains (45%). MBC checkerboards performed by subculture at 24 h demonstrated antagonism for all but one of the oxacillin-susceptible strains, with sub-MBCs of rifampin impairing the bactericidal activity of oxacillin. MBC checkerboards performed by 48-h subculture revealed antagonism with 37 strains (58%); in 26 additional strains (40%), a synergistic, additive, or indifferent effect was observed at low antibiotic concentrations, but antagonism was seen at higher concentrations. Time-kill studies tended to show indifference rather than antagonism with oxacillin plus rifampin. In checkerboards performed with oxacillin-resistant strains, the addition of rifampin did not improve oxacillin inhibitory or bactericidal activity to a clinically significant extent; however, the addition of oxacillin improved the bactericidal activity of rifampin at easily achievable serum concentrations.

Drug Interactions↗

Trimethoprim and rifampin in combination for chemoprophylaxis of household contacts of patients with invasive infections due to Haemophilus influenzae type b.

We compared the effectiveness of rifampin-trimethoprim in fixed combination (3.75:1) to rifampin alone in the eradication of Haemophilus influenzae type b carriage among contacts of patients with invasive infection caused by this organism. The study population was composed of 127 index patients and 620 contacts. Twenty-six percent of contacts were colonized. Rifampin-trimethoprim eradicated carriage in 77.6% of contacts (71.1% in contacts less than 5 years, 84.2% in contacts greater than or equal to 5 years) whereas rifampin eradicated carriage in 69.9% of contacts (56.4% in contacts less than 5 years, 81.8% in contacts greater than or equal to 5 years). A single isolate resistant to rifampin and rifampin-trimethoprim was encountered. The eradication rate achieved with this regimen of rifampin-trimethoprim was too low to recommend its routine use. However, a higher dose or longer course might merit clinical trial.

Carrier State↗

Moxalactam pharmacokinetics in children.

We measured the serum concentrations of moxalactam in 10 children receiving antibiotic prophylaxis for surgery and in 18 children treated for documented or suspected infections. Moxalactam was administered intravenously at a dose of 50 mg/kg every 8 h. After the first dose in 28 patients, mean moxalactam concentrations 5 min, 30 min, 2 h, and 8 h after infusion were 257, 177, 82.2, and 17.5 micrograms/ml, respectively. The mean half-life (T 1/2) was 2.44 h (range: 0.55 to 7.96 h). The mean distribution volume (VD) was 0.30 liters per kg. No significant accumulation was observed with multiple doses. Prophylactic and therapeutic groups had similar serum levels, T 1/2, and VD. The five infants less than 1 year of age had a lower mean 30-min level (P less than 0.01), larger VD (P less than 0.001) and longer T 1/2 (P less than 0.025) than the children older than 1 year. A dose of 50 mg/kg produced 30-min levels in excess of 64 microgram/ml in all patients studied, but 8-h trough levels were below the minimal inhibitory concentrations breakpoint of 17 mg/ml in 32% of patients.

Adolescent↗

Improved antibiotic usage following introduction of a novel prescription system.

We investigated the impact of a novel antibiotic prescription system on antibiotic use. After a two-month baseline monitoring period, an antibiotic prescription form was introduced on surgical and medical wards, which obliged physicians to categorize antibiotic use as prophylactic, empirical (culture results unavailable), or therapeutic. Depending on the category, administration of antibiotics was automatically discontinued after two days (prophylactic), three days (empirical), or seven days (therapeutic) unless the physician renewed the order or specified an alternate duration of administration. In the subsequent two-month intervention period, 233 (60%) of 390 surgical patients received prophylactic antibiotics compared with 281 (68%) of 413 in the baseline period. Mean duration of prophylaxis was reduced from 4.9 +/- 2.4 days to 2.9 +/- 1.6 days. In the intervention period, 11% of patients received their first prophylactic dose postoperatively, compared with a 30% baseline rate. The percentage of urology patients receiving appropriate therapy for urinary tract infection increased from 38% to 89%. No significant changes in antibiotic use were noted on the medical service. This antibiotic prescription system may have a substantial impact on antibiotic use.

Adult↗

Mucoid Escherichia coli in cystic fibrosis.

Patients with cystic fibrosis commonly harbor in their lungs strains of Pseudomonas aeruginosa that have a mucoid coating considered virtually pathognomonic for the disease. We found that strains of Escherichia coli with a morphologically similar mucoid coating were present in the respiratory tracts of eight (11.8 per cent) of 68 patients with cystic fibrosis whose sputum cultures yielded Esch. coli, as compared with none of 89 patients without cystic fibrosis who had Esch. coli in sputum. Mucoid strains of Esch. coli were also recovered from the stools of five (11.1 per cent) of 45 patients with cystic fibrosis, as compared with one (0.7 per cent) of 150 patients without cystic fibrosis. The mucoid substances purified from Esch. coli were biochemically and antigenically distinct from those of P. aeruginosa. We conclude that the respiratory tract in cystic fibrosis offers an environment conducive to the production of a mucoid coating not only by P. aeruginosa but by other gram-negative bacilli as well.

Bacteriological Techniques↗

Complications of intravenous therapy with steel needles and Teflon catheters. A comparative study.

Complications of intravenous therapy with steel needles and small-bore Teflon catheters were compared in a randomized study of 954 cannula insertions. Cannulas were inserted and cared for by an intravenous team following a standard protocol. There were no cases of cannula-related septicemia and only one case of local infection, a cellulitis in the group in which Teflon catheters were used. There was a low incidence of positive semiquantitative cannula cultures in both treatment groups (steel needles 1.5 percent, Teflon catheters 1.4 percent). The risk of phlebitis was significantly greater with Teflon catheters (18.8 percent with Teflon catheters, 8.8 percent with steel needles, adjusted odds ratio 1.87). Steel needles were significantly associated with infiltration (17.9 percent with Teflon catheters, 40.1 percent with steel needles, adjusted odds ratio 0.39). The over-all rate of complications was significantly greater for the group in which steel needles were used (53.8 versus 64.0 percent, adjusted odds ratio 0.72), principally due to the increased risk of infiltration with steel needles. Analysis of the per day risk of infiltration and phlebitis revealed that these relationships were present for each day the cannulas remained in place. We conclude (1) that steel needles and small-bore Teflon catheters can both be used with low risk of infection and (2) that Teflon catheters more frequently cause phlebitis, whereas steel needles infiltrate more readily.

Adolescent↗

Rifampin chemoprophylaxis for household contacts of patients with invasive infections due to Haemophilus influenzae type b.

To determine the efficacy of rifampin chemoprophylaxis in eradication of oropharyngeal carriage of Haemophilus influenzae type b, we conducted a multicenter, double-blind, placebo-controlled trial among household contacts of patients hospitalized for invasive HIB infection. Seventy-nine index patients and 400 close contacts were studied; 26.5% of contacts were colonized. The efficacy of rifampin (10 mg/kg/dose, 600 mg/dose maximum, twice daily for two days) in eradicating carriage was 52% and varied with age (75.6% in persons greater than or equal to 5 and 27% in those less than 5 years). Eradication rates in those less than 5 years were not significantly better than for placebo. No resistant isolates were encountered in sensitivity testing. The low efficacy of this rifampin regimen in young children precludes its routine use as a chemoprophylactic agent for family contacts. The occurrence of three cases of invasive HIB infection in individuals outside the defined contact group raises concern regarding the efficacy of any chemoprophylactic regimen.

Clinical Trials as Topic↗

Nosocomial infections in a neonatal intensive care unit.

Based on five years of surveillance in a neonatal intensive care unit (NICU), host and therapeutic risk factors for nosocomial infection were determined and the impact of staffing and environment on the rate of nosocomial infection was evaluated. From January 1974 to February 1977, infants occupied a crowded, hectic NICU that lacked basic infection control features, and 5.2% of the infants had at least one major nosocomial infection. The risk of nosocomial infection was associated with low birth weight, patent ductus arteriosus, surgery, and multiple supportive measures. After a new NICU opened in February 1977, 0.9% of the patients had major nosocomial infections (relative risk [old nursery/new nursery] = 5.06; P less than 10(-5); 95% confidence interval, 2.62-9.73). Improvements included 50% more nurses, increased space per infant, convenient sinks, and isolation facilities. Host and therapeutic risk factors for nosocomial infections were comparable in the old and new nurseries. The decrease in the rate of nosocomial infections therefore appeared to be due to improved staffing and environment.

Birth Weight↗

In vitro antibacterial activity of fluorinated analogs of chloramphenicol and thiamphenicol.

We evaluated the in vitro antimicrobial activity of Sch 24893, Sch 25298, and Sch 25393, three novel analogs of chloramphenicol and thiamphenicol. All of the analogs had minimal inhibitory concentrations of less than or equal to 10 micrograms/ml for 18 chloramphenicol-thiamphenicol-resistant strains of Shigella dysenteriae and 21 strains of resistant Salmonella typhi. The analogs were also more active than were chloramphenicol and thiamphenicol against chloramphenicol-resistant enteric bacteria, including six strains of Escherichia coli, seven strains of Klebsiella pneumoniae, and two strains of Enterobacter cloacae. Fifty-three strains of ampicillin-resistant Haemophilus influenzae were uniformly susceptible to chloramphenicol, thiamphenicol, and the three analogs. Sch 25298 was the most active compound tested (minimal inhibitory concentration, 0.5 microgram/ml for all strains). Four of seven chloramphenicol-thiamphenicol-resistant Haemophilus strains were susceptible to the fluorinated analogs. Of the three Haemophilus strains which were resistant to chloramphenicol, thiamphenicol, and the analogs, two contained less than 10% of the chloramphenicol acetyltransferase activity of the strains which were resistant to only chloramphenicol and thiamphenicol. We conclude that fluorinated analogs of chloramphenicol and thiamphenicol have considerable in vitro activity against a broad spectrum of chloramphenicol-thiamphenicol-resistant, gram-negative bacteria.

Acetyltransferases↗

Horizontal nonparenteral spread of hepatitis B among children.

Two families with an unusually high incidence of hepatitis B infection (15 of 21 persons) were investigated over an 18-month period. Serologic evidence of past or present infection--hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), or antibody to hepatitis B core antigen (anti-HBc)--was found in 11 of the 12 members of one family, four of whom were chronic HBsAg carriers, and in four of nine members of a contact family. Anti-HBc was the only serologic marker of infection in five persons. Histocompatibility leukocyte antigen (HLA) typing failed to show an association between carriage of HBsAg and specific HLA markers. Chewing gum was a potential vehicle as HBsAg was detected in gum samples from three of four children who were chronic HBsAg carriers. Horizontal, nonparenteral transmission of hepatitis B virus probably accounted for the clustering of infection in these families, especially via the exchange among children of objects contaminated with oral secretions.

Adolescent↗

Haemophilus influenzae type B meningitis: a contagious disease of children.

The families of 126 consecutive patients with Haemophilus influenzae type B meningitis were surveyed for secondary invasive H influenzae disease among household contacts. A total of 120 of the families were contacted. In six cases no contact was possible and the medical record was reviewed. Some 555 household contacts were found; 31% (171) were under 5 years of age. A secondary case was defined as a household contact with H influenzae type B isolated from blood or cerebrospinal fluid more than 24 hours, but less than 30 days, after admission to hospital of the index case. Four secondary cases were identified, all in children aged under 5 years. The secondary attack rate in children under 5 years or less in the month after exposure to an index case was thus 2.3%, 800 times the endemic attack rate for H influenzae meningitis. This is a conservative estimate since five additional contact cases were documented, but not included in the secondary attack rate. Young contacts of a child with H influenzae meningitis are thus at significant risk of life-threatening secondary disease.

Age Factors↗

Bacteriology of sputum in cystic fibrosis: evaluation of dithiothreitol as a mucolytic agent.

Liquefaction and homogenization have been recommended to ensure accurate, representative sputum cultures. We evaluated dithiothreitol (DTT) as mucolytic agent for culturing sputum samples obtained from 79 cystic fibrosis (CF) patients. Liquefaction with DTT was not superior to direct plating of specimens for routine qualitative cultures. Unliquefied sputum cultures failed to direct 3 of 47 Pseudomonas aeruginosa isolates; DTT-treated specimens missed 5 of 13 Candida albicans isolates. Neither treated nor untreated sputum cultures were completely successful in detecting Staphylococcus aureus or Enterobacteriaceae. Since Haemophilus influenzae was recovered from only two qualitative cultures, we could not evaluate the effect of DTT on the receovery of this organism. However, 27 of 29 strains of H. influenzae were inhibited by concentrations of DTT near the recommended final working concentration of 50 micrograms/ml, suggesting that liquefaction might impair isolation of this organism. Liquefaction with DTT permitted quantitative cultures of CF sputum. The predominant pathogen in our CF population was P. aeruginosa; 37 of 43 (86%) patients were colonized with this organism. Median densities of rough and mucoid strains were 3.2 x 10(7) and 4.3 x 10(7) colony-forming units per ml, respectively. Previous oral antistaphylococcal therapy may have accounted for the observed low density of S. aureus (mean density, 3.5 x 10(3) colony-forming units per ml). We conclude that DTT treatment does not improve recovery of organisms from qualitative cultures but does facilitate quantitative studies of S. aureus and P. aeruginosa in CF sputum.

Candida albicans↗