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Biomedical subjects

D N Gerding

Publications and source records attributed to D N Gerding.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of vancomycin and metronidazole for eradication of asymptomatic Clostridium difficile fecal excretion as a means of controlling nosocomial outbreaks of C. difficile diarrhea. DESIGN: Randomized, placebo-controlled, non-blinded trial. SETTING: Six hundred-bed regional referral Veterans Affairs Medical Center. PATIENTS: Thirty patients excreting C. difficile without diarrhea or abdominal symptoms. INTERVENTIONS: All patients were randomized to receive 10 days of oral vancomycin, 125 mg four times daily; metronidazole, 500 mg twice daily; or placebo, three times daily. MEASUREMENTS: Stool cultures were obtained during treatment and for 2 months after treatment. All C. difficile isolates were typed by restriction endonuclease analysis (REA). RESULTS: Clostridium difficile organisms were not detected during and immediately after treatment in 9 of 10 patients treated with vancomycin compared with 3 of 10 patients treated with metronidazole (P = 0.02) and 2 of 10 patients in the placebo group (P = 0.005). The fecal vancomycin concentration was 1406 +/- 1164 micrograms/g feces, but metronidazole was not detectable in 9 of 10 patients. Eight of the nine evaluable patients who had negative stool cultures after treatment with vancomycin began to excrete C. difficile again 20 +/- 8 days after completing treatment. Three of these patients received additional antibiotics before C. difficile excretion recurred, and five acquired new C. difficile REA strains. Four of six patients who received only vancomycin before C. difficile excretion recurred were culture-positive at the end of the study compared with one of nine patients who received only placebo (P = 0.047). CONCLUSIONS: Asymptomatic fecal excretion of C. difficile is transient in most patients, and treatment with metronidazole is not effective. Although treatment with vancomycin is temporarily effective, it is associated with a significantly higher rate of C. difficile carriage 2 months after treatment and is not recommended.

Aged↗
PubMed1992

Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection.

The frequency of introduction and spread of specific Clostridium difficile strains among hospitalized patients were assessed by serial cultures of patients admitted to a medical-surgical ward with endemic C. difficile-associated diarrhea. Stool cultures were obtained from 634 (94%) of 678 consecutive admissions to the ward (ward admissions), and all C. difficile isolates were typed by restriction endonuclease analysis. Sixty-five ward admissions introduced C. difficile to the ward, and 54 initially culture-negative admissions acquired C. difficile on the ward. Ward admissions hospitalized within the prior 30 days in the medical center were more likely to be culture-positive for C. difficile at admission to the study ward than those not previously hospitalized at the institution (16% vs. 7%, P less than .001). Nosocomial acquisition of a C. difficile strain was preceded by a documented introduction of that strain to the ward by another asymptomatic ward admission in 16 (84%) of 19 instances, suggesting that C. difficile-colonized new admissions are a major source of nosocomial C. difficile infections.

Bacterial Typing Techniques↗
PubMed1992

Systemic and mucosal antibody responses to toxin A in patients infected with Clostridium difficile.

The systemic and mucosal humoral response to toxin A, the primary virulence factor of Clostridium difficile, was measured in sera and intestinal secretions from 21 patients with C. difficile diarrhea, 9 asymptomatic C. difficile fecal excretors, and 10 noncolonized control subjects. Toxin A-specific IgG was higher in convalescent sera of the patients with diarrhea (mean +/- SE, 990 +/- 260 ng/mL) than in acute sera (620 +/- 150 ng/mL), in sera from asymptomatic excretors (410 +/- 140 ng/mL), or control subjects (320 +/- 50 ng/mL; P < .05 convalescent vs. control). The pattern of toxin A-specific serum IgA and intestinal secretory IgA levels was similar to that of serum IgG in these groups. Neutralization of toxin A was demonstrated in 5 of 14 convalescent sera but only 1 of 13 acute sera (P = .04). However, the presence of neutralizing activity was independent of the subsequent clinical response. Therefore, most patients convalescent from C. difficile diarrhea demonstrate systemic and mucosal antibodies to toxin A, but these antibodies following natural infection do not appear to alter the clinical course of C. difficile infection.

Adult↗
PubMed1992

Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy.

Combination antimicrobial agent therapy has been advocated for treatment of gram-negative bacteremia, including that caused by Klebsiella spp. We performed a prospective, observational, 10-hospital collaborative study to evaluate the efficacy of antibiotic combination therapy versus that of monotherapy for 230 consecutive patients with Klebsiella bacteremia. The species involved were K. pneumoniae (82%), K. oxytoca (15%), and K. ozaenae (0.4%). Of the bacteremias, 26% were polymicrobial in nature. A total of 53% of cases were nosocomial infections. The most common portals were the urinary tract (28%), biliary tract (12%), lung (10%), and abdomen (9%). Some 49 and 51% of the patients had received monotherapy and antibiotic combination therapy (beta-lactam plus aminoglycoside), respectively; 14-day mortalities in the two groups were 20 and 18%, respectively. However, for the subgroup of patients who experienced hypotension within 72 h prior to or on the day of the positive blood culture, those patients who received combination therapy experienced significantly lower mortality (24%) than did those who received monotherapy (50%). We conclude that monotherapy with an antibiotic that is active in vitro against Klebsiella (beta-lactam or aminoglycoside) is sufficient therapy for less severely ill patients (immunocompetent, urinary tract portal, mentally alert, normal vital signs). On the other hand, for severely ill patients who experience hypotension, antibiotic combination therapy with a beta-lactam and an aminoglycoside agent is preferred.

Adolescent↗
PubMed1992

Comparison of the VIDAS Clostridium difficile toxin A immunoassay with C. difficile culture and cytotoxin and latex tests.

The VIDAS Clostridium difficile toxin A immunoassay (CDA) is a new, automated, enzyme-linked fluorescent-antibody assay for detection of C. difficile toxin A antigen in stool specimens. Simultaneous, parallel testing was performed by using the VIDAS CDA, the Culturette brand CDT latex test for C. difficile antigens, and conventional laboratory cell culture tests for C. difficile, cytotoxicity and C. difficile culture. One hundred ninety-four consecutive fresh soft or liquid stool samples submitted for C. difficile testing between July and September 1990 were evaluated. Of the 194 samples tested, 19 (10%) were from 16 patients who met our case definition for C. difficile-associated disease. The in vitro tests were evaluated in relation to two forms of a clinical case definition. In one form, a positive culture for toxin-producing C. difficile or a positive cytotoxin result obtained directly from the stool specimen was required as laboratory evidence of C. difficile. In the other, a positive result of any of the four laboratory tests was accepted for the laboratory portion of the case definition. No significant difference between the sensitivity of the VIDAS CDA and that of the Culturette brand CDT latex test was found (48 to 58% sensitivity for the CDT latex test and 52 to 63% sensitivity for the VIDAS CDA compared with 93 to 100% sensitivity for culture and 70 to 100% sensitivity for cytotoxin testing). The performance of the VIDAS CDA, however, was hampered by a high percentage of tests (19%) which gave an uninterpretable result.

Bacterial Toxins↗
PubMed1991

gyrA mutations in ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus from Indiana, Minnesota, and Tennessee.

Mutational changes occurring at amino acid codons 84 and 85 located in the gyrA gene of methicillin-resistant Staphylococcus aureus (MRSA) were studied using radiolabeled oligonucleotide probes to examine the incidence of these ciprofloxacin resistance determinants in 30 MRSA isolates from Indiana, Minnesota, and Tennessee. Four separate oligonucleotide probes, one each corresponding to the wild-type sequence, a mutation at codon 84 (nucleotide 251), a mutation at codon 85 (nucleotide 253), and mutations at both, were used to examine the total genomic DNA from each of the 30 isolates, which had been restricted, electrophoresed, and Southern blotted. The probes indicated that 15 of the 28 ciprofloxacin-resistant isolates gave results consistent with a single mutation at codon 84. Four of the 28 ciprofloxacin-resistant strains had results consistent with a mutation at codon 84 and possibly at codon 85. The two ciprofloxacin-sensitive isolates from Tennessee showed homology with the wild-type probe sequence. Five isolates (4, Minnesota; 1, Tennessee) had no homology with any probe. By oligonucleotide probes, ciprofloxacin-resistant MRSA from diverse geographic regions contained similar gyrA mutations at codons 84 or 85 in 19 of 28 ciprofloxacin-resistant isolates.

Base Sequence↗
PubMed1991

Aminoglycoside resistance and aminoglycoside usage: ten years of experience in one hospital.

For 10 years the 700-bed Minneapolis Veterans Affairs Medical Center has conducted a policy of carefully controlled aminoglycoside usage and monitoring of resistance of over 25,000 aerobic and facultative gram-negative bacillary isolates to the aminoglycosides. On two occasions during the 1980s, our experience of introducing amikacin at a high level of usage was associated with a significant reduction in resistance to gentamicin and tobramycin among gram-negative bacilli. Rapid reintroduction of gentamicin usage in 1982 after the first amikacin period was associated with a significant and rapid increase in gentamicin and tobramycin resistance. However, in 1986, gentamicin was again reintroduced to this institution at an initially modest level, and the percentage of usage of gentamicin was gradually increased over a 15-month period without a significant change in resistance to gentamicin, tobramycin, or amikacin while maintaining an overall 68% gentamicin usage and 30% amikacin usage. Aminoglycoside usage (measured as patient days) rose steadily from under 2,000 patient days per quarter in 1980 and 1981 to over 3,000 days per quarter in 1985. Since 1985, usage has declined to under 2,500 patient days per quarter in 1990. This usage rise and fall occurred during a steadily declining daily patient census that was 590 in 1980 and 465 in 1989. A move to a new hospital building in June 1988 was associated with an additional significant decline in resistance to all aminoglycosides (P less than 0.05), continuing a trend that was evident for the year preceding the move. Resistance to aminoglycoside antibiotics is now at the lowest level in 10 years at this institution, with only one gram-negative organism, Pseudomonas aeruginosa, that exhibits more than 5% resistance to gentamicin and no gram-negative species that are more than 5% resistant to amikacin and tobramycin.

Amikacin↗
PubMed1991

Evaluation of cycloserine-cefoxitin-fructose agar and cycloserine-cefoxitin-fructose broth for recovery of Clostridium difficile from environmental sites.

Cycloserine-cefoxitin-fructose agar (CCFA) and cycloserine-cefoxitin-fructose broth (CCFB) containing either 500 or 250 micrograms of cycloserine per ml were compared for efficacy in the isolation of Clostridium difficile from hospital ward environmental sites. A RODAC imprint technique was used to inoculate prereduced CCFA. Moistened swabs were used to inoculate prereduced CCFB from environmental sites immediately adjacent to the RODAC sample sites. CCFA (6% positive) was significantly more sensitive than CCFB (3% positive; P less than 0.005), regardless of the cycloserine concentration. When the CCFA cycloserine concentration was decreased from 500 to 250 micrograms/ml, the overall rate of positive cultures rose from 4 to 17%. Medium containing 500 micrograms of cycloserine per ml may be too inhibitory to isolate many moderately sensitive strains of C. difficile from environmental sites. Regardless of the cycloserine concentration, the CCFA RODAC imprint technique is superior to the CCFB method.

Agar↗
PubMed1991

DNA fingerprinting by pulsed field gel electrophoresis and ribotyping to distinguish Pseudomonas cepacia isolates from a nosocomial outbreak.

We typed 40 isolates of Pseudomonas cepacia obtained from patients involved in a single outbreak using pulsed field gel electrophoresis and ribotyping. All isolates from the majority of the patients, 16 of 18 (89%), were included in a single group. These typing methods should aid in the clarification of the epidemiology of infection with P. cepacia.

Bacterial Typing Techniques↗
PubMed1991

Aminoglycosides versus beta-lactams in gram-negative pneumonia.

Newer beta-lactam antibiotics with high levels of activity against gram-negative aerobic bacilli (including Pseudomonas aeruginosa) such as cefoperazone, ceftazidime, imipenem, and aztreonam may be suitable for monotherapy of gram-negative pneumonia. Aminoglycoside antibiotics (gentamicin, tobramycin, amikacin are also highly active against these same organisms and have been more extensively used, but are both ototoxic and nephrotoxic. Key therapeutic questions are whether beta-lactams can safely replace aminoglycosides for the treatment of gram-negative pneumonia, and whether monotherapy or aminoglycoside and beta-lactam combination antibiotic treatment is superior. There is remarkably little definitive clinical data in the literature to answer these questions, but available studies suggest that beta-lactam monotherapy may be adequate for Escherichia coli and Klebsiella pneumoniae pneumonias, but that combination therapy may be preferred for Pseudomonas aeruginosa, Serratia sp, Enterobacter sp, and Acinetobacter sp, largely based on rates of bacterial persistence and emergence of resistance. At this time, there are more data available to support aminoglycoside monotherapy than beta-lactam monotherapy in gram-negative pneumonia and remarkably little data to suggest superiority of two antibiotics over single agents when they have been compared prospectively. Thus, combination therapy remains a conservative recommendation until better studies are available.

Aminoglycosides↗
PubMed1991

Sputum antimicrobial levels and clinical outcome in bronchitis.

The role of antimicrobials in the treatment of bronchitis remains controversial. Antimicrobials are rarely indicated in acute bronchitis. Antimicrobials are indicated in a subset of patients with acute exacerbations of chronic bronchitis. The efficacy of an antimicrobial agent in bronchitis can be estimated by the ratio of the sputum concentration of the antimicrobial to its in vitro activity against common respiratory pathogens (S/M90). These S/M90 rates are presented in tabular form. However, given the lack of solid data to support antimicrobial treatment for most episodes of bronchitis, use of the S/M90 to select antimicrobial therapy remains theoretical rather than of proven clinical benefit.

Acute Disease↗
PubMed1990

Nosocomial Clostridium difficile colonisation and disease.

To assess the risk of acquiring Clostridium difficile diarrhoea or colitis in patients colonised with C difficile, rectal swabs taken weekly for 9 weeks from patients with long-term (at least 7 days) hospital stays on three wards were cultured for C difficile. 60 (21%) of 282 patients were culture-positive for C difficile during their hospital stay, of whom 51 were symptom-free faecal excretors. C difficile diarrhoea developed in the other 9 patients; 2 were culture-positive for C difficile and had diarrhoea at the time of first culture, and 7 had diarrhoea or pseudomembranous colitis after 1-6 previously negative weekly rectal cultures. All patients with diarrhoea were on one ward, but symptom-free, excretors were found on all wards. HindIII chromosomal restriction endonuclease analysis (REA) of the C difficile isolates revealed 18 distinct types. All isolates from the patients with diarrhoea were one of two nearly identical REA types, B or B2. 26 of the 29 total B/B2 isolates were from patients on the same ward, which points to a nosocomial outbreak. The symptom-free excretors were not at increased risk of subsequent clinical illness.

Aged↗
PubMed1990

Prospective, controlled study of vinyl glove use to interrupt Clostridium difficile nosocomial transmission.

PURPOSE: Despite recognition that Clostridium difficile diarrhea/colitis is a nosocomial infection, the manner in which this organism is transmitted is still not clear. Hands of health care workers have been shown to be contaminated with C. difficile and suggested as a vehicle of transmission. Therefore, we conducted a controlled trial of the use of disposable vinyl gloves by hospital personnel for all body substance contact (prior to the institution of universal body substance precautions) to study its effect on the incidence of C. difficile disease. PATIENTS AND METHODS: The incidence of nosocomial C. difficile diarrhea was monitored by active surveillance for six months before and after an intensive education program regarding glove use on two hospital wards. The interventions included initial and periodic in-services, posters, and placement of boxes of gloves at every patient's bedside. Two comparable wards where no special intervention was instituted served as controls. RESULTS: A decrease in the incidence of C. difficile diarrhea from 7.7 cases/1,000 patient discharges during the six months before intervention to 1.5/1,000 during the six months of intervention on the glove wards was observed (p = 0.015). No significant change in incidence was observed on the two control wards during the same period (5.7/1,000 versus 4.2/1,000). Point prevalence of asymptomatic C. difficile carriage was also reduced significantly on the glove wards but not on the control wards after the intervention period (glove wards, 10 of 37 to four of 43, p = 0.029; control wards, five of 30 to five of 49, p = 0.19). The cost of 61,500 gloves (4,505 gloves/100 patients) used was $2,768 on the glove wards, compared with $1,895 (42,100 gloves; 3,532 gloves/100 patients) on the control wards. CONCLUSIONS: Vinyl glove use was associated with a reduced incidence of C. difficile diarrhea and is indirect evidence for hand carriage as a means of nosocomial C. difficile spread.

Clostridioides difficile↗
PubMed1990

Clostridium difficile diarrhea and colonization after treatment with abdominal infection regimens containing clindamycin or metronidazole.

One hundred fifty-six patients with presumed or documented abdominal infections were treated with amikacin/metronidazole/placebo (Group 1, 56 patients), amikacin/clindamycin/placebo (Group 2, 57 patients), or amikacin/clindamycin/ampicillin (Group 3, 43 patients) to determine both the therapeutic efficacy of the various regimens and the type of complications due to Clostridium difficile. C. difficile diarrhea occurred in 15 of 156 patients (9.6%), and C. difficile colonization occurred in 14 of 156 patients (9%) during treatment and 30 days of follow-up. The number of C. difficile diarrhea cases in Group 1 (3 of 56) was significantly lower than in Group 2 (9 of 57, p less than 0.05), but not in Group 3 (3 of 43). Exclusion of all patients who received other antibiotics in the 30-day poststudy period revealed no C. difficile diarrhea or colonization in Group 1 (0 of 13) and an acquisition rate of 31% (14 of 45) with the regimens containing clindamycin (p less than 0.02). Successful treatment outcomes (106 evaluable patients) were not statistically different among the three groups (Group 1, 64%; Group 2, 76%; and Group 3, 88%), but these data were difficult to interpret because, by chance, significantly more patients in Group 1 had bacteremia at entry (p less than 0.01), and patients in Group 3 had significantly more biliary tract infections (p less than 0.02) and significantly more favorable acute physiology scores (p less than 0.05). Use of metronidazole can reduce complications related to C. difficile, particularly if additional antimicrobials other than aminoglycosides are avoided.

Abdomen↗