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Biomedical subjects

D N Gerding

Publications and source records attributed to D N Gerding.

At least 37 records · Page 2Linked to original sources

Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.

Antimicrobial resistance results in increased morbidity, mortality, and costs of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms. A comprehensively applied infection control program will interdict the dissemination of resistant strains.

Anti-Bacterial Agents↗

Protein-losing enteropathy is associated with Clostridium difficile diarrhea but not with asymptomatic colonization: a prospective, case-control study.

A prospective, case-control study was performed in which enteric protein loss and nutritional status were measured in patients with symptomatic and asymptomatic infections due to Clostridium difficile. Enteric protein loss, measured by elevated levels of fecal alpha1-antitrypsin, was detected in 14 of 20 cases and controls with diarrhea (9 of 10 cases with C. difficile-associated diarrhea and 5 of 10 age-matched control with diarrhea not associated with C. difficile) compared with none of 20 asymptomatic cases and controls (10 colonized cases and 10 noncolonized controls without diarrhea who were matched by age and clinical diagnosis) (P < .0001). Cases and controls with diarrhea had higher prognostic nutritional index values (P = 0.005) and lower levels of serum albumin, transferrin, and cholesterol than did the asymptomatic cases and controls. Decreased nutritional status, measured by increased prognostic nutritional index values, was associated with the presence of diarrhea but not with the presence of C. difficile. Protein-losing enteropathy was associated with C. difficile only in the presence of diarrhea, and we did not detect an increased risk of protein-losing enteropathy or malnutrition as a consequence of asymptomatic colonization with C difficile.

Aged↗

Does antibiotic restriction prevent resistance?

Antimicrobial resistance among some hospital organisms has increased to a stage where it can no longer be tolerated. The need for preventive and corrective measures is urgent. There is an association between the use of antimicrobial agents and resistance that is likely causal. Alterations in antimicrobial usage have been shown to affect antimicrobial resistance rates, particularly with use of aminoglycosides. Efforts to improve antimicrobial use through educational efforts alone have been largely ineffective, even when coupled with quality management or clinical guideline aspects. Thus, further work is urgently needed to determine the impact of antimicrobial-use controls. Additional large-scale, well controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular biological organism typing, and precise resistance mechanism analysis will be required to determine the best methods to prevent and control this problem and ensure our optimal antimicrobial-use "stewardship." Consideration of the long-term effects of antimicrobial selection, dosage, and duration of treatment on resistance development should be a part of every antimicrobial treatment decision.

Anti-Bacterial Agents↗

Clostridium difficile-associated diarrhea and colitis.

OBJECTIVES: To review and summarize the status of diagnosis, epidemiology, infection control, and treatment of Clostridium difficile-associated disease (CDAD). DIAGNOSIS: A case definition of CDAD should include the presence of symptoms (usually diarrhea) and at least one of the following positive tests: endoscopy revealing pseudomembranes, stool cytotoxicity test for toxin B, stool enzyme immunoassay for toxin A or B, or stool culture for C difficile (preferably with confirmation of organism toxicity if a direct stool toxin test is negative or not done). Testing of asymptomatic patients, including those who are asymptomatic after treatment, is not recommended other than for epidemiologic purposes. Lower gastrointestinal endoscopy is the only diagnostic test for pseudomembranous colitis, but it is expensive, invasive, and insensitive (51% to 55%) for the diagnosis of CDAD. Stool culture is the most sensitive laboratory test currently in clinical use, but it is not as specific as the cell cytotoxicity assay. EPIDEMIOLOGY: C difficile is the most frequently identified cause of nosocomial diarrhea. The majority of C difficile infections are acquired nosocomially, and most patients remain asymptomatic following acquisition. Antimicrobial exposure is the greatest risk factor for patients, especially clindamycin, cephalosporins, and penicillins, although virtually every antimicrobial has been implicated. Cases of CDAD unassociated with prior antimicrobial or antineoplastic use are very rare. Hands of personnel, as well as a variety of environmental sites within institutions, have been found to be contaminated with C difficile, which can persist as spores for many months. Contaminated commodes, bathing tubs, and electronic thermometers have been implicated as sources of C difficile. Symptomatic and asymptomatic infected patients are the major reservoirs and sources for environmental contamination. Both genotypic and phenotypic typing systems for C difficile are available and have enhanced epidemiologic investigation greatly. INFECTION CONTROL: Successful infection control measures designed to prevent horizontal transmission include the use of gloves in handling body substances and replacement of electronic thermometers with disposable devices. Isolation, cohorting, handwashing, environmental disinfection, and treatment of asymptomatic carriers are recommended practices for which convincing data of efficacy are not available. The most successful control measure directed at reduction in symptomatic disease has been antimicrobial restriction. TREATMENT: Treatment of symptomatic (but not asymptomatic) patients with metronidazole or vancomycin for 10 days is effective; metronidazole may be preferred to reduce risk of vancomycin resistance among other organisms in hospitals. Recurrence of symptoms occurs in 7% to 20% of patients and is due to both relapse and reinfection. Over 90% of first recurrences can be treated successfully in the same manner as initial cases. Combination treatment with vancomycin plus rifampin or the addition orally of the yeast Saccharomyces boulardii to vancomycin or metronidazole treatment has been shown to prevent subsequent diarrhea in patients with recurrent disease.

Bacterial Proteins↗

Laboratory detection of Clostridium difficile. A comparison of media and incubation systems.

Parallel testing for culture recovery of Clostridium difficile was performed using three selective media in each of four anaerobic incubation environmental systems. Testing was completed on 67 stool samples from 60 hospitalized patients in whom C difficile-associated diarrhea was suspected. Three different media were evaluated: CCFA (modified cycloserine-cefoxitin-fructose agar), CCFA-PRAS (CCFA, prereduced-anaerobically-sterilized) and CMBA (modified cycloserine-mannitol-blood agar). The incubation systems compared were an anaerobic chamber (Model 800 Anaerobic Environmental System, Anaerobe Systems, San Jose, CA), the anaerobic jar (BBL, Cockeysville, MD), the anaerobic Bio-Bag (BBL), and the anaerobic pouch (BBL). C difficile was found in 16 samples collected from 15 patients. Comparing recovery on the various types of media in all four anaerobic atmospheres, C difficile was recovered on all (64) CCFA plates, 56 of 64 CCFA-PRAS plates, and 43 of 64 CMBA plates (P < .03 comparing CCFA and CMBA). Of the 48 plates in each incubation system that were inoculated with specimens positive for C difficile, the organism was recovered from 43 plates in the anaerobe chamber, 41 incubated in an anaerobe jar, 40 in the Bio-Bag, and 39 incubated in the GasPak pouch, all providing similar recovery of C difficile (P = .08). The CCFA-PRAS and CMBA media demonstrated less inhibition of normal stool flora compared to the CCFA. Overall CCFA that was anaerobically reduced at least 4 hours before use, and contained the original concentration of antimicrobial agents described by George and colleagues, was superior to CMBA for recovery of C. difficile.

Clinical Laboratory Techniques↗

Foot infections in diabetic patients: the role of anaerobes.

The prevalence of anaerobic bacteria in cultures of specimens from foot infections in diabetic patients is dependent upon the method of obtaining the specimen, the care with which it is transported anaerobically, and the sophistication of the laboratory methods. The rate at which anaerobes are isolated with use of the best methods ranges from 74% to 95% of patients, but it is only 41% to 53% in clinical studies of patients with limb-threatening infection. The mean number of bacterial isolates from an infected foot ranges from 4.1 to 5.8, of which 1.2 to 2.6 isolates are anaerobic. Most anaerobic isolates are gram-positive, and Peptostreptococcus species are most common. Bacteroides species are the most common anaerobic gram-negative isolates. Treatment covering anaerobic bacteria is included in most empirical regimens, but the use of agents that are modestly active against anaerobic organisms (i.e., fluoroquinolones or trimethoprim-sulfamethoxazole) has also been successful. Surgical debridement and drainage are essential adjuncts to antimicrobial therapy and may assist in the control of anaerobic infection. Questions regarding management of such infections parallel those regarding management of polymicrobial intraabdominal infections, but to date, studies of the former have been much less sophisticated than those of the latter.

Bacteria, Anaerobic↗

Selective neutralization of a bacterial enterotoxin by serum immunoglobulin A in response to mucosal disease.

One-third of convalescent-phase serum samples (6 of 18) from patients with Clostridium difficle-associated diarrhea demonstrated neutralization of the clostridial enterotoxin, toxin A. Although appreciable amounts of toxin A-specific immunoglobulin G (IgG) and IgA were present in these sera, the ability to neutralize the cytotoxic activity of toxin A on OTF9-63 cells in vitro was confined to the IgA fraction and the IgA1 subclass in serum samples from all six patients. In contrast to the patients with C. difficile diarrhea, this activity was present in both the IgA and IgG fractions in sera from two C. difficile-infected patients without diarrhea, one of whom presented with a splenic abscess. Sera and purified IgA which neutralized the cytotoxicity of toxin A on OTF9-63 cell cultures in vitro also neutralized the enterotoxicity of toxin A in rabbit ileal loops in vivo. This activity was not Fc dependent, since IgA retained neutralizing activity after pepsin digestion and F(ab')2 purification. The transition from nonneutralizing toxin A-specific IgA in the acute-phase sera to neutralizing specific IgA in the convalescent-phase sera was accompanied by a shift from a polymeric to a predominantly monomeric form of specific IgA. However, the neutralizing activity in convalescent-phase sera was present as both monomeric and polymeric IgA. Convalescent-phase sera from other patients with C. difficile diarrhea that failed to neutralize toxin A also failed to produce a predominantly monomeric-form specific IgA response. We conclude that serum IgA, not IgG, characteristically neutralizes toxin A in patients with C. difficile diarrhea who develop neutralizing systemic responses. This neutralization of an enteric bacterial toxin is a unique and selective role for serum IgA which provides a novel functional link between the systemic and mucosal immune systems.

Acute Disease↗

Comparison of arbitrarily primed PCR with restriction endonuclease and immunoblot analyses for typing Clostridium difficile isolates.

Arbitrarily primed PCR (AP-PCR) was used to genotype 26 clinical isolates of Clostridium difficile previously analyzed by immunoblotting (IB) and 20 isolates typed by restriction endonuclease analysis (REA) with HindIII. Two levels of differentiation were achieved with the AP-PCR approach by use of two different arbitrary primers. With the 19-mer arbitrary primer T-7 (first level of differentiation), a good correlation was found between IB and AP-PCR typing. Twenty isolates grouped into six IB types were separated into seven major AP-PCR types. These seven AP-PCR groups were further discriminated into 12 subtypes after genotyping with the arbitrary primer PG-05 (second level of differentiation). The remaining six isolates, all of different IB types, showed a unique and distinct DNA banding pattern with both of the arbitrary primers, T-7 and PG-05. Twenty isolates representing 20 REA types from 15 REA groups were resolved into 13 AP-PCR DNA profiles with the arbitrary primer T-7. A good correlation was found at this level of differentiation between the major REA groups, Y and M, and AP-PCR typing. While AP-PCR with this primer failed to differentiate isolates in REA groups J, G, R, and B, AP-PCR with PG-05 resolved these four isolates into four distinct AP-PCR types. In addition, one of three M strains and one of four Y strains displayed a slightly different DNA banding pattern by AP-PCR (with PG-05) from that of the other strains in the group. We conclude that AP-PCR is a rapid and sensitive method which not only complements other typing schemes but also may be a substitute and prove to be especially suited for immediate epidemiological tracking of nosocomial infections due to C. difficile.

Bacterial Typing Techniques↗

Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use.

OBJECTIVE: To report the investigation and effective control of a nosocomial epidemic of Clostridium difficile-associated diarrhea. DESIGN: Concurrent surveillance for identification of new nosocomial cases, retrospective case-control analysis, and hospital formulary control of antibiotic use. SETTING: University-affiliated Veterans Affairs Medical Center located in southwestern United States. PATIENTS: Hospitalized patients who developed diarrhea submitted stool specimens for cytotoxin assay. Patients who were positive for cytotoxin were compared with control patients without infection. MEASUREMENTS: Isolates of C. difficile were typed by restriction endonuclease analysis. Antimicrobial agent use from hospital pharmacy records and selected patient data from chart review were correlated with frequency of specific laboratory abnormalities. RESULTS: For 13 months, the monthly incidence of C. difficile infection averaged more than five times that for the previous 21 months. Stool specimens from 34 patients (59%) contained a single strain (restriction enzyme analysis type J7). Clindamycin was statistically associated with the epidemic as shown by the following: clindamycin use at our center compared with national normal values, clindamycin use for years before compared with during the epidemic, monthly use of clindamycin compared with monthly frequency of infection, frequency of infection in patients receiving clindamycin compared with that in patients receiving other antimicrobial agents, and amount of clindamycin used by infected patients compared with that used by control patients. Restricting clindamycin use led to a prompt disease in infection rate and the type J7 organisms. CONCLUSION: A nosocomial epidemic of C. difficile diarrhea was controlled by analysis of antibiotic use patterns and by subsequent restriction of clindamycin.

Arizona↗

Effectiveness of liquid soap vs. chlorhexidine gluconate for the removal of Clostridium difficile from bare hands and gloved hands.

OBJECTIVE: To compare liquid soap versus 4% chlorhexidine gluconate in 4% alcohol for the decontamination of bare or gloved hands inoculated with an epidemic strain of Clostridium difficile. DESIGN: C difficile (6.7 log10 colony-forming units [CFU], 47% spores), was seeded onto bare or latex gloved hands of ten volunteers and allowed to dry. Half the volunteers initially washed with soap and half with chlorhexidine, followed by the other agent 1 week later. Cultures were done with Rodac plates at three sites on the hand: finger/thumbtips, the palmar surfaces of the fingers, and the palm. Statistical comparison was by paired Student's t test. RESULTS: On bare hands, soap and chlorhexidine did not differ in residual bacterial counts on the finger/thumbtips (log10 CFU, 2.0 and 2.1, P = NS) and fingers (log10 CFU, 2.4 and 2.5, P = NS). Counts were too high on bare palms to quantitate. On gloved hands, soap was more effective than chlorhexidine on fingers (log10 CFU 1.3 and 1.7, P < .01) and palms (log10 CFU 1.5 and 2.0, P < .01), but not finger/thumbtips (log10 CFU 1.6 with each, P = NS). Residual C difficile counts were lower on gloved hands than bare hands (P < 0.01 to < 0.0001). CONCLUSIONS: The two agents did not differ significantly in residual counts of C difficile on bare hands, but on gloved hands residual counts were lower following soap wash than following chlorhexidine wash. These observations support the use of either soap or chlorhexidine as a handwash for removal of C difficile, but efficacy in the prevention of C difficile transmission must be determined by prospective clinical trials.

Aerosols↗

Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991.

OBJECTIVES: To understand the epidemiology, risks, and management of Clostridium difficile-associated disease (CDAD) and to establish and evaluate reliable methods of surveillance. DESIGN: Case finding was done by daily ward and laboratory rounds. The criteria for CDAD diagnosis were: at least four unformed stools per day for 2 days and a positive culture or cytotoxin for C difficile, or positive endoscopy or autopsy for pseudomembranes. SETTING: The surveillance covered all patients from 1982 through 1991 in the 820-bed Minneapolis Veterans Affairs Medical Center. PARTICIPANTS: The criteria were met by 908 patients. Medical service patients numbered 488; surgical patients, 420. Frequencies ranged from a high of 149 cases in 1982 to a low of 50 cases in 1989. RESULTS: Stool specimens were obtained on 898 (99%) of the 908 CDAD patients. Stools were culture-positive in 864 (96%) of 898, cytotoxin-positive in 569 (63%) of 898. Endoscopy was performed on 196 (22%) of the 908 patients, and 80 (41%) of 196 patients had pseudomembranes. Ten (1%) of the 908 patients were diagnosed by endoscopy without a stool specimen, or at autopsy. No treatment was needed for 135 (15%) of the 908 CDAD patients, and 19 (2%) of the 908 died before treatment was started. Oral metronidazole was the treatment for 632 (70%) of 908 patients (1% intolerance, 2% failure, 7% relapse) and oral vancomycin was given to 122 (13%) of 908 patients (1% intolerance, 1% failure, 10% relapse). Twelve patients had pseudomembranous colitis at autopsy, and it was the primary cause of death in 5 (0.6%) of 908. CONCLUSIONS: CDAD usually responds to oral metronidazole or vancomycin but is nonetheless responsible for a high morbidity and occasional mortality in patients even when the diagnosis and treatment are pursued aggressively.

Administration, Oral↗

Wide diversity of Clostridium difficile types at a tertiary referral hospital.

Nosocomial Clostridium difficile infection was investigated at a hospital with 15 cases of C. difficile diarrhea per 1000 discharges. From January 1991 to May 1991, patients admitted or transferred to five wards or units had weekly rectal swabs taken for culture; in addition, all cytotoxin-positive stools were cultured. Restriction enzyme analysis (REA) was used for molecular typing. Among 205 isolates from 39 patients with C. difficile diarrhea and 67 asymptomatically colonized, 55 distinct REA banding patterns were identified. Evidence for patient-to-patient transmission was limited, in that numerous strains were found even among clustered cases of diarrhea. Patients who acquired C. difficile in the community or other hospitals constituted 32% of culture-positive patients and contributed 44% of the REA types. Diversity of C. difficile strains was in part the result of patients acquiring C. difficile in the community or other hospitals. High incidences of nosocomial C. difficile diarrhea do not necessarily indicate clonal epidemics.

Aged↗

Comparison of restriction endonuclease analysis, ribotyping, and pulsed-field gel electrophoresis for molecular differentiation of Clostridium difficile strains.

A combined clinical and molecular epidemiologic analysis of 46 strains of Clostridium difficile, including 16 nosocomial isolates from one ward (outbreak ward) plus 17 other nosocomial isolates and 13 community-acquired isolates, was performed. HindIII digests of total cellular DNA were analyzed by restriction enzyme analysis (REA) and ribotyping; SmaI digests were analyzed by pulsed-field gel electrophoresis (PFGE). Isolates were assigned to typing groups on the basis of the profiles detected; isolates with closely related profiles were assigned to subgroups. The 16 isolates from the outbreak ward were resolved by both REA and PFGE into five distinct groups; 13 isolates represented two REA groups and three PFGE groups and two isolates were resolved as distinct groups by both techniques. DNA obtained from one isolate was persistently partially degraded, precluding analysis by PFGE. Seventeen sporadic nosocomial isolates were resolved by REA and PFGE into comparable numbers of groups (i.e., nine groups) and subgroups (i.e., 15 and 14 subgroups, respectively), with two isolates not evaluable by PFGE. The 13 epidemiologically unrelated community-acquired isolates were assigned to 11 groups by REA and to 12 groups by PFGE. Overall, ribotyping identified only nine groups among the 46 isolates. We conclude that REA and PFGE have comparable discriminatory powers for epidemiologic typing of C. difficile isolates and that ribotyping is appreciably less discriminatory. For a few isolates, partial DNA degradation prevented analysis by PFGE but not by REA or ribotyping; the cause of the degradation is unknown.

Bacterial Proteins↗

Optimal methods for identifying Clostridium difficile infections.

The major controversy in the diagnosis of symptomatic gastrointestinal infection due to Clostridium difficile is whether laboratory evidence of the C. difficile organism in culture is sufficient or if evidence of one of the C. difficile toxins in stool should be required. Cultures performed properly on selective media currently are the most sensitive method for detection of C. difficile, whereas the cell cytotoxin assay for detection of toxin B is the most specific. Stool specimens from patients with clinical diarrhea are sometimes found to be culture-positive for C. difficile but assay-negative for cytotoxin. Samples from these patients can be viewed as false-positive by culture or false-negative by cytotoxin test. Evidence from endoscopy indicates that some patients whose stool is culture-positive for the organism but assay-negative for toxin do have pseudomembranous colitis, but its incidence among such patients (11%) is lower than that among patients whose stool is culture- and assay-positive (51%). Response to treatment with vancomycin or metronidazole is similar in the two groups of patients, and withholding treatment from patients whose stool contains C. difficile but not cytotoxin may result in increased morbidity and mortality. Up to one-third of C. difficile organisms from stool specimens that are culture-positive but assay-negative are incapable of producing cytotoxin in vitro, a finding that suggests these organisms may not be the cause of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗