Strategies to Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Microorganisms in Hospitals. A challenge to hospital leadership.

OBJECTIVE: To provide hospital leaders with strategic goals or actions likely to have a significant impact on antimicrobial resistance, outline outcome and process measures for evaluating progress toward each goal, describe potential barriers to success, and suggest countermeasures and novel improvement strategies. PARTICIPANTS: A multidisciplinary group of experts was drawn from the following areas: hospital epidemiology and infection control, infectious diseases (including graduate training programs), clinical practice (including nursing, surgery, internal medicine, and pediatrics), pharmacy, administration, quality improvement, appropriateness evaluation, behavior modification, practice guideline development, medical informatics, and outcomes research. Representatives from appropriate federal agencies, the Joint Commission on Accreditation of Healthcare Organizations, and the pharmaceutical industry also participated. EVIDENCE: Published literature, guidelines, expert opinion, and practical experience regarding efforts to improve antibiotic utilization and prevent and control the emergence and dissemination of antimicrobial-resistant microorganisms in hospitals. CONSENSUS PROCESS: Participants were divided into two quality improvement teams: one focusing on improving antimicrobial usage and the other on preventing and controlling transmission of resistant microorganisms. The teams modeled the process a hospital might use to develop and implement a strategic plan to combat antimicrobial resistance. CONCLUSIONS: Ten strategic goals and related process and outcome measures were agreed on. The five strategic goals to optimize antimicrobial use were as follows: optimizing antimicrobial prophylaxis for operative procedures; optimizing choice and duration of empiric therapy; improving antimicrobial prescribing by educational and administrative means; monitoring and providing feedback regarding antibiotic resistance; and defining and implementing health care delivery system guidelines for important types of antimicrobial use. The five strategic goals to detect, report, and prevent transmission of antimicrobial resistant organisms were as follows: to develop a system to recognize and report trends in antimicrobial resistance within the institution; develop a system to rapidly detect and report resistant microorganisms in individual patients and ensure a rapid response by caregivers; increase adherence to basic infection control policies and procedures; incorporate the detection, prevention, and control of antimicrobial resistance into institutional strategic goals and provide the required resources; and develop a plan for identifying, transferring, discharging, and readmitting patients colonized with specific antimicrobial-resistant pathogens.

Possible nosocomial transmission of Pseudomonas cepacia in patients with cystic fibrosis.

OBJECTIVE: To determine whether nosocomial transmission of Pseudomonas cepacia occurred at a hospital with endemic P cepacia infection of patients with cystic fibrosis. DESIGN: Two retrospective case-control studies. SETTING: A large pediatric cystic fibrosis center. PARTICIPANTS: To assess risk factors for acquisition of P cepacia, 18 cases, defined as any patient with cystic fibrosis with first documented isolation of P cepacia in 1988 or 1989, were compared with 18 matched P cepacia-negative controls with cystic fibrosis. To assess potential modes of nosocomial P cepacia transmission, 14 cases with a hospitalization(s) between their last P cepacia-negative culture and first P cepacia-positive culture were compared with 14 hospitalized P cepacia-negative controls with cystic fibrosis. METHODS: Handwiping cultures (N = 68) and selective environmental cultures were performed. MAIN RESULTS: Cases tended to be more likely than controls to have been hospitalized at the cystic fibrosis center in the 3 months before their first P cepacia-positive culture (P = .08). In addition, cases tended to be more likely than hospitalized controls with cystic fibrosis to have had a P cepacia-positive roommate (P = .06) before becoming colonized with P cepacia organisms. Pseudomonas cepacia was cultured from the hands of two individuals: a P cepacia-colonized patient who had just undergone chest physiotherapy and consequent coughing and the investigator who shook the P cepacia-positive patient's hand after the patient's procedure. CONCLUSIONS: These results suggest that in this cystic fibrosis center, hospitalization is a risk factor for P cepacia acquisition and that person-to-person transmission of P cepacia may occur in the hospital via hand contact.

Acquisition of Pseudomonas cepacia at summer camps for patients with cystic fibrosis. Summer Camp Study Group.

To assess the risk of acquisition of Pseudomonas cepacia by person-to-person transmission at cystic fibrosis summer camps, we conducted in 1990 a study at three camps attended by patients with cystic fibrosis who had P. cepacia infection and patients without P. cepacia infection but who were considered susceptible to infection. We obtained sputum or throat cultures from campers on their arrival at, weekly during, at the end of, and 14 to 30 days after camp. We compared the incidence of sputum conversion of patients at camp with that of patients outside camp by culturing specimens from noncamper control subjects with cystic fibrosis who were known not to be infected < or = 2 weeks before and 4 to 6 weeks after camp. We also determined the risk factors for P. cepacia acquisition by determining the relative risk of acquisition between campers who were exposed versus campers who were not exposed to campers known to be infected or to potential environmental sources of P. cepacia at camp. The ribotype of P. cepacia isolates from campers with sputum conversion was compared with that of isolates from other campers and from an environmental source. The cumulative incidence of sputum conversion during the study period was 6.1% (11/181) among campers compared with no incidence (0/92) among noncampers (p = 0.02, Fisher Exact Test). The incidence of sputum conversion at camp varied according to the prevalence of campers with known infection (p < 0.001, chi-square test for trend). The rate of sputum conversion was higher in the camp with longer duration (relative risk = 12.0; 95% confidence interval = 2.7 to 53.5). Ribotyping showed that P. cepacia isolates from all 11 campers with sputum conversion were identical or similar (1 to 2 band difference) to isolates of other P. cepacia-infected campers including co-converters. These results suggest that P. cepacia can be acquired by patients with cystic fibrosis who are attending summer camp for such patients, possibly through person-to-person transmission, and that the risk increases with the prevalence of P. cepacia-infected campers and the duration of camp.

Aspergillus fumigatus sternal wound infections in patients undergoing open heart surgery.

During a 21-month period (July 1986-April 1988), six patients who underwent open heart surgery at Holston Valley Hospital and Medical Center in Kingsport, Tennessee, developed sternal would infections caused by Aspergillus fumigatus. All patients required sternectomy, reconstructive surgery, and long term amphotericin B therapy; no patient died. By univariate analysis, the following were significantly associated with A. fumigatus sternal would infection: chronic lung disease, a recent history of pneumonia, a greater mean number of admission diagnoses, and a particular surgeon. However, multivariate analysis identified chronic lung disease as the only independent risk factor and the best predictor of A. fumigatus sternal wound infections. No factors related to the surgical procedure or operating room personnel were associated with infection. A review of the characteristics of the patients undergoing open heart surgery showed that since 1985, there had been a trend for these patients at Holston Valley Hospital and Medical Center to be older and sicker, which may have contributed to the occurrence of infections never observed before. Despite an extensive investigation, no environmental source for A. fumigatus was identified. A. fumigatus, however, grew from the bronchial washing of one patient at the time the sternal wound infection was diagnosed, and a prospective study showed that the rate of A. fumigatus colonization among open heart surgery patients was the same as the rate of sternal wound infections caused by A. fumigatus. These data suggest that patients with chronic lung disease and respiratory colonization with A. fumigatus are at increased risk for A. fumigatus sternal wound infections after open heart surgery.

Mycobacterium gordonae pseudoinfection associated with a contaminated antimicrobial solution.

At Yale-New Haven Hospital, 46 specimens submitted for mycobacterial culture during an 8-week period in 1989 were positive for Mycobacterium gordonae, a nontuberculous acid-fast bacterium (AFB) of low pathogenicity. The specimens were submitted from 34 patients who came from various inpatient and outpatient services. Four patients were begun on antimycobacterial therapy on the basis of an AFB isolate which was later identified as M. gordonae. Isolation of M. gordonae was associated with use of the BACTEC TB system (BACTEC TB; Becton Dickinson Diagnostic Instrument Systems, Towson, Md.) and an antimicrobial solution, BACTEC PANTA PLUS (PANTA; Becton Dickinson Diagnostic Instrument Systems). The manufacturer reported that two lots (B9K1 and C9K1) of PANTA kits containing a single production lot (N8C1) of PANTA, which had been shipped to 173 laboratories, had been contaminated with M. gordonae. A survey of mycobacteriology laboratories in the United States revealed that, during April to July 1989, the M. gordonae isolation rate was 5.8/1,000 AFB specimens processed at laboratories that did not use BACTEC TB, 11.4/1,000 AFB specimens at laboratories that used BACTEC TB but not the implicated lot of PANTA, and 23.5/1,000 AFB specimens at laboratories that used BACTEC TB and the lot of implicated PANTA. Intrinsic contamination of PANTA was attributed to ineffective sterilization of water used in the manufacturing process and was not detected prior to product shipment because cultures for AFB were not part of the quality control regimen. This episode emphasizes that clinical laboratories can detect pseudoepidemics promptly if they are alert to abrupt increases in isolation rates, especially of unusual or generally nonpathogenic organisms.

Characteristics of left-sided endocarditis due to Pseudomonas aeruginosa in the Detroit Medical Center.

Mortality due to left-sided endocarditis caused by Pseudomonas aeruginosa remains high despite the therapeutic regimen of high doses of an aminoglycoside plus a beta-lactam antibiotic. In this series, left-sided pseudomonal endocarditis presented as an acute illness refractory to optimal antibiotic therapy. Complications associated with active valvular infection, such as neurologic sequelae, ring and annular abscesses, congestive heart failure, and splenic abscesses, are frequent. The overall morbidity and mortality remain high; however, outcome appears to improve with surgery. Our present data suggest that early valve replacement accompanied by a 6-week course of high doses of a combination of drugs may be the optimal therapy for left-sided pseudomonal endocarditis. This approach not only may prevent serious and potentially lethal complications of the disease but also may cure them.

Comparative evaluation of selective media for isolation of Pseudomonas cepacia from cystic fibrosis patients and environmental sources.

Pseudomonas cepacia has recently emerged as an important pathogen affecting cystic fibrosis (CF) patients. We evaluated three selective media to assess their comparative potential for identification of patients colonized with P. cepacia and for efficacy of detection of P. cepacia in environmental fluids. Test organisms included P. cepacia isolates from CF patients (10 each from two CF centers), non-CF patients (10 isolates), and environmental sources (10 isolates). Microbiologic assays were done by the membrane filter procedure; filters were placed on P. cepacia medium (PCM), OFPBL, TB-T, MacConkey agar (MAC), and blood agar (BA) or Standard Methods (SM) sugar, and colonies were counted after incubation at 30 or 35 degrees C for 72 h. Mean recovery efficiencies (MREs) (mean CFU/ml on selective media compared with CFU/ml on BA controls) for environmental and non-CF P. cepacia and patient isolates from one CF center showed a rank order of PCM greater than OFPBL greater than TB-T; for isolates from a second CF center, a rank order of PCM greater than TB-T greater than OFPBL was obtained. MREs for CF center isolates were generally lower than for non-CF patients or environmental isolates on P. cepacia-selective media. With MAC, the MREs for each group of CF isolates were extremely low (14 and 2%) compared with those for non-CF patient (47%) or environmental (84%) isolates. In laboratory and field studies, PCM and OFPBL showed good selectivity against bacteria commonly associated with CF patient respiratory secretions. These findings show that selective media should be used in clinical settings where P. cepacia is sought. With environmental fluids from CF centers, P. cepacia-selective media showed low selectivity against a variety of gram-negative water bacteria and appeared to afford little advantage over SM agar for isolating P. cepacia from environmental samples.

The epidemiology of Pseudomonas cepacia in patients with cystic fibrosis.

Pseudomonas cepacia has emerged as an important nosocomial pathogen colonizing and infecting the respiratory tract of patients with cystic fibrosis (CF). Although assessment of outcomes associated with P. cepacia colonization has been difficult, controlled studies have shown that colonized patients experience more adverse outcomes compared with those not colonized. In the United States, an increasing trend in national incidence and prevalence of P. cepacia colonization has been shown, but cases have been unevenly distributed in a few centers. These estimates, however, may be biased by intercenter differences in laboratory methods for detecting P. cepacia in patient sputum. The source and mode of transmission of P. cepacia have not been adequately demonstrated, and may vary from center to center. Until further studies elucidate the epidemiology of P. cepacia in patients with CF, it may be prudent for CF centers to consider the use of selective media to isolate P. cepacia from sputa of patients with CF, to conduct investigations of clusters of P. cepacia-colonized patients, and to consider adopting infection control precautions recommended for control of multiply resistant gram negative organisms.

The epidemiology of nosocomial epidemic Pseudomonas cepacia infections.

Pseudomonas cepacia has occasionally been identified as an epidemic and endemic nosocomial pathogen. In outbreaks, usually one clinical site predominates but many may be involved. Detailed investigations have usually implicated a contaminated liquid reservoir or moist environmental surface as the source. Liquid sources have included a number of different classes of antiseptics and disinfectants such as quaternary ammonium chlorides, biguanides, hexachlorophene, and iodophors. Environmental and patient isolates have had multiply resistant antimicrobial susceptibility patterns. The clinical distinction between colonization and infection may be difficult and may challenge the skills of the clinician. Expenditure of resources needed to solve epidemics is justified in view of the potential virulence of this organism and the high likelihood that an unrecognized but easily eliminated liquid environmental reservoir may be the source.

Colonization of the respiratory tract with Pseudomonas cepacia in cystic fibrosis. Risk factors and outcomes.

Between 1981 and 1983, some 85 patients with cystic fibrosis at Rainbow Babies and Childrens Hospital, Cleveland, developed colonization or infection of the respiratory tract with Pseudomonas cepacia. Twenty-nine (34 percent) of the colonized patients died; four were female patients with fulminant bacteremia with P cepacia prior to death. Case-control studies showed that increasing severity of underlying cystic fibrosis, increasing age, having a sibling with cystic fibrosis who was colonized with P cepacia, and previous hospitalizations were associated with increased risk of colonization. In patients with mild cystic fibrosis, no differences in clinical outcome were seen during the period of study; however, patients colonized with P cepacia who had moderate or advanced cystic fibrosis were hospitalized longer and died sooner after colonization, compared with control subjects with similar severity of cystic fibrosis. The excess mortality associated with such colonization varied in magnitude and trend according to the patient's sex and severity of underlying cystic fibrosis, reflecting the combined influence of colonization with P cepacia, sex, and severity of cystic fibrosis on the mortality of the patients. The source and mode of transmission of P cepacia were not determined, but the data suggest a possible nosocomial source. The results of this investigation showed that colonization with P cepacia most often affected patients with moderate or advanced cystic fibrosis and was associated with an adverse clinical outcome in these patients.

Laboratory proficiency test results on use of selective media for isolating Pseudomonas cepacia from simulated sputum specimens of patients with cystic fibrosis.

Pseudomonas cepacia colonization of or infection in patients with cystic fibrosis (CF) has been associated with increased morbidity and premature death. However, current data on national incidence may be biased because of interlaboratory differences in the methods of culturing sputa of patients with CF. We conducted three tests to evaluate the proficiency of microbiology laboratories at CF centers in identifying and isolating P. cepacia and to assess the value of using selective media for P. cepacia (P. cepacia agar and oxidation-fermentation polymyxin-bacitracin-lactose medium [OFPBL]) to recover P. cepacia from specimens simulating sputa of patients with CF. In test 1, we evaluated the proficiency of laboratories in identifying P. cepacia. Of 111 laboratories tested, 105 (95%) correctly identified P. cepacia. In test 2, we evaluated the proficiency of laboratories in isolating P. cepacia from simulated CF sputum specimens. Only 36 (32%) of 115 laboratories detected P. cepacia. Recovery of the microorganism was associated with the use of P cepacia agar or OFPBL; 14 (95%) of 15 laboratories using P. cepacia agar or OFPBL (or both) versus 22 (22%) of 100 laboratories not using either medium recovered P. cepacia (P less than 0.0001, Fisher exact test, one tailed). Laboratories failing test 2 were requested to use a selective medium for P. cepacia in a repeat test; 73 (97%) of 75 laboratories using P. cepacia agar or OFPBL (or both) versus 0 of 4 laboratories not using either medium detected P. cepacia (P less than 0.0001, Fisher exact test, one tailed). Our studies show that (i) microbiology laboratories at CF centers are proficient in identifying P. cepacia, and (ii) the use of selective media for P. cepacia enhances recovery of the microorganism in simulated sputum specimens. Therefore, we recommend the use of selective media for P. cepacia in laboratories processing sputa of patients with CF.

Construction activity: an independent risk factor for invasive aspergillosis and zygomycosis in patients with hematologic malignancy.

Between November 1982 and July 1984, five patients at a 110-bed pediatric hospital were diagnosed with invasive filamentous fungal infection; three had invasive aspergillosis (IA) and two had invasive zygomycosis (IZ). All five had underlying hematologic malignancy (HM). In a case-control study, these five HM patients (cases) were compared to 10 autopsied HM patients without evidence of aspergillosis or zygomycosis (controls). Cases and controls did not differ in underlying disease or in the degree of immunosuppression, as measured by duration of granulocytopenia and number of platelet transfusions. However, case-patients were more likely than controls to have been hospitalized during the construction of a hospital addition (p less than 0.02, Fisher's exact test [FET]). Four (80%) of five HM patients autopsied during the period of construction had IA or IZ compared with one (5%) of 21 autopsied before construction began (p = 0.001, FET). These findings suggest that, in a population of comparably immunosuppressed patients, construction activity may represent an independent risk factor for IA or IZ. Hospitals caring for such patients should take precautions which minimize exposure of these patients to construction or renovation activity.

Pseudomonas cepacia colonization in patients with cystic fibrosis: risk factors and clinical outcome.

During the period of 1979 to 1983, 38 patients with cystic fibrosis (CF) at the CF center of St. Christopher's Hospital for Children in Pennsylvania developed respiratory tract colonization with Pseudomonas cepacia. Seventeen (45%) of the patients with colonization died. Yearly incidence rates of P. cepacia colonization fluctuated between 1.3% and 6.1%, suggesting an endemic phenomenon. Case-control studies showed that severe underlying CF, use of aminoglycosides, and having a sibling with CF and P. cepacia colonization were significant risk factors for P. cepacia colonization. Once colonized with P. cepacia, patients with CF were likely to be hospitalized longer (P = 0.008) and to die sooner (P = 0.0001) than control patients with CF. Environmental and microbiologic studies did not identify a common source or mode of transmission of P. cepacia among patients. The results of this investigation suggest that P. cepacia colonization of patients with CF was endemic in the hospital, occurred more frequently in those with severe disease, and was associated with adverse clinical outcome.

Chronic interstitial pulmonary fibrosis following Mycoplasma pneumoniae pneumonia.

An unusual case of chronic interstitial fibrosis that developed as a sequela of Mycoplasma pneumoniae pneumonia is described. Predominant manifestations included progressive exertional dyspnea, shortness of breath, persisting lung infiltrates, low lung volumes, and low pulmonary diffusing capacity. Open lung biopsy one year after the acute stage of mycoplasma pneumonia revealed focal interstitial fibrosis with early pleural thickening, hypertrophic alveolar lining cells, and peribronchiolar lymphoid cell infiltrates. Improvement in clinical manifestations, radiologic findings, and pulmonary function results occurred with steroid therapy.