Case-control studies often analyze risk factors for antibiotic resistance. Recently published articles have illustrated that randomly selected control-patients may be preferable to those with the susceptible phenotype of the organism. A possible methodologic problem with randomly selected control-patients is potential bias due to control group misclassification. This occurs if some control-patients did not have clinical cultures performed and thus might have been unidentified case-patients. If this bias exists, these studies might be expected to report lower odds ratios (ORs) because control-patients would be more like case-patients.

To analyze potential biases that might arise due to control group misclassification and potentially larger selection biases that may be introduced if control-patients are required to have at least one clinical culture.

One hundred twenty case-patients, 770 control-patients in group 1, and 510 control-patients in group 2.

Two case-control studies. Case-patients had clinical cultures positive for imipenem-resistant Pseudomonas aeruginosa. The first group of control-patients were random. The second group of control-patients were identical to those in group 1 except being required to have at least one clinical culture.

Univariate analyses showed higher ORs for case-patients versus control-patients in group 1 (imipenem [OR, 12.5], piperacillin-tazobactam [OR, 3.7], and vancomycin [OR, 4.7]) as compared with case-patients versus control-patients in group 2 (imipenem [OR, 8.0], piperacillin-tazobactam [OR, 2.5], and vancomycin [OR, 3.0]).

Requiring control-patients to have at least one clinical culture introduces a selection bias likely because it eliminates patients with less severe illness.

There are significant limitations of the standard case-control study design for identifying risk factors for resistant organisms. The objective of this study was to develop a study design to overcome these limitations.

Theoretical analysis of different types of study designs that can be used in risk factor studies for resistant organisms.

We developed the case-case-control study design, which uses two separate case-control analyses within a single study. The first analysis compares patients infected with resistant bacteria (resistant cases) with control-patients without infection caused by the target organism, who are therefore representative of the source population; and the second analysis compares patients infected with the susceptible phenotype of the target organism (susceptible cases) with the same controlpatients without infection caused by the target organism. These two analyses provide risk models for (1) isolation of the resistant phenotype of the target organism as compared with the source population and (2) isolation of the susceptible phenotype of the organism as compared with the source population. When these two risk models are compared and contrasted, risk factors specifically associated with isolation of the resistant phenotype can be identified.

The case-case-control study design is an effective method for identifying risk factors for antimicrobial-resistant pathogens. Although the case-case-control study design has limitations, it is, in our opinion, more informative and less flawed than the standard case-control study design.

To evaluate the influence of matching on exposure time on estimates of attributable mortality of nosocomial bacteremia as assessed by matched cohort studies.

Two retrospective, pairwise-matched (1:2) cohort studies.

A 54-bed intensive care unit (ICU) in a university hospital.

Patients with nosocomial Escherichia coli bacteremia (n = 68) and control-patients without nosocomial bacteremia (n = 136 for each matched cohort study).

In both matched cohort studies, the same set of bacteremic patients was matched with control-patients using the APACHE II system. In the first study, control-patients were required to have an ICU stay at least as long as the respective bacteremic patient prior to onset of bacteremia (matching on exposure time). In the second study, control-patients were required to have an ICU stay shorter than the stay prior to the development of bacteremia in the respective bacteremic patient (no matching on exposure time).

For bacteremic patients, the mean ICU stay before onset of the bacteremia was 9 days (median, 6 days). In the first matched cohort study, hospital mortality was not different between bacteremic patients and control-patients (44.1% vs 43.4%; P = .999). In the second study, mortality of bacteremic patients and control-patients was also not different (44.1% vs 47.8%; P = .657). Mortality rates between control groups were not different (43.4% vs 47.8%; P = .543).

Matching or not matching on exposure time did not alter the estimate of attributable mortality for ICU patients with E. coli bacteremia.

To describe the epidemiology of nosocomial outbreaks published in the scientific literature.

Descriptive information was obtained from a sample of 1,022 published nosocomial outbreaks from 1966 to 2002.

Published nosocomial outbreaks of the most important nosocomial pathogens were included in the database. A structured questionnaire was devised to extract information in a systematic manner on nosocomial outbreaks published in the literature. The following items were used: the reference, type of study (case reports or studies applying epidemiologic or fingerprinting methods), type of microorganism, setting, patients and personnel involved, type of infection, source of infection, mode of transmission, risk factors identified, and preventive measures applied.

Bloodstream infection was the most frequently identified type of infection (37.0%), followed by gastrointestinal infection (28.5%) and pneumonia (22.9%). In 37% of the outbreaks, the authors were not able to identify the sources. The most frequent sources were patients (25.7%), followed by medical equipment or devices (11.9%), the environment (11.6%), and the staff (10.9%). The mode of transmission remained unclear in 28.3% of the outbreaks. Transmission was by contact in 45.3%, by invasive technique in 16.1%, and through the air in 15.0%. The percentage of outbreaks investigated by case-control studies or cohort studies over the years was small (21% and 9%, respectively, for the whole time period).

Outbreak reports in the literature are a valuable resource and should be used for educational purposes as well as for preparing outbreak investigations.

To date, it has not been adequately proven whether the published formulas used to obtain incidence from the prevalence of nosocomial infections provide a good estimate of real incidence. With the hypothesis that within the hospital setting prevalence may be lower than incidence, the aim of this study was to analyze the behavior of point prevalence as it relates to cumulative incidence and duration of infection.

Hospital simulation study.

By randomly selecting a sample of infected patients within a specific range of cumulative incidences and infection durations, we constructed a simulated hospital population, allowing us to estimate daily point prevalences and their maximum and minimum values. The association between the different components of stay and cumulative incidence was evaluated to obtain a more accurate estimate of incidence.

Prevalence can be lower than, equal to, or higher than the corresponding incidence. For all incidence levels, prevalence was increasing with duration. Between 14 and 20 days of infection duration, prevalence was consistently lower than incidence. Prevalence duration of infection was approximately half the time of the total duration.

The existing formulas relating incidence and prevalence can frequently be inadequate. Until a validated system for converting prevalence into incidence is available, we do not believe their use is appropriate.

To assess the value of repeated point-prevalence surveys in measuring the trend in nosocomial infections after adjustment for case mix.

A 3,500-bed teaching facility composed of 4 acute care hospitals.

From May 1992 to June 1996, eight point-prevalence surveys of nosocomial infections were performed in the hospitals using a sampling process. The trend of adjusted nosocomial infection rates was studied for the four surveys that collected data on indwelling catheters. Adjusted rates were calculated using a logistic regression model and a direct standardization method.

From 1992 to 1996, a total of 20,238 patients were included in the 8 point-prevalence surveys. The nosocomial infection rate decreased from 8.6% in 1992 to 5% in 1996 (P < .001). The analysis of adjusted nosocomial infection rates included 9,600 patients. Four independent risk factors were identified; length of stay greater than 12 days, hospitalization in an intensive care unit, presence of an indwelling urinary catheter, and history of a surgical procedure. After adjustment for case mix, the nosocomial infection rate still showed a downward trend (from 7.2% in 1993 to 5.1% in 1996; P = .02).

Adjusted prevalence rates of nosocomial infections showed a significant downward trend during the period of this study.

To compare ventilator-associated pneumonia (VAP) rates and patterns of isolates across studies of antibiotic and non-antibiotic methods for preventing VAP.

With the use of 42 cohort study groups as the reference standard, the prevalence of VAP was modeled in two linear regressions: one with the control groups and the other with the intervention groups of 96 VAP prevention studies. The proportion of patients admitted with trauma and the VAP diagnostic criteria were used as ecologic correlates. Also, the patterns of pathogenic isolates were available for 117 groups.

In the first regression model, the VAP rates for the control groups of antibiotic-based prevention studies were at least 18 (CI95, 12 to 24) per 100 patients higher than those in the cohort study groups (P < .001). By contrast, comparisons of cohort study groups with all other control and intervention groups in the first and second regression models yielded differences that were less than 6 per 100 and not significant (P > .05). For control groups with VAP rates greater than 35%, the patterns of VAP isolates, such as the proportion of Staphylococcus aureus, more closely resembled those in the corresponding intervention groups than in the cohort groups.

The rates of VAP in the control groups of the antibiotic prevention studies were significantly higher than expected and the patterns of pathogenic isolates were unusual. These observations suggest that inapparent outbreaks of VAP occurred in these studies. The possibility remains that antibiotic-based VAP prevention presents a major cross-infection hazard.

To apply two data mining algorithms (DMAs) to Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) reports that involved endotoxin-like reactions with intravenous gentamicin to determine whether a signal of disproportionate reporting of these events would have been generated concurrently with surveillance based on clinical observation.

Multi-item gamma-Poisson shrinker (MGPS) and proportional reporting ratios (PRRs) were used. Data used for data mining consisted of an extract of the FDA AERS database. Previously published details of clusters of endotoxin-like reactions to intravenous gentamicin were used to select adverse events for data mining.

The first signal of disproportionate reporting with any relevant event occurred in 1998, the year in which the outbreak was identified and evaluated by the Centers for Disease Control and Prevention and the FDA. In 1997, there were only 6 reports of rigors in the AERS; this jumped to 68 in 1998. In 1998, a signal was generated for endotoxic shock with PRRs but not with MGPS, based on one case.

The two DMAs generated signals concurrently with the influx of reports. It would have been difficult for safety reviewers to ignore an increase in rigors by traditional methods of safety surveillance; therefore, DMAs might not have had a great deal to offer in this instance. If data mining were considered as a second-line defense to diligent clinical observations under similar circumstances, simple disproportionality methods such as PRRs might be more useful than DMAs such as MGPS when commonly cited thresholds are used.

To determine whether randomly selected intravenous (IV) antimicrobial doses dispensed from an inpatient pharmacy were administered.

This was a prospective, cross-sectional study in which dose administration was confirmed by direct observation and by assessment of the medication administration record (MAR). A retrospective analysis of the return rate of unused IV antimicrobial doses was performed subsequently.

Medical and surgical intensive care units (ICUs) and non-ICUs of a 550-bed urban public teaching hospital.

Hospitalized patients with an order in the pharmacy database for an IV antimicrobial during 9 non-consecutive weekdays in June 1999.

Of 397 doses, 221 (55.7%) assessed by bedside observation and 238 (59.9%) assessed by MAR review were classified as administered; 139 doses (35.0%) were dispensed but changes in the drug order or the patient's status prevented their administration. In the subsequent assessment, of 745 IV antimicrobial doses dispensed during 24 hours, 322 (43.2%) were returned to the pharmacy unused; 423 (56.8%) of the doses—consistent with our prior observations—were presumably administered.

Because computerized pharmacy data may overestimate actual antimicrobial consumption, such data should be validated when used in studies of hospital antimicrobial use. Dispense-return analysis offers a simple validation method.

Respiratory tract infections significantly contribute to morbidity and mortality among cystic fibrosis (CF) patients. Therefore, pathogen transmission needs to be prevented. There are several guidelines for the care of CF patients, but no transparent systematic literature review has been published.

We conducted a systematic literature review (January 1966 to September 2004) dealing with segregation of CF patients colonized with Burkholderia cepacia species, Pandoraea species, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or Alcaligenes species. Quality of studies was evaluated by taking patient population size, existence of control-patients, patient randomization, diagnostic approach, and bacteria typing methods into account.

One hundred ninety-nine studies were found. Evidence and quality of 102 publications were evaluated. In 99 publications, recommendations concerning segregation measures for infectious CF patients were determined including a total of 11,576 patients. No randomized, controlled trials had been conducted. Fifty of 56 authors strongly recommended isolation of CF patients infected with B. cepacia or Pandoraea species. In 31 of 39 studies, interpatient spread of Pseudomonas aeruginosa was documented or had been brought to an end by isolation of patients. Only five studies had addressed S. maltophilia or Alcaligenes species.

Patients colonized with B. cepacia or Pandoraea species are to be separated from noncolonized patients in single rooms. Patients harboring multidrug-resistant Pseudomonas aeruginosa, S. maltophilia, or Alcaligenes species may not share a room with immunocompromised patients, in intensive care units, or with other CF patients anywhere in the hospital.

Formulating an effective approach to preventing surgeon-to-patient transmission of blood-borne pathogens has been controversial. The objective of our study was to evaluate current community hospital policies, if any, regarding restrictions on surgeons (general surgeons and obstetricians and gynecologists) infected with blood-borne pathogens operating on patients.

A survey on hospital policies regarding surgeons infected with blood-borne pathogens was sent to infection control officers at Northern California community hospitals (n = 113).

Forty-five hospitals responded to the survey. Of these, only 6 (13.3%) had a policy. Of the 39 (86.7%) that did not have a policy, only 3 hospitals were planning on implementing one.

Many community hospitals are uninterested in instituting a policy regarding the practice of surgeons infected with blood-borne pathogens. Possible reasons include the lack of concern on the individual level, difficulty in defining exposure-prone procedures, and the nature of the relationship between medical staff and community hospitals.