Quasi-experimental study designs, often described as nonrandomized, pre-post intervention studies, are common in the medical informatics literature. Yet little has been written about the benefits and limitations of the quasi-experimental approach as applied to informatics studies. This paper outlines a relative hierarchy and nomenclature of quasi-experimental study designs that is applicable to medical informatics intervention studies. In addition, the authors performed a systematic review of two medical informatics journals, the Journal of the American Medical Informatics Association (JAMIA) and the International Journal of Medical Informatics (IJMI), to determine the number of quasi-experimental studies published and how the studies are classified on the above-mentioned relative hierarchy. They hope that future medical informatics studies will implement higher level quasi-experimental study designs that yield more convincing evidence for causal links between medical informatics interventions and outcomes.

Although a growing number of studies have found a relationship between delayed appropriate antibiotic therapy and mortality, few have attempted to quantify the temporal association between delayed appropriate antibiotic therapy and mortality. This study was designed to measure the elapsed time associated with an increased risk of 30-day mortality among patients with Pseudomonas aeruginosa bacteremia. The retrospective cohort study was conducted among immunocompetent, adult patients with P. aeruginosa bacteremia onset at least 2 days after hospital admission between 1 January 2001 and 30 September 2006. Classification and regression tree analysis (CART) was used to identify the delay in appropriate antibiotic therapy that was associated with an increased risk of 30-day mortality. During the study period, 100 patients met the inclusion criteria. The CART-derived breakpoint between early and delayed treatment was 52 h. The delayed treatment group experienced a >2-fold significant increase in 30-day mortality compared to the early treatment group (44 and 19%, respectively, P ‫؍‬ 0.008). Delayed appropriate therapy of >52 h (odds ratio [OR] ‫؍‬ 4.1; 95% confidence interval [CI] 1.2 to 13.9, P ‫؍‬ 0.03) was independently associated with 30-day mortality in the multivariate analysis. Antibiotic resistance >3 classes (adjusted OR [AOR] ‫؍‬ 4.6; 95% CI ‫؍‬ 1.9 to 11.2, P ‫؍‬ 0.001) and chronic obstructive pulmonary disease (AOR ‫؍‬ 5.4; 95% CI ‫؍‬ 1.5 to 19.7, P ‫؍‬ 0.01) were independently associated with delayed appropriate therapy of >52 h. The data strongly suggest that delaying appropriate therapy for approximately 2 days significantly increases the risk of 30-day mortality in patients with P. aeruginosa bloodstream infections.

Significantly higher rates of gram-negative infection were observed during the summer months, compared with other seasons. For some pathogens, higher temperatures were associated with higher infection rates, independent of seasonality. These findings have important implications for infection prevention, such as enhanced surveillance during the warmer months, and for choice of empirical antimicrobial therapy among hospitalized adults. Future, quasi-experimental investigations of gram-negative infection prevention initiatives should control for seasonal variation.

BackgroundThe high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.MethodsThis retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin.Results267 patients were included; 14% (38/267) received nafcillin or cefazolin, 51% (135/267) received both vancomycin and either nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin.ConclusionsReceipt of nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of nafcillin or cefazolin in the treatment of MSSA bacteremia.

Comorbidity is a known risk factor for antibiotic-resistant bacterial infections. Although aggregate comorbidity measures are useful in epidemiologic research, none of the existing measures was developed for use with this outcome. This study compared the utility of two comorbidity measures, the Charlson Comorbidity Index and the Chronic Disease Score, in assessing the comorbidity-attributable risk of nosocomial infections with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Two case-control studies were conducted at the University of Maryland Medical System in Baltimore, Maryland. Cases were inpatients with a first positive clinical culture of MRSA or VRE at least 48 hours postadmission (July 1, 1998-July 1, 2001). Three inpatient controls were randomly selected per case. The MRSA study included 2,164 patients, and the VRE study included 1,948. The scores' discrimination and calibration were measured by using the c statistic and Hosmer-Lemeshow chi-square test. The Charlson Comorbidity Index (c = 0.653) and Chronic Disease Score (c = 0.608) were similar discriminators of MRSA and VRE (c = 0.670 and c = 0.647, respectively). Calibration of the scores was poor for both outcomes (p < 0.05). A revised comorbidity measure specific to resistant infections would likely provide a better assessment of the comorbidity-attributable risk of antibiotic-resistant infections.

Studies of the association between inappropriate antibiotic therapy and mortality among bacteremic patients have generated conflicting findings. We systematically reviewed these studies to identify methodological heterogeneity that may explain the lack of agreement. We identified 51 articles that met the inclusion criteria, and we extracted the following data: study design, definition and measurement of variables, and statistical methods. Only 8 studies (16%) defined inappropriate antibiotic therapy as that which was inactive in vitro against the isolated organism(s) and not consistent with current clinical practice recommendations and distinguished between empiric and definitive treatment. Thirty-four studies (67%) measured the severity of illness, but only 6 (12%) specified the time at which it was measured. The methodological recommendations suggested in this article are intended to improve the validity and generalizability of future research. In brief, future studies should define "inappropriate" therapy on the basis of in vitro susceptibility data, should separately evaluate empiric and definitive therapy, and should control for the baseline severity of illness.

Accessory gene regulator (agr) dysfunction in Staphylococcus aureus has been associated with a longer duration of bacteremia. We aimed to assess the independent association between agr dysfunction in S. aureus bacteremia and 30-day in-hospital mortality. This retrospective cohort study included all adult inpatients with S. aureus bacteremia admitted between 1 January 2003 and 30 June 2007. Severity of illness prior to culture collection was measured using the modified acute physiology score (APS). agr dysfunction in S. aureus was identified semiquantitatively by using a ␦-hemolysin production assay. Cox proportional hazard models were used to measure the association between agr dysfunction and 30-day in-hospital mortality, statistically adjusting for patient and pathogen characteristics. Among 814 patient admissions complicated by S. aureus bacteremia, 181 (22%) patients were infected with S. aureus isolates with agr dysfunction. Overall, 18% of patients with agr dysfunction in S. aureus died, compared to 12% of those with functional agr in S. aureus (P ‫؍‬ 0.03). There was a trend toward higher mortality among patients with S. aureus with agr dysfunction (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 0.87 to 2.06). Among patients with the highest APS (scores of >28), agr dysfunction in S. aureus was significantly associated with mortality (adjusted HR, 1.82; 95% CI, 1.03 to 3.21). This is the first study to demonstrate an independent association between agr dysfunction and mortality among severely ill patients. The ␦-hemolysin assay examining agr function may be a simple and inexpensive approach to predicting patient outcomes and potentially optimizing antibiotic therapy.

Objective: Transmission of SARS-CoV-2 has significant implications for hospital infection prevention and control, discharge management, and public health. We reviewed available literature to reach an evidenced-based consensus on the expected duration of viral shedding. Design: We queried four scholarly repositories/search engines for studies reporting SARS-CoV-2 viral shedding dynamics by PCR and/or culture available through September 8, 2020. We calculated the pooled median duration of viral RNA shedding from respiratory and fecal sources. Results: Seventy-seven studies on SARS-CoV-2 were included. All studies reported PCR-based testing and 12 also included viral culture data. The overall pooled median duration of RNA shedding from respiratory sources was 18.4 days (95% CI: 15.5 days - 21.3 days; I2=98.87%, p<0.01) among 28 studies. When stratified by disease severity, the pooled median duration of viral RNA shedding from respiratory sources was 19.8 days (95% CI: 16.2 days – 23.5 days; I2=96.42%, p<0.01) among severely ill patients and 17.2 days (95% CI: 14.0 days - 20.5 days; I2=95.64%, p<0.01) in mild/moderate illness. Viral RNA was detected up to 92 days after symptom onset. Viable virus was isolated by culture from -6 days to 20 days relative to symptom onset. Conclusions: SARS-COV-2 RNA shedding can be prolonged, yet high heterogeneity exists. Detection of viral RNA may not correlate with infectivity since available viral culture data suggests shorter durations of shedding of viable virus. Additional data is needed to determine the duration of shedding of viable virus and the implications for risk of transmission.