Prior statin use and 90-day mortality in Gram-negative and Gram-positive bloodstream infection: a prospective observational study

Mehl, Arne; Harthug, Stig; Lydersen, Stian; Paulsen, Julie; Åsvold, Bjørn Olav; Solligård, Erik; Damås, Jan Kristian; Edna, Tom-Harald

doi:10.1007/s10096-014-2269-6

Cited by 14 publications

(17 citation statements)

References 35 publications

(42 reference statements)

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“…Of particular note is that the majority of the studies reviewed so far did not adjust for the type of statin used or the type of bacteria causing the infection. An interesting study of the effect of prior statin use on mortality in patients with bloodstream infections found a significant reduction in 90-day mortality in statin users with Gram-negative infections (adjusted OR, 0.38; 95% CI, 0.20 to 0.72; P ϭ 0.003) but no significant difference in statin users with Gram-positive infections (adjusted OR, 1.22; 95% CI, 0.69 to 2.17; P ϭ 0.49) (36), suggesting that the type of bacterial infection may be a significant factor.…”

Section: Clinical Evidence That Statins Influence Morbidity and Mortamentioning

confidence: 97%

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

105

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bStatins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called "pleiotropic effects," which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and in vitro and in vivo virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents. O ne of the major undisputed clinical breakthroughs of the 20th century was the discovery of the statin family of drugs. These compounds are renowned for their ability to lower cholesterol levels and are used to treat approximately 40 million individuals with high cholesterol levels worldwide. Since the discovery of mevastatin as a metabolic product of Penicillium citrinum in 1976 (1, 2), a total of nine statins have been characterized, seven of which are approved by the FDA to treat patients with high cholesterol. Structurally, statins are characterized by the presence of a conserved lactone ring (3). This structure is present as a hydrolyzed (active) form in all statins except for mevastatin, lovastatin, and simvastatin; in those statins, the lactone ring is hydrolyzed in the liver (4). Statins can be divided into two broad classes (Fig. 1). Type 1 statins are lipophilic and possess a butyryl side chain-they are said to structurally resemble mevastatin (3). Lovastatin, pravastatin, and simvastatin are type 1 statins. Type 2 statins are classically lipophobic and are distinguished from type 1 by the replacement of the butyryl side chain with a fluorophenol group and typically possess larger side chains than type 1 statins (3). Atorvastatin, cerivastatin, fluvastatin, pitavastatin, and rosuvastatin are type 2 statins.Statins exert their cholesterol-lowering effect by binding to the active site of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR), a rate-limiting enzyme involved in cholesterol biosynthesis (3). HMGR is an integral part of the mevalonate pathway, which not only is essential for cholesterol biosynthesis but also contributes to the production of isoprenoids, lipid compounds that are essential for cell signaling and structure. As well as inhibition of cholesterol, statins have also been found to have a number of cholesterol-independent, socalled "pleiotropic" effects. Statins have been reported to confer anti-inflammatory, immunomodulatory, and anticancer effects on host cells, and these effects are well characterized (5-9). Furthermore, several studies have explored the pleiotropic effects of statins in combating multisystem microbial infections, such as sepsis and pneumonia, and a growing number of studies are demonstrating that statins can directly influence the growth and virulence of bacterial pathogens. With the global increase in antibiotic resistance to existing antib...

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Section: Clinical Evidence That Statins Influence Morbidity and Mortamentioning

confidence: 97%

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

105

View full text Add to dashboard Cite

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“…Case fatality rate was measured as all-cause mortality within day 30 and 90. By using the 11-digit unique identification number of all Norwegian citizens, electronic hospital records in Norway are updated with mortality data from the Norwegian population registry so that mortality data after discharge from hospital can be reliably assessed [ 21 , 22 ].…”

Section: Patient Characteristicsmentioning

confidence: 99%

Epidemiology and outcome of sepsis in adult patients with Streptococcus pneumoniae infection in a Norwegian county 1993–2011: an observational study

et al. 2016

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BackgroundInvasive pneumococcal disease (IPD) is responsible for significant mortality and morbidity worldwide. There are however few longitudinal studies on the changes in case fatality rate of IPD in recent years. We carried out a prospective observational study of patients with IPD in Nord Trøndelag county in Norway from 1993 to 2011 to study the clinical variables and disease outcome. The main outcome was all-cause mortality after 30 and 90 days.MethodsPatients with positive blood cultures were registered prospectively by the microbiology laboratory and clinical variables were registered retrospectively from patients’ hospital records. The severity of sepsis was assigned according to the 2001 International Sepsis Definition Conference criteria. The association between mortality and predictive factors was studied using a logistic regression model.ResultsThe total number of patients was 414 with mean age of 67 years and 53 % were male. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). A CCI-score of 0 was registered in 144 patients (34.8 %), whereas 190 had a score of 1–2 (45.9 %) and 80 (19.3 %) had a score ≥3. 68.8 % of the patients received appropriate antibiotics within the first 6 h. The 30-day mortality risk increased by age and was 3-fold higher for patients aged ≥80 years (24.9, 95 % CI 16.4–33.4 %) compared to patients aged <70 (8.0, 95 % CI 3.5–12.4 %). 110 patients, (26.6 %) had severe sepsis and 37 (8.9 %) had septic shock. The 30 day all-cause mortality risk for those with sepsis without organ failure was 5.4 % (95 % CI 2.7–8.0 %), 20.2 % (95 % CI 13.5–27.4 %) for those with severe sepsis and 35.0 % (95 % CI 21.6–49.0 %) for those with septic shock. The mortality risk did not differ between the first and the second halves of the study period with a 30-day mortality risk of 13.5 % (95 % CI 7.9–19.2 %) for 1993–2002 versus 11.8 % (95 % CI 8.2–15.3 %) for 2003–2011.ConclusionIPD carries a high mortality despite early and appropriate antibiotics in most cases. We found no substantial decrease in case fatality rate during the study period of 18 years. Older age and higher severity of disease were important risk factors for death in IPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1553-8) contains supplementary material, which is available to authorized users.

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“…Since 1994 the Mid-Norway Sepsis Study has continuously prospectively registered patients with confirmed BSI identified by growth of one or more microbes from blood culture, combined with clinical evidence of systemic infection [ 8 ]. A new occurrence of BSI was recorded for patients if at least 30 days had passed since a previous incident [ 9 ].…”

Section: Methodsmentioning

confidence: 99%

“…A new occurrence of BSI was recorded for patients if at least 30 days had passed since a previous incident [ 9 ]. Clinical information from the patients’ records was recorded retrospectively, after standardized definitions, by a team of trained health care professionals for all patients admitted before 2014 [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…The variables were categorized as follows: the observation-rate of each vital sign the first 24 hours after drawing a blood culture (temperature, respiratory frequency or heart rate) was graded as poor (0 or 1 recorded observation), some (2–4 recorded observations) or good observation (≥5 recorded observations); sepsis at admission as BSI without signs of SIRS, sepsis, severe sepsis, or septic shock [ 6 ]; sepsis-related Sequential Organ Failure Assessment (SOFA score) [ 11 ] at baseline and during follow up was dichotomized as non-severe or severe organ failure (corresponding to infection-related SOFA score >2 in any organ) [ 8 ]; infection focus as lungs, urinary tract, and other origin; BSI-type as gram-negative, gram-positive, and mixed microbial BSI (Additional file 2 ); length of stay (LOS) in the HDU and ICU and survival were counted in days, 0–24 hours was coded as 1 day, >24–48 hours as 2 days and so forth. All patients were censored after 30 days of observation; age (in years) at the time of positive blood culture was treated as a continuous variable and as a categorical variable (<65 years, 65–79 years, and >80 years); McCabe score was used to exclude patients with rapidly fatal illness at admission (death expected within 1 month) [ 12 ]; the Charlson weighted Comorbidity Index (CCI) was classified as low (no underlying disease score), medium (score 1–2), or high (score >2) [ 13 ]; place of acquisition was categorized as hospital-acquired if a positive blood culture was drawn >48 hours after admission, healthcare-associated (HCA) or community-acquired as defined by Friedman et al [ 14 ], with the exception that HCA infection was defined for patients hospitalized for ≥2 days in the last 30 days (instead of the last 90) before admission, as recommended by Schorr et al [ 15 ]; functional status was categorized as independent if the patient lived at home without any help from the community health service, partly independent if the patient had some help from the community health service, e.g., with medication or wound care, and dependent if the patient lived in a nursing home or lived at home with help in most of the daily life activities [ 8 ]; appropriate empiric antibiotic therapy was defined if (1) given intravenously in correct doses within 24 hours after the blood culture and (2) active in vitro against the isolated microbe(s) [ 16 ]; intravenous fluid was documented as amount in mL given during the first 24 hours after diagnosis.…”

Section: Methodsmentioning

confidence: 99%

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Early identification of sepsis in hospital inpatients by ward nurses increases 30-day survival

et al. 2016

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BackgroundSystemic inflammatory response syndrome (SIRS) and sepsis are now frequently identified by observations of vital signs and detection of organ failure during triage in the emergency room. However, there is less focus on the effect on patient outcome with better observation and treatment at the ward level.MethodsThis was a before-and-after intervention study in one emergency and community hospital within the Mid-Norway Sepsis Study catchment area. All patients with confirmed bloodstream infection have been prospectively registered continuously since 1994. Severity of sepsis, observation frequency of vital signs, treatment data, length of stay (LOS) in high dependency and intensive care units, and mortality were retrospectively registered from the patients’ medical journals.ResultsThe post-intervention group (n = 409) were observed better and had higher odds of surviving 30 days (OR 2.7, 95 % CI 1.6, 4.6), lower probability of developing severe organ failure (0.7, 95 % CI 0.4, 0.9), and on average, 3.7 days (95 % CI 1.5, 5.9 days) shorter LOS than the pre-intervention group (n = 472).ConclusionsIn a cohort with stable mortality rates, early sepsis recognition by ward nurses may have reduced progression of disease and improved survival for patients in hospital with sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1423-1) contains supplementary material, which is available to authorized users.

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Prior statin use and 90-day mortality in Gram-negative and Gram-positive bloodstream infection: a prospective observational study

Cited by 14 publications

References 35 publications

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Epidemiology and outcome of sepsis in adult patients with Streptococcus pneumoniae infection in a Norwegian county 1993–2011: an observational study

Early identification of sepsis in hospital inpatients by ward nurses increases 30-day survival

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