Does sex affect 30-day mortality in Staphylococcus aureus bacteremia?

BACKGROUND: Sex-related differences in complications and mortality of infection were examined with conflicting results. Further studies are required to bring new light in this topic in Staphylococcus aureus infections. OBJECTIVE: We examined the outcomes of S. aureus infection in men and in women and whether sex-related differences were explained by underlying disorders, severity of disease, or clinical management. METHODS: This cohort study was conducted in a single center between 1988 and 2007. Patients with clinically significant S. aureus bacteremia were included. We compared 30-day all-cause mortality in men and women. We used multivariable logistic regression analysis to test whether sex was independently associated with mortality. RESULTS: One thousand ninety-three patients were identified with S. aureus bacteremia. All-cause mortality at day 30 was 39.3% (508 of 1293 patients): 44.8% (238 of 531 patients) in women and 35.4% (270 of 762 patients) in men (P < 0.01). In a multivariate analysis, female sex was associated with higher mortality (odds ratio = 1.63; 95% CI, 1.07-2.47). The excess mortality in women was not explained by differences in demographic characteristic factors, background conditions, infection severity and management, or septic complications. CONCLUSIONS: We found that women with S. aureus bacteremia had a greater risk of 30-day all-cause mortality than men, even when adjusting for other risk factors. However, we failed to explain this excess of mortality.

Looking beyond polypharmacy: quantification of medication regimen complexity in the elderly.

BACKGROUND: Polypharmacy has been shown to influence outcomes in elderly patients. However, the impact of medication regimen complexity, quantified by the Medication Regimen Complexity Index (MRCI), on health outcomes after discharge of elderly patients has not been studied. OBJECTIVE: Our aim was to test the convergent, discriminant, and predictive validity of the MRCI in older hospitalized patients with varying functional and cognitive levels. METHODS: We retrospectively applied the MRCI to the medication regimen of 212 hospitalized patients and assessed its validity. RESULTS: The mean (SD) MRCI scores for medication regimens and number of medications at discharge were 30.27 (13.95) and 5.95 (2.40), respectively. The MRCI scores were strongly correlated with the number of medications (r=0.94, P<0.001) and the number of daily doses (r=0.87, P<0.001) and increased as the number of medications taken ≥3 times daily increased (27.35, 34.45, and 43.00 for none, 1, and 2 drugs, respectively; P<0.001). Positive correlations were observed between the Cumulative Illness Rating Scale-Geriatrics score and both the number of medications and the MRCI score (r=0.40, r=0.46, P<0.001, respectively). No relationship was found between MRCI scores and the number of medications and age, sex, and postdischarge medication modifications. Patients nonadherent to at least 1 drug were discharged with a higher MRCI score and higher number of medications compared with medication-compliant patients (33.3 and 7.0 vs 27 and 5.8, respectively; P<0.01). An inverse correlation was found between overall adherence 1 month after discharge and the MRCI score (r=-0.188, P= 0.028); however, no such correlation was found regarding the number of medications at discharge. CONCLUSIONS: The MRCI showed satisfactory validity and good evidence of classifying regimen complexity over a simple medication count. The MRCI demonstrated application in clinical research and practice in the elderly. However, more studies are needed to investigate its advantage over the number of medications for identifying patients with complex medication regimens and directing interventions to simplify their medication regimen complexity.

Healthcare-associated vs. hospital-acquired Staphylococcus aureus bacteremia.

OBJECTIVE: To analyze clinical features and outcomes of patients with hospital-acquired (HA) and healthcare-associated (HCA) Staphylococcus aureus bacteremia. METHODS: A retrospective cohort study was conducted from 1988 to 2007. We compared patients with clinically significant HA with those with HCA S. aureus bacteremia. Risk factors for 30-day all-cause mortality were assessed using multivariable logistic regression analysis. Cox regression analysis was used to estimate the hazard ratio (HR) for 5-year mortality with 95% confidence intervals (CI). RESULTS: Of 1261 episodes, 735 (58.3%) were HA and 526 (41.7%) were HCA. The percentage of MRSA was 48.2% (354/735) in HA vs. 42.2% (222/526) in HCA bacteremia; p=0.04. The percentages of HCA S. aureus bacteremia and MRSA bacteremia did not vary throughout the study period. Mortality at 30 days was 40.2% (507/1261) and at 1 year was 63.4% (800/1261); this was comparable for HA and HCA bacteremia. Five-year survival curves in both settings followed very similar patterns (HR 1.01, 95% CI 0.89-1.15). Risk factors for 30-day mortality were similar, except for primary bacteremia and pre-existing heart valve disease in the HA group. CONCLUSIONS: HCA S. aureus bacteremia shares many similarities with HA bacteremia with respect to the prevalence of MRSA strains, mortality rates, and risk factors for death, and should be managed similarly.

Antibiotic prophylaxis in cardiac surgery: systematic review and meta-analysis.

BACKGROUND: Antibiotic prophylaxis is recommended in cardiac surgery. Current debate concerns the type of antibiotic(s), dosing and the duration of prophylaxis. METHODS: Systematic review of randomized controlled trials comparing one antibiotic regimen versus another in cardiac surgery. We searched The Cochrane Library, PubMed, LILACS, conference proceedings and bibliographies. Two reviewers independently extracted the data. The primary outcome was deep sternal wound infections (DSWIs). Meta-analysis was performed using the Mantel-Haenszel fixed-effect method. Risk ratios (RRs) with 95% confidence intervals (95% CIs) are reported. RESULTS: Fifty-nine trials were included. There were no significant differences in DSWI or all other categories of surgical site infections (SSIs) for antibiotic prophylaxis with ß-lactams comprising a Gram-negative spectrum of coverage versus prophylaxis targeting Gram-positive bacteria, but the former led to a significantly lower rate of post-operative pneumonia (RR 0.68, 95% CI 0.51-0.90) and all-cause mortality (RR 0.66, 95% CI 0.47-0.92). In trials comparing different antibiotic regimens for different durations, prophylaxis duration of ≤24 h post-operation led to higher rates of DSWI (RR 1.83, 95% CI 1.25-2.66), any sternal SSI, surgical interventions for SSI and endocarditis compared with longer duration prophylaxis. There was no advantage of regimens lasting >48 h post-operation. In the comparison of glycopeptides versus ß-lactams, an advantage of glycopeptides was observed when comparators were given for similar duration and for ß-lactams when given for a longer duration than the glycopeptides. There was no significant advantage of high antibiotic dosing. CONCLUSIONS: Evidence supports second- or third-generation cephalosporins for cardiac surgery prophylaxis and points at a possible advantage of prophylaxis prolongation up to 48 h post-operatively.

Validity of the Medication-based Disease Burden Index compared with the Charlson Comorbidity Index and the Cumulative Illness Rating Scale for geriatrics: a cohort study.

BACKGROUND: Co-morbidity is common in older people. A co-morbidity index reduces coexisting illnesses and their severity to a single numerical score, allowing comparison with scores from other patients. Recently, the Medication-Based Disease Burden Index (MDBI) was developed. OBJECTIVE: The aim of the study was to assess the MDBI's validity in hospitalized elderly patients. METHODS: Clinical and demographic data and data on patients' medications on admission were obtained prospectively. Retrospectively, we applied the MDBI to the patients' medication regimens, determining their co-morbidity using the Charlson Comorbidity Index and Cumulative Illness Rating Scale for Geriatrics (CIRS-G). The MDBI's criterion validity was assessed against the Charlson and CIRS-G indices. Convergent and discriminant validities were also assessed. The MDBI's predictive validity was assessed by its ability to predict 3-month post-discharge readmissions or mortality compared with the Charlson and CIRS-G indices. RESULTS: MDBI scores were correlated with the Charlson and CIRS-G indices' scores (r = 0.44 and r = 0.37, respectively [p < 0.001]). MDBI, Charlson Comorbidity Index and CIRS-G scores were correlated with the number of drugs (r = 0.52, r = 0.34 and r = 0.40, respectively [p < 0.001]) and were the same in both sexes. No significant differences in MDBI scores were found between cognitively normal and impaired mental status (IMS) patients or between the functionally independent and partially/fully dependent patients. Charlson Comorbidity Index and CIRS-G scores were significantly lower in IMS patients and in dependent patients. The MDBI had no predictive ability for 3-month mortality but had good predictive power for a composite of 3-month mortality or readmissions (odds ratio [OR] 2.99 [95% CI 0.99, 9.03; p = 0.051]). However, CIRS-G and Charlson indices had good predictive ability for mortality (OR 1.50 [95% CI 1.22, 1.84; p < 0.001] and OR 2.06 [95% CI 1.40, 3.02; p < 0.001], respectively) and for a composite of 3-month mortality or readmissions (OR 1.24 [95% CI 1.11, 1.34; p < 0.001] and OR 1.39 [95% CI 1.12, 1.72; p = 0.003], respectively). CONCLUSIONS: The MDBI showed satisfactory criterion, convergent and discriminant validities and good predictive validity for mortality or readmission, but failed to differentiate between cognitive and functional patient groups. The MDBI should be investigated in larger studies to determine its validity in settings where medication data rather than diagnostic data are more readily available. In clinical practice with elderly patients, we recommend employing co-morbidity indices that are based on medical records, such as the Charlson Comorbidity Index and CIRS-G.

[Atosiban treatment for preterm labor--financial considerations and savings by implementing clinical guidelines].

INTRODUCTION: Preterm delivery is a significant cause of neonatal morbidity and mortality. Pregnant women, with symptoms and signs consistent with preterm labor, can be treated with various tocolytic drugs. Atosiban is one of many drugs indicated to arrest imminent preterm labor. Various studies show that the efficacy of atosiban is similar to other tocolytic drugs. The main advantage of atosiban is a relativeLy low incidence of adverse maternal reactions. Its considerable shortcoming is the financial cost, compared to other available drugs. AIM: In view of its cost, we have decided to implement a strict protocol to direct the use of atosiban, with the intent to reduce costs, without hampering quality of care. STUDY METHODS: The protocol was implemented from July 2009, and it outlines the medical and procedural terms to use atosiban. We compared similar time periods before and after implementation of the protocol. The outcomes compared included: treatment success, rates of preterm deliveries and financial costs. RESULTS: Within the timeframe that the protocol was implemented, we have been able to demonstrate a 40% reduction in atosiban related costs, compared to a parallel period, when the clinical guidelines were not implemented. This translates into savings of about NIS 40,000 (New Israeli Shekel) (approximately $10,000). This was achieved without an increase in the rate of preterm deliveries. CONCLUSION: Implementing and enforcing a simple protocol of supervision on the use of atosiban enables a considerable reduction of financial costs related to atosiban, without hampering medical care.

Thrombocytopenia in Staphylococcus aureus bacteremia: risk factors and prognostic importance.

OBJECTIVE: To identify risk factors and outcomes associated with thrombocytopenia at sepsis onset in Staphylococcus aureus bacteremia. PATIENTS AND METHODS: This single-center, retrospective, cohort study consists of all adult patients with a first episode of clinical S aureus bacteremia between April 1, 1988, and September 30, 1994, and between January 1, 1999, and December 31, 2007. Thrombocytopenia was defined as a platelet count less than 150 × 10(9)/L. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified using univariate and multivariable analyses. Multivariable analysis was conducted using forward step logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for risk of death. RESULTS: A total of 1052 patients had clinical S aureus bacteremia. Thrombocytopenia at sepsis onset was present in 235 patients (22.3%). Thrombocytopenia was associated with community-acquired bacteremia, infections caused by methicillin-sensitive S aureus, high-magnitude bacteremia (defined as >4 positive blood cultures [≥ 3 separate positive blood culture sets]), and endocarditis. Patients with thrombocytopenia presented more commonly with severe sepsis reflected by septic shock and acute renal failure. Thirty-day mortality was significantly higher among patients with thrombocytopenia (132/235 [56.2%]) vs those without thrombocytopenia (281/817 [34.4%]; P<.001). Higher mortality was associated with the degree of thrombocytopenia. In multivariable analysis, thrombocytopenia at baseline remained an independent risk factor for 30-day mortality (OR, 2.82; 95% CI, 1.87-4.24). The adjusted association between thrombocytopenia and death remained similar among the 917 patients with monomicrobial bacteremia (OR, 2.88; 95% CI, 1.83-4.53) and the 945 patients who did not die within the first 48 hours (OR, 2.88; 95% CI, 1.87-4.45.). CONCLUSION: We observed a strong association between thrombocytopenia at sepsis onset and all-cause mortality in S aureus bacteremia, possibly related to mechanisms other than sepsis alone.

PCR using blood for diagnosis of invasive pneumococcal disease: systematic review and meta-analysis.

The use of molecular-based methods for the diagnosis of bacterial infections in blood is appealing, but they have not yet passed the threshold for clinical practice. A systematic review of prospective and case-control studies assessing the diagnostic utility of PCR directly with blood samples for the diagnosis of invasive pneumococcal disease (IPD) was performed. A broad search was conducted to identify published and unpublished studies. Two reviewers independently extracted the data. Summary estimates for sensitivity and specificity with 95% confidence intervals (CIs) were calculated by using the hierarchical summary receiver operating characteristic method. The effects of sample processing, PCR type, the gene-specific primer, study design, the participants' age, and the source of infection on the diagnostic odds ratios were assessed through meta-regression. Twenty-nine studies published between 1993 and 2009 were included. By using pneumococcal bacteremia for case definition and healthy people or patients with bacteremia caused by other bacteria as controls (22 studies), the summary estimates for sensitivity and specificity were 57.1% (95% CI, 45.7 to 67.8%) and 98.6% (95% CI, 96.4 to 99.5%), respectively. When the controls were patients suspected of having IPD without pneumococcal bacteremia (26 studies), the respective values were 66.4% (95% CI, 55.9 to 75.6%) and 87.8% (95% CI, 79.5 to 93.1%). With lower degrees of proof for IPD (any culture or serology result and the clinical impression), the sensitivity of PCR decreased and the specificity increased. All analyses were highly heterogeneous. The use of nested PCR and being a child were associated with low specificity, while the use of a cohort study design was associated with a low sensitivity. The lack of an appropriate reference standard might have caused underestimation of the performance of the PCR. Currently available methods for PCR with blood samples for the diagnosis of IPD lack the sensitivity and specificity necessary for clinical practice.

Is there an association between inappropriate prescription drug use and adherence in discharged elderly patients?

BACKGROUND: Inappropriate prescription drug (IPD) use is very common among older patients. However, its impact on medication continuity and adherence after hospitalization has not been researched, with little known regarding readmissions and mortality. OBJECTIVE: To investigate the prevalence and clinical characteristics of patients discharged with IPDs and examine whether use of these drugs is related to medication continuity and adherence 1 month postdischarge as well as to readmissions and mortality 3 months postdischarge. METHODS: Clinical and demographic data, postdischarge medication modification, and adherence were prospectively obtained on interview of 212 unselected elderly (aged > or = 65 y) patients or, if necessary, their caregivers. Nonadherence was defined as the percentage of drug doses less than or equal to 70% or greater than or equal to 110%. Medication appropriateness was assessed retrospectively using the Beers' criteria. RESULTS: Use of IPDs occurred in 43.5% and 44.4% of patients on admission and discharge, respectively. At discharge, the numbers of IPDs and prescribed drugs were correlated (R = 0.39; p < 0.01). No relationship was found between IPDs at discharge and age, sex, functional and cognitive status, number of chronic diseases, and reason for admission. Sixty percent of patients who were nonadherent to at least one drug had at least one IPD, compared with 37.4% of the adherent patients (p = 0.008). Nonadherence to at least one drug increased as the number of IPDs on discharge increased (p = 0.004). No relationship was found between IPD use and postdischarge medication modifications, readmissions, and mortality. CONCLUSIONS: A high number of hospitalized elderly patients are discharged with IPDs that are directly correlated with the number of prescribed drugs at discharge and postdischarge nonadherence. Further studies are needed to assess the impact of postdischarge IPD use on health outcome, and healthcare providers should work to decrease its prevalence.

Continuity and adherence to long-term drug treatment by geriatric patients after hospital discharge: a prospective cohort study.

BACKGROUND: Increased life expectancy is associated with an increased prevalence of chronic diseases and drug consumption. Changes often occur in the medication regimen after hospitalization. The extent and nature of these changes and the adherence of elderly patients have not yet been fully investigated. OBJECTIVE: To investigate the extent and reasons for modifications to the medication regimens of elderly patients and their adherence to treatment during the first month following hospital discharge. METHODS: This was a prospective cohort study of 198 patients aged>or=65 years in the Acute Geriatric Ward, Beilinson Hospital, Rabin Medical Center, Israel. Clinical, demographic and medication regimen data were recorded for all patients at an interview conducted prior to discharge. After 1 month, the patient, caregiver or general practitioner (GP) were interviewed regarding the extent and reasons for modifications to the medication regimen and adherence to treatment. RESULTS: At 1-month post-discharge, on average, 36.7% of patient medications had been modified compared with the discharge prescription. No modification was found in 16% of patients. During the observation month, 62% of prescribed long-term medications were taken without modification as recommended at discharge and during follow-up, 50% of all changes were characterized by the addition of a drug or an increase in dosage, and 26%, 16% and 8% consisted of cancelling, omission or switching within the same medication type, respectively. Seventy percent of medication regimen changes were based on specialists' recommendations or secondary to a change in the patients' medical state, and 13%, 8%, 3% and 6% were as a result of poor adherence, adverse effects, administrative restrictions and other reasons, respectively. There was no correlation between medication regimen change and age, gender, physical function, cognitive function and length of hospital stay. Patients discharged home experienced less regimen modification than those discharged elsewhere (p=0.02). Patients who visited their GP only once experienced less regimen modification (p=0.03). Regression analysis showed that the only factors affecting medication regimen changes were GP visits and chronic diseases (p<0.01, R2=0.09). The overall mean adherence among 145 home-dwelling patients was 96.7%. Twenty-seven percent and 6% were under- and over-adherent, respectively, to at least one drug; under-adherence was more widespread than over-adherence. No correlation was found between the overall mean adherence and other clinical parameters or regimen change. However, non-adherence to at least one drug was associated with more medication regimen changes (p=0.001), was more common in patients discharged with prescriptions for seven or more drug types per day (p=0.01) and was associated with failing to visit the patient's GP 1 month after discharge (p=0.02). CONCLUSION: The majority of elderly patients experienced modifications in their medication regimen during the first month following hospital discharge. Thirty percent of patients were non-adherent to at least one drug. To improve adherence to a hospital medication regimen, patients should be encouraged to visit their GP and the number of long-term drugs should be reduced.

Relationship of in-hospital medication modifications of elderly patients to postdischarge medications, adherence, and mortality.

BACKGROUND: Medication regimens are constantly modified and updated during a patient's hospitalization. These modifications and those made after discharge might increase the risk for nonadherence, polypharmacy, and poor outcomes among elderly patients. OBJECTIVES: To investigate the extent of in-hospital modification of medication regimens of elderly patients and its relationship to medication adherence as well as one-month postdischarge drug regimen modifications and to examine the relationship of the modifications, adherence, and polypharmacy to mortality and readmissions 3 months postdischarge. METHODS: Clinical and demographic data, postdischarge medication modifications, and adherence were prospectively obtained in 212 elderly patients. Inhospital drug regimen modifications were retrospectively recorded. RESULTS: The average +/- SD in-hospital medication regimen modification rate was 49.8% +/- 28.4. No modifications were found in 9.7% of the patients. Using demographic and clinical parameters, we performed regression analysis and found that patients who were admitted with polypharmacy, discharged home, and cognitively normal experienced fewer medication modifications (p < 0.05). At one month postdischarge, the average medication regimen modification rate was 37.5% +/- 25.4. In- and posthospital modifications were directly correlated (p = 0.047). Three months postdischarge, 17 patients had died and 50 had been readmitted. The independent risk factors for mortality were in-hospital modification rate of 50% or greater (OR 6.4; 95% CI 1.3 to 29.7), impaired cognition (OR 4.2; 95% CI 1.4 to 12.3), and each chronic disease (OR 1.2; 95% CI 1 to 1.5). No relationships were found between in-hospital medication regimen modifications and readmissions or with postdischarge modifications, adherence, and polypharmacy to mortality and readmissions. CONCLUSIONS: Hospitalization of elderly patients is characterized by extensive medication regimen modifications, which are directly correlated with postdischarge modifications and may indicate an increased risk of mortality.