Predictive factors of septic shock and mortality in neutropenic patients

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.     

An outbreak of infections caused by strains of Staphylococcus aureus resistant to methicillin and aminoglycosides. I. Clinical studies.

In a 22-month period, strains of Staphylococcus aureus resistant to methicillin and multiple aminoglycosides, (designated MARS) were recovered from 108 inpatients with nosocomial infections at a hospital in the midwestern United States. Sixty-six of these patients were staying in a burn unit, and 42 were on other hospital wards. Among the patients with burns, MARS were recovered from the burn wounds of 64%; 32% of the patients with burns had MARS bacteremia. The patients without burns were age-matched with patients with nosocomial infections caused by antibiotic-susceptible strains of S. aureus. Patients from whom MARS were isolated had a longer mean hospital stay (79.6 days vs. 36.9 days; P less than 0.01), developed infection later (26.5 days vs. 13.5 days after admission; P less than 0.01), and had received antibiotic therapy before infection more often (81% vs. 38% of patients; P less than 0.01) than patients in the comparative population. Types of infection and incidences of death and bacteremia were similar in the two groups. Antibiotic-resistant strains of S. aureus may cause serious infections and significant mortality.     

A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance

Our objectives were to determine the incidence of endocarditis in patients whose Staphylococcus aureus bacteremia was community-acquired, related to hemodialysis, or hospital-acquired; to assess clinical factors that would reliably distinguished between S. aureus bacteremia and S. aureus endocarditis; to assess the emergence of methicillin-resistant S. aureus (MRSA) as a cause of endocarditis; and to examine risk factors for mortality in patients with S. aureus endocarditis.We conducted a prospective observational study in 6 university teaching hospitals; we evaluated 505 consecutive patients with Staphylococcus aureus bacteremia. Thirteen percent of patients with S. aureus bacteremia were found to have endocarditis, including 21% with community-acquired S. aureus bacteremia, 5% with hospital-acquired bacteremia, and 12% on hemodialysis. Infection was due to MRSA in 31%.Factors predictive of endocarditis included underlying valvular heart disease, history of prior endocarditis, intravenous drug use, community acquisition of bacteremia, and an unrecognized source. Twelve patients with bacteremia had a prosthetic valve; 17% developed endocarditis. Unexpectedly, nonwhite race proved to be an independent risk factor for endocarditis by both univariate and multivariate analyses. Persistent bacteremia (positive blood cultures at day 3 of appropriate therapy) was identified as an independent risk factor for both endocarditis and mortality, a unique observation not reported in other prospective studies of S. aureus bacteremia.Patients with endocarditis due to MRSA were significantly more likely to have complicating renal insufficiency and to experience persistent bacteremia than those with endocarditis due to MSSA. The 30-day mortality was 31% among patients with endocarditis compared to 21% in patients who had bacteremia without endocarditis (p = 0.055). Risk factors for death due to endocarditis included severity of illness at onset of bacteremia (as measured by Apache III and Pitt bacteremia score), MRSA infection, and presence of atrioventricular block on electrocardiogram.Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis. We recommend that blood cultures be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia. Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases. MRSA as the infecting organism should be added to the list of risk factors for consideration of valvular resection in cases of endocarditis.     

Predicting methicillin resistance and the effect of inadequate empiric therapy on survival in patients with Staphylococcus aureus bacteremia

BACKGROUND: The restriction of vancomycin hydrochloride use is recommended as a measure to decrease the emergence of vancomycin resistance in gram-positive organisms; however, vancomycin also is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections. If vancomycin use is restricted to patients with documented infections due to methicillin-resistant organisms, then patients with MRSA infections may not initially receive vancomycin. This study was performed to determine factors that predict MRSA bacteremia and if ineffective empiric antibiotic therapy increased the risk of death in patients with S aureus bacteremia. METHODS: We conducted a retrospective cohort study of all patients with clinically significant S aureus bacteremia (132 episodes in 128 patients) diagnosed between October 1, 1995, and January 1, 1998, at an urban acute care Veterans Affairs medical center (approximately 200 acute care beds) in Baltimore, Md. During the study period, vancomycin was a restricted antibiotic. Empiric use had to be approved by an attending physician specializing in infectious diseases. RESULTS: Compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly older (70 vs 58 years; P<.01), more likely to have a history of MRSA (47% vs 6%; P<.01) and a nosocomial infection (76% vs 50%; P<.01), and less likely to use injection drugs (8% vs 32%; P<.01). In addition, compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly less likely (45% vs 98%; P<.01) to receive effective antibiotic therapy during the first 48 hours of hospitalization. However, the risk of death due to ineffective empiric therapy was less than 1 (relative risk, 0.82; 95% confidence interval, 0.36-1.88) and did not change significantly when adjusted for age, occurrence of sepsis, or nosocomial infection. CONCLUSIONS: The results of this study support the safety of the restriction of vancomycin use in patients with clinically significant S aureus bacteremia. However, patients with a history of MRSA are more likely to have future MRSA infections and should receive empiric therapy using vancomycin for possible S aureus infections, particularly for nosocomial infections.     

Hospital mortality for patients with bacteremia due to Staphylococcus aureus or Pseudomonas aeruginosa

STUDY OBJECTIVES: To evaluate the relationship between hospital mortality and bloodstream infections due to Staphylococcus aureus or Pseudomonas aeruginosa. DESIGN: Prospective cohort study. SETTING: A 1,400-bed, university-affiliated urban teaching hospital. PATIENTS: Between December 2001 and September 2002, 314 patients with bacteremia due to S aureus or P aeruginosa were prospectively evaluated. INTERVENTION: Prospective patient surveillance and data collection. RESULTS: Thirteen patients (4.1%) received inadequate initial antibiotic treatment. Fifty-four patients (17.2%) died during hospitalization. Hospital mortality was statistically greater for patients with bloodstream infections due to P aeruginosa (n = 49) compared to methicillin-sensitive S aureus (MSSA) [n = 117; 30.6% vs 16.2%, p = 0.036] and methicillin-resistant S aureus (MRSA) [n = 148; 30.6% vs 13.5%, p = 0.007]. Multiple logistic regression analysis identified the lack of response to initial medical treatment (adjusted odds ratio [AOR], 2.69; 95% confidence interval [CI], 1.83 to 3.94; p = 0.010) and endocarditis (AOR, 4.62; 95% CI, 2.45 to 8.73; p = 0.016) as independent determinants of hospital mortality. Patients with bloodstream infections due to P aeruginosa were statistically more likely to be nonresponders to early medical treatment compared to patients with MSSA (73.5% vs 11.1%, p < 0.001) and MRSA (73.5% vs 16.9%, p < 0.001) bloodstream infections. CONCLUSIONS: These data suggest that bloodstream infections due to P aeruginosa have a greater risk of hospital mortality compared to bloodstream infections due to S aureus despite adequate antibiotic treatment.     

Staphylococcus aureus bacteremia in patients with hematologic disorders.

During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit. MRSA replaced methicillin-sensitive strains (MSSA) in the last four years. The skin and upper respiratory tract were the two most common primary foci. Most episodes occurred during neutropenia. Pharyngeal colonization often preceded the development of bacteremia. Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures. Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin. The survival rate did not differ materially between MRSA and MSSA bacteremias. Secondary foci, chiefly located in the lung, were found in 30% of all patients with S. aureus bacteremia. Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients.     

Impact of the use of aminoglycosides in combination antibiotic therapy on septic shock and mortality due to Staphylococcus aureus bacteremia

BACKGROUND: The purpose of this study was to evaluate the possible impact of antimicrobial combination regimens containing an aminoglycoside (AG) on morbidity and mortality associated with S. aureus bacteremia. METHODS: All inpatients over 18 years of age with S. aureus bacteremia were prospectively enrolled in three tertiary care hospitals in France and Ireland. Patients were included in the group "treated with AG" if they received at least 24 h of aminoglycoside therapy within 7 days after a positive blood culture in combination with an effective antimicrobial against the S. aureus. A Cox's proportional hazard model was used in univariate and multivariate survival analysis, the covariate "treatment with AG" being introduced as a time-dependent covariate. RESULTS: Nine percent of the 90 patients who received AG died because of infection versus 13% in the group that did not receive a combination including an AG (p>0.05). In the multivariate Cox model, stratified by septic shock and controlling for age and Charlson-weighted index of comorbidity, the adjusted odds ratio for death due to S. aureus infection associated with the use of AG was 0.6 [95% CI: (0.2-1.9); p=0.4]. However, AG was found to have a protective effect on septic shock occurrence [OR=0.3; 95% CI: (0.1-0.7), p=0.004], controlling for age, portal of entry not related to catheter infection, and diabetes. CONCLUSION: Although there was no decrease in mortality due to S. aureus infection in patients treated with AG therapy, we found a significant benefit of AG in preventing septic shock. This data argues for the early use of AG in patients with S. aureus bacteremia.     

Epidemiology and prognosis of bacteremia: a 10-y study in a community hospital

In order to determine the epidemiology and factors influencing the outcome of adult bacteremia in a community hospital, episodes of significant bacteremia were recorded prospectively over a 10-y period (1989-98). The following variables were included: age, sex, etiology, acquisition and source of the bacteremia, risk factors, clinical manifestations, empirical antibiotic treatment and outcome. A total of 798 episodes of bacteremia were recorded (436 in males) and 185 (24%) were hospital-acquired. The most frequent source was the urinary tract, followed by the respiratory tract and primary bacteremia. The crude mortality was 14.4% (n = 111) and related mortality was 8.5% (n = 66). The most frequent etiology was Escherichia coli, followed by Streptococcus pneumoniae and Staphylococcus aureus. Multivariate analysis revealed age > 70 y, nosocomial acquisition, respiratory source, primary bacteremia, septic shock, McCabe groups I and II, leukopenia, inappropriate antibiotic treatment and etiology due to S. aureus as factors associated with crude mortality. Pseudomonas aeruginosa, Proteus spp. and Bacteroides spp. were associated with related mortality. In conclusion, it is possible to modify or eliminate factors influencing the outcome of adult bacteremia. The prevention of nosocomial infection, the use of support therapies in critical patients and appropriate antibiotic treatment are measures that can improve the prognosis of patients with bacteremia.     

Staphylococcus aureus bacteremia: compliance with standard treatment, long-term outcome and predictors of relapse

The long-term outcome of compliance with standard treatment recommendations for Staphylococcus aureus bacteremia was assessed. Cases of S. aureus bacteremia at our institution over a 2-y period were reviewed and follow-up performed by review of subsequent admissions or contact with primary care physicians. We encountered 226 cases (age 64.7 +/- 15.8 y) and most (171/226, 75.7%) had no removable source. In-hospital mortality rate was 32.7% (74/226). Follow-up of 104/152 (68.4%) survivors (for 386.7 +/- 449.8 d) revealed 23.1% (24/104) relapses: recurrent bacteremia (n = 19), distant site (n = 3) and local recurrence (n = 2). Most relapses (21124; 87.5%) occurred within 90 d of therapy. Relapse rate was higher with vancomycin treatment (20148 vs. 4/56; p < 0.001), bacteremia for > or = 3 d (9/20 vs. 15/84; p = 0.001), and failure to remove the source (6/7 vs. 6/22; p = 0.006). Vancomycin effect was independent of oxacillin susceptibility. Treatment for less than the standard 2-week duration among 19 patients with short duration of bacteremia (< 3 d) did not increase relapse rate (1/19; 5.3%). Duration of bacteremia, vancomycin therapy and failure to remove the source were predictors of relapse. Prospective studies are needed to determine if S. aureus bacteremias of short duration can be treated for 2 weeks or less, and define the optimal duration for prolonged bacteremia when vancomycin is used.     

Resistance to Extended-Spectrum Cephalosporins and Mortality in Patients with <Emphasis Type="Italic">Citrobacter freundii</Emphasis> Bacteremia

Background: This study was performed to characterize the clinical features and to identify the risk factors for resistance to extended-spectrum cephalosporins (ESCs) and for mortality in patients with Citrobacter freundii bacteremia.Patients and Methods: 105 patients (aged 15 years) with C. freundii bacteremia in 1991–2000 were retrospectively analyzed.Results: Nosocomial acquisition was identified in 78.1% of the patients. Hepatic, biliary and pancreatic disease was the most common underlying disease (65.7%) and the biliary tract was the most common site of infection (50.5%). The overall resistance rate to ESCs was 59.0% and was significantly associated with hepatic, biliary and pancreatic disease, recent surgery and procedure, biliary drainage catheter and previous antibiotic therapy in univariate analysis. However, only previous antibiotic therapy with ESCs (OR = 5.0, 95% CI 1.6–15.7, p = 0.006) and recent surgery or procedure (OR = 3.1, 95% CI 1.1–8.4, p = 0.03) were strong, independent risk factors in multivariate analysis. Mortality directly related to C. freundii bacteremia was 21.9% and there was no difference between cases with resistance and susceptibility to ESCs (19.4% vs 25.6%; p = 0.45). Mortality was significantly associated with rapidly fatal or ultimately fatal underlying disease, a solid tumor, septic shock and polymicrobial bacteremia in univariate analysis. Among patients who had therapeutic surgical procedures, mortality was lower (4.5%, p = 0.04). Multivariate analysis revealed rapidly or ultimately fatal disease, septic shock and polymicrobial bacteremia as independent prognostic factors.Conclusion: Biliary infection was the leading cause of C. freundii bacteremia. Previous antibiotic therapy, especially with ESCs, frequently predisposed for resistance to these antibiotics. However, resistance to ESCs was not associated with increased mortality. Infection 2003; 31: 202–207 DOI     

Evaluation of outcome in critically ill patients with nosocomial enterobacter bacteremia: results of a matched cohort study

STUDY OBJECTIVE: To evaluate the clinical impact of nosocomial Enterobacter bacteremia in critically ill patients. DESIGN: Retrospective (January 1992 to December 2000) matched cohort study. SETTING: Fifty-four-bed ICU (including medical, surgical, cardiosurgical ICU, and burns unit) from a university hospital. PATIENTS: Sixty-seven ICU patients with Enterobacter bacteremia (case patients) and 134 control patients. INTERVENTION: Matching of control patients (1:2 ratio) was on the basis of the APACHE (acute physiology and chronic health evaluation) II system. As expected, mortality can be derived from this severity-of-disease classification system; this matching procedure results in an equal expected mortality rate for patients with Enterobacter bacteremia and control patients. RESULTS: The overall rate of appropriate antibiotic therapy in patients with Enterobacter bacteremia was high (96%) and initiated soon after the onset of the bacteremia (0.5 +/- 0.9 days). Patients with Enterobacter bacteremia had more hemodynamic instability (p = 0.015), longer ICU stay (p < 0.001), and ventilator dependence (p < 0.001). No differences between case and control patients were found in age (52 years vs 53 years, p = 0.831), prevalence of acute renal failure (16% vs 16%, p = 0.892), and acute respiratory failure (93% vs 84%, respectively; p = 0.079). In-hospital mortality rates for case and control patients were not different (34% vs 39%, respectively; p = 0.536). CONCLUSION: After accurate adjustment for severity of underlying disease and acute illness, no difference was found between ICU patients with Enterobacter bacteremia and matched control patients. In the presence of fast and appropriate antibiotic therapy, Enterobacter bacteremia does not adversely affect the outcome in ICU patients.     

Delayed peripheral venous catheter-related Staphylococcus aureus bacteremia: onset ≥ 24 hours after catheter removal

Peripheral venous catheter (PVC)-associated bacteremia usually develops during the indwelling period. We present a review of 14 patients who developed delayed onset Staphylococcus aureus bacteremia (D-SAB), 1-6 days after PVC removal, and compare them to 29 patients with early onset PVC-related S. aureus bacteremia (E-SAB). At the time of removal, the catheter site exhibited inflammation in 8 (57.1%) cases. At SAB onset, PVC site inflammation developed in all patients. Compared to E-SAB, patients with D-SAB were more often aged ≥ 65 y (71.4% vs. 34.5%; p = 0.03) and on corticosteroids (35.7% vs. 6.9%; p = 0.02). D-SAB was more complicated with persistent (> 3 days) bacteremia (42.9% vs. 13.8%; p = 0.04), metastatic infections (35.7% vs. 6.9%; p = 0.02), and slightly higher mortality (21.4% vs. 10.3%; p = 0.3). Logistic regression revealed that the predictors of D-SAB were corticosteroids (odds ratio (OR) 2.10, 95% confidence intervals (CI) 1.16-58.61) and age ≥ 65 y (OR 1.63, 95% CI 1.12-23.30). These patients may have impaired local/systemic defenses that lead to D-SAB, or a blunted host response with delayed recognition.     

Bacteremia in a long-term care facility. Spectrum and mortality

One hundred episodes of bacteremia were studied in a primarily geriatric population. Gram-positive bacteremia accounted for 24% of all bacteremia (50% mortality rate), while gram-negative bacteremia accounted for 67% of bacteremia (25% mortality); 9% of all bacteremias were polymicrobial in nature (67% mortality). Overall mortality was 35%. The urinary tract was the most frequently identified tissue source (56%) followed by skin and subcutaneous tissue (14%) and respiratory tract (10%). Escherichia coli, Proteus species, and Klebsiella enterobacter group were the most common gram-negative organisms, Staphylococcus aureus was the most common gram-positive organism and together they accounted for approximately 75% of all bacteremia. Fifty percent of deaths occurred within 24 hours of diagnosis of bacteremia, despite appropriate antibiotic therapy. This study may help to identify risk factors for bacteremia in elderly patients.     

Risk of endocarditis among patients with prosthetic valves and Staphylococcus aureus bacteremia

PURPOSE: Staphylococcus aureus is a common cause of bacteremia and of native valve infective endocarditis. However, the risk of endocarditis in patients with a prosthetic valve who develop S. aureus bacteremia is unclear. The aim of this study was to define the risk of prosthetic valve endocarditis in patients with S. aureus bacteremia. SUBJECTS AND METHODS: All patients with a prosthetic valve or ring who developed S. aureus bacteremia during the 94-month study period were prospectively evaluated. The modified Duke criteria were used for the diagnosis of endocarditis. Patients were followed up for 12 weeks after the initial diagnosis of S. aureus bacteremia. RESULTS: The overall rate of definite prosthetic valve endocarditis among the study patients was 26/51 (51%). The risk of endocarditis was similar in patients with late (>or=12 months after valve implantation) vs. early S. aureus bacteremia (<12 months after prosthetic valve implantation) (50% vs. 52%, P=1.0), mitral vs. aortic prostheses (62% vs. 48%, P=0.24), and mechanical vs. bioprosthetic valves (62% vs. 44%, P=0.29). The 12-week mortality was higher among patients with definite vs. possible endocarditis (62% vs. 28%, P=0.019). CONCLUSION: In this investigation, approximately half of all patients with prosthetic valves who developed S. aureus bacteremia had definite endocarditis. The risk of endocarditis was independent of the type, location, or age of the prosthetic valve. The mortality of prosthetic valve endocarditis is high. All patients with a prosthetic valve who develop S. aureus bacteremia should be aggressively screened and followed for endocarditis.     

Comparison of methicillin-resistant and methicillin-sensitive Staphylococcus aureus bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) has become endemic in Detroit, accounting for 50% of bacteremias in heroin abusers. To identify the salient epidemiologic and clinical features of MRSA bacteremia, case-control studies were performed comparing 28 cases of MRSA bacteremia to 28 cases of methicillin-sensitive S. aureus (MSSA) bacteremia in intravenous drug abusers. Infective endocarditis was diagnosed in 46.4% (13 of 28). In endocarditis and nonendocarditis bacteremia alike, the duration of fever, length of hospitalization, need for surgery, and mortality rates were similar. A history of recent antimicrobial therapy, especially cephalosporins, was more common in the MRSA group (p = 0.006). Complications including neurologic, renal, vascular, and musculoskeletal manifestations were more common in the MSSA endocarditis patients than MRSA endocarditis patients, although this difference was not significant. Complications related to antibiotic therapy were similar for both groups. The case-control studies indicate that MRSA and MSSA are similar in their virulence as measured by duration of hospitalization, duration of fever, complications, and mortality.     

Predictive factors of septic shock and mortality in neutropenic patients

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January–December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001).

In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate (< 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.     

Changing pattern of bone and joint infections due to Staphylococcus aureus: study of cases of bacteremia in Denmark, 1959-1988

Of the 15,170 cases of bacteremia due to Staphylococcus aureus that occurred in Denmark between 1959 and 1988, we review 525 cases of acute hematogenous osteomyelitis and 185 cases of septic arthritis that developed subsequent to the bacteremia and 134 cases of contiguous osteomyelitis in which the bacteremia developed secondarily. The pattern of acute infections of bones and joints has changed over the three decades studied. The frequency of secondary bone or joint infections due to S. aureus bacteremia has changed, as have the phage-type pattern and antibiotic resistance of the infective strains. The prevalence of hospital-acquired cases has increased and the age distribution of patients has changed, as is reflected in an increasing number of older patients. The localization of hematogenous osteomyelitis has shifted, and the vertebral column is now the most common site of infection. The rate of chronic cases of osteomyelitis that occur following acute hematogenous osteomyelitis has been reduced from 34% to 6%. The mortality associated with S. aureus bacteremic infections of bones or joints is low compared to that associated with other cases of S. aureus bacteremia.     

Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study

Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as beta-lactam antibiotics, an assumption that remains open to debate.We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse.Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.     

Staphylococcus aureus bacteremia in diabetic patients: Endocarditis and mortality

The presentation and course of Staphylococcus aureus bacteremia in 27 diabetic patients (18 insulin-dependent) were compared with those in 34 nondiabetic patients. The groups were comparable in age, proportion with pre-existing cardiac valvular disease, community-acquired bacteremia, fever, and leukocytosis. Endocarditis (vegetation or new regurgitant murmur) was present in eight (30 percent) diabetics and four (12 percent) nondiabetics (p = 0.16). A primary focus of infection was present in 67 percent of diabetics and 65 percent of nondiabetics. Among those with a focus, six of 18 diabetics and none of 22 nondiabetics had endocarditis (p < 0.005). Fifteen of 54 (28 percent) patients who received appropriate antibiotic therapy died. After stratification for underlying illness, there was no mortality difference between those with and without endocarditis (three endocarditis deaths versus 1.78 expected), or between those with and without diabetes (four diabetic deaths versus 4.8 expected). Diabetics with staphylococcal bacteremia were more likely than nondiabetics to have endocarditis in the presence of a primary focus. They had no increase in mortality.     

Vancomycin treatment of bacteremia caused by oxacillin-resistant Staphylococcus aureus: comparison with beta-lactam antibiotic treatment of bacteremia caused by oxacillin-sensitive Staphylococcus aureus

The epidemiology and therapy of 29 episodes of bacteremia caused by oxacillin- and aminoglycoside-resistant Staphylococcus aureus (OARSA) were compared with 29 episodes of bacteremia due to oxacillin-sensitive S. aureus (OSSA) that occurred during a 36-month period. Patients with bacteremia due to OSSA were younger (P less than 0.05) and were admitted more frequently with acute traumatic injury (P less than 0.01). The overall survival rate one month after persistent bacteremia was 74% for patients with OARSA bacteremia treated with vancomycin compared with 70% for patients with OSSA bacteremia treated with a beta-lactam antibiotic. The results indicate that vancomycin is an effective antibiotic for the treatment of bacteremia caused by OARSA and suggest that its effectiveness is comparable to that of beta-lactam antibiotic treatment of bacteremia due to OSSA.