Longer Duration Of Bacteremia Research Articles

1821. Clinical Characteristics of Staphylococcus aureus Bacteremia with the Skip Phenomenon: a Case Control Study.

Abstract Background Staphylococcus aureus bacteremia (SAB) is one of the most common causes of persistent bacteremia, which is associated with complicated disease and poor clinical outcome. “The skip phenomenon (SP)” was recently proposed concept which might exhibit fluctuating blood culture positivity, but its clinical significance remained to be clarified. The aim of the study was to evaluate the clinical characteristics of SAB with the SP. Methods This is a retrospective case-control study conducted at 1141-bed university hospital during 2006-2021. Adult inpatients with more than 3 days of SAB were included. Cases were patients with SP, and controls were the rest of the patients. Duration of bacteremia was defined as bacteremic days under active antibiotic therapy counting the first day as day 1. SP was defined as at least 1 day of negative blood cultures following documented S. aureus bacteremia and preceding recurrence of a positive blood culture, which was taken within 14 days from last positive culture. Patient characteristics including medical comorbidity, implanted hardware, and focus of infection were reviewed. Results Of the 149 patients, 17 (11.4%) had the SP. A total of 20 skip phenomenon episodes among 17 cases were observed. Three patients had 2 episodes of SP. Of the 20 episodes of the SP, 7 (35.0 %) were confirmed with single set, and 13 (65.0 %) were confirmed with 2 sets of negative blood culture. The median interval from first positive blood culture to first SP episode in each case was 7 days (interquartile range [IQR], 6-16 days). Of 20 episodes of SP, 18 (90.0 %) were accompanied with fever as an indication for taking blood culture. The cases (n=17) were more likely than controls (n=132) to have a longer duration of bacteremia (median [IQR], 14 [11–36] days, vs 4 [3–7] days; p < 0.001), and diabetes mellitus (52.9 % vs 25.0 %, p=0.023). There was no significant difference in deep-seated infection (64.7 % vs 48.5 %, p=0.303), methicillin resistance rate (76.5 % vs 50.0 %, p=0.068), and 90-day mortality (17.6 % vs 27.3 %, p=0.561) between cases and controls. Conclusion Our findings suggest that we should consider to take blood culture repeatedly when clinically indicated, even if we confirmed the negativity once before. Disclosures All Authors: No reported disclosures.

Comparison of Sequential Dalbavancin With Standard-of-Care Treatment for Staphylococcus aureus Bloodstream Infections.

BackgroundDalbavancin (DAL) is a long-acting lipoglycopeptide with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). This study investigates DAL as sequential therapy in S. aureus bloodstream infections (BSIs).MethodsWe conducted a retrospective cohort study from 2014 to 2021 comparing sequential DAL with standard-of-care therapy (SoC) for S. aureus BSI. The primary outcome was 90-day clinical failure (90-day all-cause mortality or 90-day recurrence). Secondary outcomes were incidence of acute kidney injury, creatinine phosphokinase elevations, catheter-related thrombosis, and hospital-acquired infections. Analyses were adjusted using inverse probability of treatment weighting (IPTW).ResultsOverall, 225 patients (45 DAL, 180 SoC) were included. DAL patients had a higher incidence of community-acquired infection and persons who use drugs; SoC patients had more comorbidities and a longer duration of bacteremia. MRSA incidence was similar between the DAL and SoC groups. The median length of stay was 16 days among DAL recipients compared with 24 days among SoC recipients. Central catheter placement was 17.8% compared with 57.2% in the SoC group. Ninety-day clinical failure occurred in 13.3% and 18.3% of participants in the DAL and SOC groups, respectively. In IPTW-adjusted analysis, sequential DAL was not associated with 90-day clinical failure (adjusted odds ratio, 0.94; 95% CI, 0.333–2.32).ConclusionsThis study provides preliminary evidence that select patients with S. aureus BSI treated with sequential DAL have similar clinical failure rates, with significant reductions in catheter placement and hospital length of stay compared with SoC. Further prospective evaluation is needed.

Reduced Vancomycin Susceptibility, MRSA and Treatment Failure in Pediatric Staphylococcus aureus Bloodstream Infections.

Clinical implications of reduced vancomycin susceptibility (RVS) among pediatric Staphylococcus aureus bloodstream infections are unknown. We identified all children at 2 children's hospitals with ≥1 blood culture positive for S. aureus. We compared patient and clinical factors for RVS and non-RVS infections using Wilcoxon rank-sum and chi-squared tests. Treatment failure and the duration of bacteremia for RVS versus non-RVS and for methicillin-resistant Staphylococcus aureus (MRSA) versus methicillin-susceptible Staphylococcus aureus (MSSA) infections were compared using multivariable logistic and Poisson regressions, respectively. For MRSA infections, the association of empiric vancomycin monotherapy with treatment failure was assessed using multivariable logistic regression. RVS was present in 72% (309/426) of cases. No patient or infection characteristics, including methicillin resistance, were associated with RVS. RVS was associated with an increased duration of bacteremia compared with non-RVS infections, aIRR = 1.15 (95% confidence interval: 1.02-1.30). The odds of treatment failure was similar for RVS and non-RVS infections, aOR = 1.04 (0.62-1.74). In contrast, MRSA infections were more likely to have treatment failure than MSSA infections, aOR = 3.03 (95% confidence interval: 1.84-5.00). For MRSA infections, empiric vancomycin monotherapy was associated with an increased odds of treatment failure compared with non-vancomycin or combination anti-MRSA antibiotics, aOR = 3.23 (1.12-9.26). RVS was common and was associated with a longer duration of bacteremia but not with treatment failure. Treatment failure was more common for MRSA than for MSSA bloodstream infections. Empiric vancomycin monotherapy increased the odds of treatment failure for MRSA infections.

Risk Factors for Complications in Children with Staphylococcus aureus Bacteremia

To determine risk factors for complications in children with Staphylococcus aureus (S aureus) bacteremia, including methicillin resistance. Single center, retrospective cohort study of children ≤18years of age hospitalized with S aureus bacteremia. We compared clinical characteristics and outcomes between those with methicillin-sensitive S aureus (MSSA) and methicillin-resistant S aureus (MRSA) bacteremia. Multivariate regression models identified risk factors associated with developing complications and with longer duration of bacteremia. We identified 394 episodes of S aureus bacteremia, 279 (70.8%) with MSSA, and 115 (29.2%) with MRSA. Primary site of infection was catheter-related in 34%, musculoskeletal in 30%, skin/soft tissue in 10.2%, pneumonia in 6.4%, and endovascular in 6.6%. Eight children (2.0%) died within 30days because of S aureus bacteremia, 15 (3.5%) had recurrence within 30days, and 38 (9.6%) had complications including septic emboli or a metastatic focus of infection. Methicillin resistance was associated with development of a complication (aOR 3.31; 95% CI 1.60-6.85), and catheter-related infections were less likely to be associated with a complication (aOR 0.40; 95% CI 0.15-1.03). In a Poisson regression analysis on duration of bacteremia, methicillin resistance, musculoskeletal infection, endovascular infection, black race, and delayed intervention for source control were significantly associated with longer duration of bacteremia. In this cohort of children with S aureus bacteremia, MRSA infections ere associated with longer duration of bacteremia and a higher likelihood of complications.

Central line associated bloodstream infections in the NICU: Does vancomycin-intermediate heteroresistance of coagulase-negative Staphylococcus matter?

Objective: To determine whether the duration of bacteremia among patients in the NICU, as well as risk of thrombocytopenia, differed between those with a central line associated bloodstream infection (CLABSI) due to a hetero-resistant vancomycin-intermediate Staphylococcus epidermidis (hVISE) and those whose CLABSI was due to vancomycin-susceptible S. epidermidis (VSSE). Methods: This retrospective cohort study covering the period from November 2009 through April 2014 examined records for 114 patients with coagulase-negative staphylococci (CoNS) CLABSI from two tertiary-care NICUs in Québec. Results: Of 111 patients included in the final analysis, 98 had an hVISE infection. The median duration of bacteremia was 4 days (range 0–33 days) for patients with hVISE and 4 days (range 2–8 days) for patients without hVISE. The duration of bacteremia was not significantly different between those with and without hVISE infection (B=−0.56, 95% CI −2.76 to 1.65). Further, the risk of thrombocytopenia for patients with and without hVISE was not significantly different (OR 0.42, 95% CI 0.076 to 2.72). Conclusions: hVISE was not shown to be associated with a longer duration of bacteremia or a greater risk of thrombocytopenia. This suggests that hVISE may not have a greater clinical impact than VSSE in infants with CLABSI. However, due to the small number of patients with VSSE in our cohort, firm conclusions cannot be drawn. Larger, multi-centre studies are needed to assess the true clinical relevance of vancomycin-intermediate hetero-resistant coagulase-negative staphylococci (hVICoNS) and before concluding on the need for hV identification in a clinical laboratory.

Staphylococcus aureus Bacteremia in Children: The Effect of Methicillin Resistance

Background Staphylococcus aureus bacteremia can occur in children in association with skin/soft tissue, musculoskeletal, respiratory, and endovascular infections. The effect of methicillin resistance on clinical outcomes in children with S. aureus bacteremia has not been clearly described.MethodsSingle center retrospective cohort study over a 5-year period of children ≤18 years hospitalized with monomicrobial S. aureus bacteremia at a tertiary care children’s hospital. We compared baseline characteristics and clinical outcomes between those with methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia using chi-squared test for dichotomous and t-test for continuous variables. We built a multivariable linear regression model to determine the effect of methicillin resistance on duration of bacteremia.ResultsWe identified 334 episodes of S. aureus bacteremia, 233 (70%) with MSSA and 101 (30%) with MRSA. Mean age was 5.4 years; 42.6% were hospital onset infections (49.8% MSSA vs. 25.7% MRSA; P < 0.001); 68.4% (73.3% vs. 55.7%; P = 0.003) occurred in children with chronic medical conditions; and 31.5% occurred in black children (25.9% vs. 44.6%; P = 0.001). Primary site of infection was catheter-related in 31.7% (37.9% vs. 18.7%), musculoskeletal in 28.1% (25.3% vs. 34.1%); skin/soft tissue in 14.2% (13.2% vs. 16.5%); pneumonia in 6.4% (3.2% vs. 13.2%); and no source identified in 11.4% (13.7% vs. 6.6%). Eleven children (3.5%) died within 30 days of bacteremia onset (3.7% vs. 3.0%; P = 0.73), 8 (2.7%) had recurrence within 30 days (2.4% vs. 3.3%; P = 0.65), and 23.4% (18.1% vs. 35.6%; P = 0.001) developed complications including septic emboli or metastatic foci of infection. Duration of bacteremia was 2.2 days (1.8 vs. 3.0; P < 0.001). Adjusting for primary site of infection and performance of a surgical drainage procedure, methicillin resistance was associated with longer duration of bacteremia (+1.2 days; 95% CI: 0.71 to 1.66).ConclusionIn this cohort of children with S. aureus bacteremia, methicillin resistance was associated with community-onset infections, black race, increased risk for complications, and longer duration of bacteremia.Disclosures All authors: No reported disclosures.

Outcomes associated with early removal versus retention of peripherally inserted central catheters after diagnosis of catheter-associated infections in neonates

Objective: To compare clinical outcomes and hospital resource utilization of infants who had peripherally inserted central catheters removed early versus retained following diagnosis of central line-associated bloodstream infection. Study Design: In a single centre retrospective cohort study, we compared outcomes of infants who had peripherally inserted central catheters removed early versus retained after diagnosis of central line-associated bloodstream infection. Mortality, cardio-respiratory deterioration, use of blood products and antibiotics were compared between groups. Results: Over a 10-year period, of the 119 eligible infants, 38 had peripherally inserted central catheters removed early and 81 had catheters retained after diagnosis of central line-associated bloodstream infection. Baseline demographics, illness severity at onset of sepsis and distribution of organisms were similar between the groups. Infants in “catheter–retained” group required longer antibiotic usage (17 ± 9 versus 13 ± 6 days; p = 0.025) and more frequent sequential positive blood cultures [31/81 (47%) versus 8/38 (22%), p = 0.014). Infants with Gram-negative bacteremia demonstrated higher mortality when catheters were retained [43% (9/21) versus 7% (1/14); p = 0.028]. Conclusions: Retaining peripherally inserted central catheters after diagnosis of central line-associated bloodstream infection was associated with longer duration of bacteremia and prolonged exposure to systemic antibiotics as well as increased mortality in Gram-negative bacteremia.

Clinical Features and Outcomes of Cardiovascular Implantable Electronic Device Infections Due to Staphylococcal Species

Staphylococci account for the bulk of cardiovascular implantable electronic device (CIED) infections. However, a detailed analysis of clinical features and outcomes of CIED infections due to staphylococcal species has not been published. We retrospectively reviewed all cases of CIED infection seen at the Mayo Clinic from 1991 through 2008. Differences in device and host factors, clinical features, and patient outcomes were compared between cases of early and late Staphylococcus aureus and coagulase-negative staphylococci (CoNS) CIED infections. Of 280 cases of staphylococcal CIED infections, 43.9% were due to S. aureus and 56.0% were due to CoNS. Staphylococcus aureus CIED infection cases more frequently involved initially implanted devices. Late S. aureus CIED infection cases compared to late CoNS cases were associated with corticosteroid therapy, hemodialysis, implanted catheters, prosthetic valves, and remote sources of bacteremia. Cases of S. aureus endovascular infections had longer duration of bacteremia (56.0% vs 20.3% ≥3 days), longer hospitalization (37.4% vs 15.2% >20 days), and increased mortality (25.2% vs 9.5%) compared to cases of CoNS endovascular infections (p <0.001 for all comparisons). Overall, CoNS CIED infections compared to S. aureus were associated with a history of multiple device revisions and a higher number of total and abandoned leads at presentation (p <0.001 for all comparisons). In conclusion, CIED infections due to S. aureus and CoNS have distinct clinical features and outcomes.

Increased Mortality with Accessory Gene Regulator ( agr ) Dysfunction in Staphylococcus aureus among Bacteremic Patients

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 δ-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 δ-hemolysin assay examining agr function may be a simple and inexpensive approach to predicting patient outcomes and potentially optimizing antibiotic therapy.

Addition of Rifampin to Standard Therapy for Treatment of Native Valve Infective Endocarditis Caused byStaphylococcus aureus

Staphylococcus aureus is a common cause of native valve infective endocarditis (IE). Rifampin is often added to traditional therapy for the management of serious S. aureus infections. There are no large, prospective studies documenting the safety and efficacy of adjunctive therapy with rifampin for treatment of native valve S. aureus IE. We reviewed all cases of definite native valve S. aureus IE confirmed by modified Duke criteria in a large urban hospital between 1 January 2004 and 31 December 2005. A retrospective cohort analysis was used to assess the impact of the addition of rifampin to standard therapy. There were 42 cases of S. aureus IE treated with the addition of rifampin and 42 controls. Cases received a median of 20 days of rifampin (range, 14 to 48 days). Rifampin-resistant S. aureus isolates developed in nine cases who received rifampin before clearance of bacteremia (56%), while significant hepatic transaminase elevations also occurred in nine cases, all of whom had hepatitis C infection. Unrecognized significant drug-drug interactions with rifampin occurred frequently (52%). Cases were more likely to have a longer duration of bacteremia (5.2 versus 2.1 days; P < 0.001) and were less likely to survive (79% versus 95%; P = 0.048) than controls. Our results suggest that the potential for hepatotoxicity, drug-drug interactions, and the emergence of resistant S. aureus isolates warrants a careful risk-benefit assessment before adding rifampin to standard antibiotic treatment of native valve S. aureus IE until further clinical studies are performed.

Perinephric Abscess Caused by Community-Acquired Methicillin Resistant Staphylococcus aureus

To the Editors: As presented by Zaoutis et al,1 there has been a steady increase in the proportion of community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates recovered from skin and soft tissue infections in the pediatric population. Invasive infections with CA-MRSA are also on the rise, and are reportedly associated with a longer duration of bacteremia, more febrile days, and more inpatient hospital days than invasive infections with CA-MRSA.2 We report a complicated perinephric abscess caused by CA-MRSA in a toddler with a history of recent blunt abdominal trauma. A 13-month old boy was admitted to the pediatric ICU with a 3-day history of fever, vomiting, decreased activity, and abdominal distention. He was febrile to 38.3°F with a markedly tender and distended abdomen (girth 54 cm). A computed tomography scan with contrast demonstrated a subcapsular hematoma around the left kidney; thickening of the descending colon, a peri-colonic hematoma, and moderate hemoperitoneum. Ampicillin, gentamicin, and metronidazole were initiated. An exploratory laparotomy yielded 100 mL of purulent fluid from the peritoneum. A perforation measuring 5 cm in length was seen in the descending colon, and a small perforation was also noted in the Gerota fascia, actively draining purulent fluid. Six centimeters of the colon was resected at the site of perforation, and a Jackson-Pratt drain was left draining the Gerota's capsule. Antibiotics were changed to vancomycin, gentamicin, and metronidazole. Peritoneal and perinephric abscess cultures grew MRSA, which was susceptible to vancomycin, clindamycin, gentamicin, levofloxacin, linezolid, and trimethoprim-sulfamethoxazole; and resistant to ampicllin/sulbactam, cefazolin, erythromycin, oxacillin, and penicillin. He recovered after 2 weeks of parenteral therapy with vancomycin, gentamicin, and metronidazole, and 2 additional weeks of oral trimethoprim-sulfamethoxazole. The most probable mechanism for development of this abscess was blunt trauma to the abdomen resulting in renal laceration and bleeding around the kidney, followed by seeding with CA-MRSA during an episode of transient bacteremia. The delay in seeking medical care likely allowed the abscess to extend beyond the perinephric space into the peritoneum, with subsequent peritonitis and rupture of the descending colon. The CA-MRSA strain from our patient carried genes for Panton-Valentine leukocidin (PVL), a potent cytotoxin that mediates tissue necrosis and destruction of leukocytes by creating pores in leukocyte cell membranes. PVL is found in up to 72% of CA-MRSA isolates in the community,3 and may have accounted for the rapid progression of infection seen in our patient. In a recent study from Texas,4 children with osteomyelitis caused by PVL-positive isolates of CA-MRSA were more likely to have severe infection than osteomyelitis caused by CA-MRSA isolates lacking PVL genes. Zainab A. Malik, MD Nathan Litman, MD Department of Pediatrics, Division of Infectious Diseases Children's Hospital at Montefiore Bronx, NY E-mail: [email protected].

Contribution of biofilm regulatory protein A of Streptococcus mutans, to systemic virulence

Streptococcus mutans is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE), and the possibility that it could be pathogenic for those diseases has been discussed. The initial important step for the involvement of bacterial pathogens in the virulence of IE is thought to be survival in blood for an extended period. Recently, the brpA gene encoding biofilm regulatory protein A (BrpA) of S. mutans was cloned and sequenced, after which it was shown that inactivation of brpA in an isogenic mutant strain resulted in longer chain formation than in the parental strain. In the present study, a BrpA-defective isogenic mutant strain (MT8148BRD) was constructed from strain MT8148. In an analysis of its susceptibility to phagocytosis by human polymorphonuclear leukocytes (PMNs), the phagocytosis rate of MT8148BRD was shown to be significantly lower than that of MT8148 ( P < 0.01). Next, strains with various chain lengths were produced by culturing MT8148 in media with various initial pH levels, which revealed that there was a statistically negative correlation between phagocytosis susceptibility and chain length ( P < 0.01). Further, MT8148BRD was found to possess higher platelet aggregation properties than MT8148 ( P < 0.05). In addition, injection of MT8148BRD into the jugular vein of specific pathogen-free Sprague–Dawley rats resulted in a longer duration of bacteremia, which prolonged systemic inflammation for a longer period than in those infected with MT8148. These results indicate that S. mutans BrpA is associated with virulence in blood, due to its correlation to phagocytosis susceptibility and platelet aggregation properties.