Sequential Time to Positivity as a Prognostic Indicator in Staphylococcus aureus Bacteremia.

Background: We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods: We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results: Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10-15 hours) from the initial and 21 hours (17-29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)-infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3-5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions: The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

Post-treatment outcomes of ceftriaxone versus antistaphylococcal penicillins or cefazolin for definitive therapy of methicillin-susceptible Staphylococcus aureus bacteremia.

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with poor outcomes. Ceftriaxone offers logistical advantages over other standard therapies, though in vitro studies have questioned its efficacy and clinical studies of ceftriaxone in MSSA bacteremia are conflicting.We performed a multicenter, retrospective cohort study of adult patients who received ceftriaxone, cefazolin, or antistaphylococcal penicillins as definitive therapy for MSSA bacteremia from 2018 to 2019. Definitive therapy was defined as the antibiotic used in the outpatient setting. Patients were excluded if they received less than 7 days of outpatient therapy. Follow-up started on the date of definitive therapy completion. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic recurrence. This was analyzed with multivariable Cox regression. A total of 223 patients were included, 37 (16.6%) of whom received ceftriaxone. The most common ceftriaxone dose was 2 g daily (83.8%). The most common primary site of infection was skin/soft tissue (37.2%), unknown (21.1%), and catheter-related (15.2%). Twenty-six (11.7%) developed infective endocarditis. Median total duration of treatment was 31.0 days, and median outpatient duration was 24.0 days. Twenty-six (11.7%) developed 90-day treatment failure. After adjusting for Charlson comorbidity index, duration of therapy, and use of transesophageal echocardiography, definitive treatment with ceftriaxone was associated with treatment failure (hazard ratio 2.66, 95% confidence interval 1.15-6.12; p=0.022). Among patients with MSSA bacteremia, definitive treatment with ceftriaxone was associated with a higher risk of treatment failure within 90 days as compared to cefazolin or antistaphylococcal penicillins.

The skip phenomenon in Staphylococcus aureus bacteremia: clinical implications.

Serial blood cultures (BCs) are integral in managing Staphylococcus aureus bacteremia (SAB) to determine complication risks and treatment response. Several studies recognized the skip phenomenon (SP)- the occurrence of intermittent negative BCs and recommend obtaining additional BCs to document clearance. We examined patients with SP to determine its clinical significance. Significant differences between those who did and did not manifest the SP included higher rates of injection drug use and community-onset SAB in the SP cohort. Longer SAB duration, high-grade SAB, and complicated bacteremia were more common in the SP group. In unadjusted outcome analyses, association of SP with hospital length of stay was not significant, although a higher risk of in-hospital mortality among SP patients approached significance. Analysis of hospital survivors revealed no significant differences in 90-day relapse or 1-year mortality. Clinical implications of patients with SAB and SP indicate that serial BCs are warranted to document bacterial clearance.

Clinical Significance of Staphylococcus aureus in a Single Positive Blood Culture Bottle.

Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.

Transient Hepatitis B Surface Antigenemia Following Immunization with Heplisav-B.

OBJECTIVE: To delineate the rate and duration of transient hepatitis B surface antigenemia following Heplisav-B vaccination. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all adult patients who received Heplisav-B vaccination at our institution from January 1, 2019, through March 31, 2020, and who had hepatitis B surface antigen (HBsAg) testing within 30 days following immunization. Patients with laboratory evidence of prior hepatitis B virus infection or immunization were excluded. RESULTS: A total of 39 of 1933 patients were tested for HBsAg within 30 days after completing the Heplisav-B vaccination series; of these 39, only 6 (15.4 %) had a positive HBsAg result. Compared with the patients with negative HBsAg results, those with a positive HBsAg result had a significantly lower body mass index (24.8 kg/m2 [interquartile range (IQR), 23 to 26.4 kg/m2] vs 28.6 kg/m2 [IQR, 26.4 to 30.6 kg/m2]; P=.01) and higher prevalence of chronic kidney disease (2 of 6 [33.3%] vs 2 of 33 [6%]; P=.04). The timing of HBsAg testing after completing the vaccination series in the HBsAg-positive group was significantly earlier compared with that of the HBsAg-negative group (2 days [IQR, 0.43 to 2.25 days) vs 12 days [IQR, 10 to 15 days]; P=.0008). Active hepatitis B infection was excluded in all 6 patients. In the HBsAg-positive group, the median time from the date of Heplisav-B administration to a negative HBsAg test result was 17 days (IQR, 8 to 36 days). CONCLUSION: As with all conventional hepatitis B vaccines, transient hepatitis B surface antigenemia can be observed with Heplisav-B vaccine, particularly in those with chronic kidney disease and low body mass index.

Staphylococcus simulans bloodstream infection following CIED extraction.

A 78-year-old man with an implantable cardioverter-defibrillator (ICD) presented with chills and malaise. His history was significant for heart failure with reduced ejection fraction and complete heart block. He had undergone permanent pacemaker placement that was later upgraded to an ICD 5 years before his presentation. Physical examination revealed an open wound with surrounding erythema overlying the device site. Blood cultures obtained on admission were negative. Transesophageal echocardiogram did not show valve or lead vegetations. He underwent a prolonged extraction procedure. Postoperatively, he developed septic shock and cultures from the device, and repeat peripheral blood cultures grew Staphylococcus simulans and Staphylococcus epidermidis He was treated with intravenous vancomycin but had refractory hypotension, leading to multiorgan failure. He later expired after being transitioned to comfort care. The patient may have acquired S. simulans by feeding cows on a nearby farm, and the prolonged extraction procedure may have precipitated the bacteraemia.

Clinical Presentation, Management, and Outcomes of Patients With Brain Abscess due to Nocardia Species.

BACKGROUND: Nocardial brain abscesses are rare, and published literature describing brain abscesses due to Nocardia species is limited to individual case reports or small series. We report one of the largest contemporary retrospective studies describing risk factors, diagnostic evaluation, management, and outcomes of nocardial brain abscess. METHODS: Retrospective review of all adults with brain abscess due to culture-confirmed Nocardia species at our institution between January 1, 2009, and June 30, 2020. RESULTS: Overall, 24 patients had nocardial brain abscesses during the study period. The median age at presentation was 64 years, and 62.5% were immunocompromised. Pulmonary and cutaneous infections were the most common primary sites of nocardial infection. All 24 patients had magnetic resonance imaging performed, and the frontal lobe was the most commonly involved. The most common organism isolated was Nocardia farcinica, followed by Nocardia wallacei and Nocardia cyriacigeorgica. Thirteen patients were managed with antimicrobial therapy alone, while 11 had both medical and surgical management. In all patients, dual therapy was recommended for the initial 6 weeks of treatment, and 22 patients received at least 1 oral agent as part of their final antibiotic regimen, predominantly trimethoprim-sulfamethoxazole and linezolid. Fourteen patients achieved complete clinical and radiographic resolution of infection. CONCLUSIONS: Nocardia is an important cause of brain abscess in the immunocompromised host. Early diagnostic and therapeutic aspiration may help health care providers confirm the diagnosis, choose an appropriate antimicrobial regimen, and achieve source control.

Antistaphylococcal Penicillin vs Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Spinal Epidural Abscesses.

Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA.

Unexpected Vancomycin Pharmacokinetic Profile Secondary to Macromolecular Complexing: A Case Series.

BACKGROUND: The optimal dosing and monitoring of vancomycin has been largely debated for decades, with key guideline changes for recommended monitoring in 2009 and 2020. Current and past practices for pharmacokinetic dose optimization use serum drug assays to guide dose adjustment to effectively balance efficacy and the risks of toxicity. These assays detect both bound and unbound serum concentrations. Vancomycin is believed to be 50%-55% protein bound in most cases; however, some variability in this parameter has been previously published. The authors report 2 cases of abnormal vancomycin pharmacokinetics discovered based on unexpected serum levels during routine clinical care. METHODS: Unexpected vancomycin levels, observed during clinical care for 2 separate patients, were further evaluated to determine the source of the abnormal pharmacokinetics. In case 1, serial dilution was performed to assure that assay interference was not associated with the significant elevation (>100 mg/L). In both cases, samples were filtered using a Millipore Centrifree 30 KDa centrifugal filter to separate bound vancomycin, with a Protein G spin kit used to bind IgG and remove IgG complexes from the patient sample. In case 2, a polyethylene glycol precipitation was also performed to precipitate large-molecular-weight complexes. RESULTS: In both cases, laboratory analysis revealed abnormal vancomycin protein-binding profiles with macromolecular complex formation. Immunoglobulin G played a role in the macrocomplex in both patients. CONCLUSIONS: In cases of unusual or unexpected vancomycin pharmacokinetics in the absence of renal dysfunction, an abnormal protein-binding profile should be considered. Bound vancomycin may yield elevated serum levels, leading to poorly informed dose adjustments and risk for treatment failure. Given implications for therapeutic drug monitoring and unknown impacts on efficacy and toxicity, further investigations into population incidence and risk factors for abnormal protein binding of vancomycin are warranted.

Management and treatment of Aerococcus bacteremia and endocarditis.

OBJECTIVES: We describe our multicenter experience on diagnosis and management of Aerococcus bacteremia including the susceptibility profile of Aerococcus species and a suggested algorithm for clinicians. METHODS: Retrospective study of all patients with positive blood cultures for Aerococcus species from January 2005 to July 2020 in our institution with clinical data and susceptibility profile. Data were collected from both electronic health record and clinical microbiology laboratory database. RESULTS: There were 219 unique isolates with only the susceptibility profiles available, while 81 patients had clinical information available. Forty-nine of those cases were deemed as true bloodstream infection and the rest were of unclear clinical significance. Cases of endocarditis (n = 7) were high-grade, monomicrobial bacteremia caused by Aerococcus urinae. Patients with endocarditis were younger (66 vs 80 p < 0.05). The risk for endocarditis was higher if duration of symptoms was longer than 7 days (OR 105, 95% CI: 5-2271), or if there were septic emboli (OR 71, 95% CI: 3-1612). A DENOVA score cutoff of ≥ 3 was 100% sensitive and 89% specific in detecting endocarditis. The 30-day and 3-month all-cause mortality for bacteremia was 17% and 24%, respectively. Six out of seven patients with endocarditis survived. CONCLUSIONS: Antibiotic regimen for aerococcal bloodstream infections and endocarditis should be guided by species identification and antimicrobial susceptibility testing. DENOVA scoring system's performance in this study is more congruent to other studies. Hence, it can be used as an adjunctive tool in assessing the need for echocardiogram to rule out endocarditis. In our experience, two and four weeks of treatment for bloodstream infections and endocarditis, respectively, had good outcomes.

Mycobacterium septicum: a 6-Year Clinical Experience from a Tertiary Hospital and Reference Laboratory.

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center's experience with M. septicum from 2014 to 2020. Twelve adult patients with positive cultures for M. septicum were identified. Most cases were identified from sputum samples of individuals with underlying lung disease. Most cases involving M. septicum isolation in culture were not felt to be clinically significant. Two cases were considered possible infections, while only one case was considered a definite infection that required antimicrobial treatment. All M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. Isolates were universally resistant to clarithromycin and doxycycline. The isolation of M. septicum in culture is uncommon and requires clinical correlation to determine its clinical relevance and need for treatment. Susceptibility testing should be performed to guide therapy.