Observational Study Evaluating the Seroprotection of HepB-alum Vaccine and HepB-CpG Vaccine in People With HIV.

Background: Hepatitis B virus (HBV) vaccine seroprotection rates with conventional aluminum adjuvanted recombinant HBV vaccines, Engerix-B (HepB-alum) vaccine, among people with HIV (PWH) are varied. Heplisav-B (HepB-CpG) vaccine, a novel adjuvanted recombinant HBV vaccine, has shown higher seroprotection rates in immunocompetent patients but is not well studied in PWH. There are no published studies comparing seroprotection rates between HepB-alum and HepB-CpG in PWH. This study aims to evaluate and compare the seroprotection incidence of HepB-alum vs HepB-CpG in PWH at least 18 years of age. Methods: This retrospective, observational cohort study included adults diagnosed with HIV who received a complete series of HepB-alum or HepB-CpG at a community health center in Phoenix, Arizona. Patients had a hepatitis B surface antibody <10 IU/L at the time of the first vaccine dose. The primary outcome was a comparison of seroconversion incidence between HepB-CpG and HepB-alum. Secondary outcomes included identifying factors associated with likelihood of response to HBV vaccination. Results: A total of 120 patients were included in this study, 59 in the HepB-alum cohort and 61 in the HepB-CpG cohort. In the HepB-alum cohort, 57.6% achieved seroconversion, compared with 93.4% in the HepB-CpG cohort (P < .001). Those without diabetes were more likely to have response to a vaccine. Conclusions: Among PWH at a single community health center, HepB-CpG provided a statistically higher incidence of seroprotection against HBV compared with HepB-alum.

Advances in Diagnosis of Progressive Pulmonary and Disseminated Coccidioidomycosis.

BACKGROUND: Antibody detection is the main method for diagnosis of coccidioidomycosis, but it has limitations. The Coccidioides antigen enzyme immunoassay is recommended for testing cerebrospinal fluid in suspected meningitis. Reports on urine and serum antigen detection evaluated small numbers of patients who were mostly immunocompromised. The purpose of this study was to assess the accuracy of combined antibody and antigen detection for diagnosis. METHODS: A retrospective study, including all patients in whom Coccidioides antigen detection in serum was performed between January 2013 and May 2017, was conducted at Valleywise Health Medical Center (formerly Maricopa Integrated Health System). Sensitivity and specificity of antigen and antibody were evaluated in 158 cases and 487 controls. RESULTS: The sensitivity of antibody detection by immunodiffusion (ID) was 84.2%. The sensitivity of antigen detection was 57.0% if both urine and serum were tested and 36.7% if urine alone was tested. The sensitivity of combining antigen and ID antibody detection was 93.0%. The sensitivity of urine and serum antigen detection was 55.4% in proven and 58.7% in probable cases, 79.1% in disseminated and 41.6% in pulmonary cases, and 74.7% in immunocompromised and 40.0% in immunocompetent patients. Specificity was 99.4% for antigen detection and 96.5% for ID antibody detection. Diagnostic accuracy was 95.4% for ID antibody and antigen detection, 93.6% for ID antibody alone, and 89.1% for pathology or culture. CONCLUSIONS: These findings support combined antibody and antigen detection for diagnosis of progressive coccidioidomycosis. The diagnosis may have been missed if antigen detection was not performed.

Maternal Sepsis and Septic Shock.

The year 2015 marked the 200th anniversary of the birth of Ignaz Semmelweis, the Hungarian physician who identified unhygienic practices of physicians as a major cause of childbed fever or puerperal sepsis. Although such practices have largely disappeared as a factor in the development of chorioamnionitis and postpartum or puerperal endometritis, it is appropriate that this article on sepsis in pregnancy acknowledges his contributions to maternal health. This review describes the incidence and mortality of sepsis in pregnancy, methods to identify and define sepsis in this population, including scoring systems, causes, and sites of infection during pregnancy and parturition and management guidelines.

Role of Coccidioides Antigen Testing in the Cerebrospinal Fluid for the Diagnosis of Coccidioidal Meningitis.

BACKGROUND: Coccidioidal meningitis (CM), a common cause of chronic meningitis in endemic area, is usually diagnosed by detection of anti-Coccidioides antibodies in cerebrospinal fluid (CSF), and findings may be negative in up to one-third of cases. CSF cultures and cytology are infrequently positive. Antigen detection has been used for the diagnosis of other forms of coccidioidomycosis and meningitis caused by other mycoses. The purpose of this study was to assess the diagnostic utility of CSF Coccidioides antigen (CAg) detection for the diagnosis of CM. METHODS: The medical records of patients with clinically suspected meningitis, in whom CSF was tested for Coccidioides antibodies and CAg, were retrospectively reviewed, and CSF CAg testing was prospectively conducted in patients with CM. All specimens were submitted for CAg testing. RESULTS: Thirty-six patients with 42 episode of CM were studied. The sensitivity and specificity of CAg were 93% and 100%, respectively. Cultures of CSF were positive in 7%, antibodies were demonstrated by immunodiffusion in 67% and complement fixation in 70%, and immunoglobulin M and G antibodies were demonstrated by enzyme immunoassay in 8% and 85%, respectively. CONCLUSIONS: Testing CSF for CAg is a useful addition to diagnostic methods in suspected CM and complements testing with CSF antibodies and culture.

Invasive aspergillosis caused by Aspergillus terreus: an emerging opportunistic infection with poor outcome independent of azole therapy.

OBJECTIVES: Invasive aspergillosis (IA) caused by Aspergillus terreus is a significant cause of morbidity and mortality in patients with haematological malignancy (HM). Very few data are available in this patient population to differentiate IA patients with A. terreus from those with non-terreus species of Aspergillus to compare outcomes. We retrospectively investigated 513 HM patients who were treated for either definite or probable IA between June 1993 and August 2012 in a cancer centre. METHODS: We compared baseline characteristics, antifungal therapies and outcomes between patients infected with A. terreus (n = 96, 18.7%) and those infected with non-terreus Aspergillus species (n = 335, 65.3%). Eighty-one patients with mixed or unspecified Aspergillus infections were excluded. RESULTS: Breakthrough infections occurred more frequently in the A. terreus group (91% versus 77%, P = 0.009). A. terreus infection was associated with a lower rate of final response to antifungal therapy (21% versus 38%, P = 0.0015) and a higher rate of IA-associated mortality (51% versus 30%, P < 0.001). Multivariate analyses showed that these associations were independent of patients' clinical characteristics and the antifungal regimens they received. Factors independently associated with final response included treatment with azoles (OR 3.1, 95% CI 1.9-5.0, P < 0.0001) and Aspergillus species (A. terreus versus non-terreus Aspergillus species) (OR 0.5, 95% CI 0.3-0.98, P = 0.043). Additionally, Aspergillus species and treatment with azoles were independently associated with IA-associated mortality. CONCLUSIONS: A. terreus IA in HM patients was associated with worse outcome than IA caused by non-terreus Aspergillus species. Poor prognosis in patients with invasive A. terreus infections is independent of anti-Aspergillus azole-based treatment.

Ustilago species as a cause of central line-related blood stream infection.

Ustilago, commonly referred to as "corn smut," rarely causes human disease. Serious clinical infections caused by Ustilago species have been sparsely reported in medical literature. In this study, a case of central line infection caused by Ustilago species is presented.

Comparison of posaconazole versus weekly amphotericin B lipid complex for the prevention of invasive fungal infections in hematopoietic stem-cell transplantation.

BACKGROUND: Antifungal prophylaxis is shown to decrease the risk of invasive fungal infection (IFI) after hematopoietic stem-cell transplantation (HSCT). Posaconazole has been approved for prophylaxis in HSCT. However, it is only available orally given three times per day. We evaluated once weekly intravenous amphotericin B lipid complex (ABLC), given its broad-spectrum antifungal activity and prolonged half-life (172 hr), as an alternative prophylaxis in HSCT. METHODS: We prospectively randomized allogeneic HSCT patients to receive 7.5 mg/kg of intravenous ABLC weekly or 200 mg of posaconazole orally three times per day as prophylaxis for up to 6 weeks. Endpoints were the incidence of IFI and drug-related toxicities. ABLC was discontinued if creatinine level increased to two times the baseline or greater. RESULTS: A total of 46 patients were randomized; 40 received at least one dose of the drug and were included in the analysis: 19 received ABLC and 21 received posaconazole. All patients received tacrolimus. Apache II score, neutropenia, and creatinine, bilirubin, and alanine aminotransferase levels were similar in both groups at baseline. One patient in the ABLC arm and none in posaconazole arm developed IFI (5% vs. 0%, P=0.48). More patients in the ABLC arm doubled their serum creatinine (53% vs. 5%, P=0.001) necessitating discontinuation of the study drug. CONCLUSION: High-dose prophylactic ABLC in HSCT was associated with nephrotoxicity that could be aggravated by the concomitant use of other nephrotoxic agents. Further studies are needed to evaluate the role of weekly high-dose ABLC as antifungal prophylaxis in patients at lower risk for nephrotoxicity.

Outcome analysis of invasive aspergillosis in hematologic malignancy and hematopoietic stem cell transplant patients: the role of novel antimold azoles.

BACKGROUND: Invasive aspergillosis (IA) continues to be a leading cause of morbidity and mortality in hematologic malignancy (HM) patients. We evaluated the prognostic factors for IA in HM patients. METHODS: In this retrospective study, we included all HM patients diagnosed with proven or probable IA between June 1993 and June 2008. RESULTS: A total of 449 HM patients were analyzed, the majority of which (75%) had underlying leukemia. Multivariate logistic regression analysis showed that neutropenia for more than two weeks during IA, steroid use, and intensive care admission were independently associated with failure to respond to antifungal therapy, as well as increased IA-attributable mortality (all p-values < .01). Antifungal therapy with an antimold azole-containing regimen (voriconazole or posaconazole) was also independently associated with improved response to treatment, as well as decreased IA-attributable mortality (all p-values < .0001). Survival analysis showed that primary or salvage therapy with a regimen that contained antimold azoles was significantly associated with improved survival (p < .001). CONCLUSIONS: In HM patients, persistent neutropenia and the need for intensive care are associated with failure to respond to antifungal therapy. Use of novel antimold azoles, either as primary or salvage therapy, improves the overall outcome and IA-attributable death of HM patients with IA.

Outbreak of community-acquired methicillin-resistant Staphylococcus aureus skin infections among health care workers in a cancer center.

BACKGROUND: The incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) soft tissue infections is rising. However, CA-MRSA outbreaks among health care workers (HCWs) are rarely reported. We describe 3 clusters of CA-MRSA soft tissue infections among HCWs and the subsequent transmission to a patient. METHODS: The first cluster of boils occurred in 4 employees who worked in the ambulatory treatment clinic (area A) and 1 patient (PA1) who frequently visited area A. Three employees (EA1, EA2, and EA3) and PA1 had positive cultures. Twelve employees in 2 geographically separate diagnostic imaging areas (areas B and C) reported recent or current boils of whom EB1, EB2, EB3, and EC1 had positive cultures. Molecular subtyping using pulse-field gel electrophoresis (PFGE) was performed on all 8 isolates and confirmed by the Centers for Disease Control and Prevention laboratory. RESULTS: Relatedness of the MRSA strain was confirmed by PFGE in 7 of 8 isolates. Only EB3 was not related to the prototype CA-MRSA strain. All 7 related MRSA strains contained the typical genetic organization of staphylococcal cassette chromosome (SCC)-mec type IVa plus genes encoding Panton-Valentine Leukocidin. EB3's strain contained SCC-mec type II and was Panton-Valentine Leukocidin negative. A total of 171 questionnaires was sent. Nine of the 85 HCWs who responded reported a recent or current history of boils. Infection control conducted an education program for employees in areas A, B, and C. CONCLUSION: Early identification and control of CA-MRSA infections among HCWs is important to limit horizontal transmission to patients. Future efforts should include educational programs and guidelines for reporting and treating HCWs with MRSA infections.

Novel approach using antimicrobial catheters to improve the management of central line-associated bloodstream infections in cancer patients.

BACKGROUND: Central venous catheter (CVC) removal has often been recommended for the treatment of central line-associated bloodstream infections (CLABSIs). However, CVC removal is not always practical in patients with cancer, and changing CVCs with noncoated CVCs over guidewire may result in cross-infection of the new CVC. Therefore, the current matched retrospective cohort study was conducted to evaluate the effectiveness of exchanging infected CVCs for minocycline- and rifampin (MR)-coated CVCs in cancer patients with CLABSIs. METHODS: The authors identified all cancer patients with CLABSIs who had undergone either CVC exchange with MR-coated CVCs or CVC removal at the study institution. All patients were treated with appropriate systemic antibiotics. The exchange group was matched in a 1:2 ratio with the removal group by organism, underlying disease, and neutropenia. The demographics, clinical characteristics, and outcome were compared. Overall response was defined as the resolution of clinical signs and symptoms and eradication of bacteremia within 72 hours after CVC exchange or removal, without disease recurrence or infection-related death. RESULTS: A total of 120 cancer patients were included (40 in the exchange group and 80 in the removal group). Overall response rates were 95% in the exchange group and 76% in the removal group (P = .011). No disease recurrences or infection-related deaths occurred in the exchange group; 8 disease recurrences or deaths (11%) occurred in the removal group (P = .05). Patients in the exchange group also experienced lower rates of mechanical failure (3% vs 15%; P = .049). CONCLUSIONS: Exchanging CVCs for MR-coated CVCs in cancer patients with CLABSIs may improve the overall response rate and decrease the risk of mechanical failure, disease recurrence, and infection-related mortality.

Does combination of lipid formulation of amphotericin B and echinocandins improve outcome of invasive aspergillosis in hematological malignancy patients?

BACKGROUND: In vitro and in vivo studies suggested that combination of lipid formulation of amphotericin B (L-AMB) and echinocandins may have a synergistic or additive effect against Aspergillus. Furthermore, clinical studies suggested that this combination may improve response of invasive aspergillosis (IA). METHODS: Between August 1993 and June 2008, the authors identified a total of 159 patients with hematological malignancies who received salvage therapy for IA, with L-AMB alone, echinocandins alone, or a combination of L-AMB and echinocandins. Clinical characteristics, response to salvage therapy, and death up to 12 weeks after initiation of salvage therapy were retrospectively determined for all patients. RESULTS: Seventy patients received salvage therapy with L-AMB, 18 patients received echinocandins alone (89% of whom received caspofungin), and 71 patients received the combination therapy of amphotericin B and echinocandins (90% of who received caspofungin). The 3 salvage treatment groups were comparable in regard to clinical characteristics; graft versus host disease was more frequently encountered in the echinocandin group, whereas more patients in the L-AMB and combination groups had neutropenia and received immunotherapy. The response to salvage therapy was better in the echinocandin group (9% L-AMB, 28% echinocandins, and 21% for combination therapy). The 3 groups had a comparable rate of Aspergillus-related death (58%-64%) and overall mortality (61%-67%). CONCLUSIONS: The combination of L-AMB and echinocandins offered no advantage in terms of improving response or reducing mortality over either drug alone. Hence, this combination will only add to the cost of therapy without any improvement in outcome in patients with hematological malignancies.

Detection and control of a nosocomial respiratory syncytial virus outbreak in a stem cell transplantation unit: the role of palivizumab.

Respiratory syncytial virus (RSV) is a common community-acquired virus that causes upper and lower respiratory tract infections in children, hematologic malignancy patients, and hematopoietic stem cell transplant (HSCT) recipients. Nosocomial transmission of RSV in immunocompromised patients can significantly affect morbidity, mortality, and duration of hospitalization. Stringent infection control measurements are needed to control further hospital transmission. Prophylactic palivizumab was found to result in a significant reduction in hospitalization rates in high-risk children. In this article, we report a nosocomial outbreak of RSV in an adult HSCT unit (4 pods) from January 16 to February 4, 2004, including the infection control interventions used and the prophylactic administration of palivizumab in high-risk patients. Active surveillance identified 5 cases, a substantial increase from previous seasons (2 or 3 cases per season). All infected patients were isolated to 1 nursing pod and placed on contact isolation. All patients on the HSCT unit underwent rapid RSV antigen screening using nasal washes; this was repeated 1 week later, and 1 additional RSV case was identified. Patients identified to be at increased risk for RSV infection received prophylactic palivizumab. Routine screenings of the staff and visitors were undertaken. All patient and visitor areas were thoroughly cleaned with bleach. We educated health care workers about RSV transmission, highlighting proper hand hygiene and contact precautions. Four of 6 patients with RSV infection developed RSV pneumonia, and 2 of these patients died. Staff and visitors with upper respiratory symptoms were screened, and all were negative for RSV. Prophylactic palivizumab was administered in 16 patients who tested negative for RSV, but were considered to be at increased risk for RSV infection. None of these patients developed RSV infections. An RSV outbreak was controlled using prompt preventive measures, including cohorting patients, with a dedicated health care staff; contact isolation of patients; strict adherence to hand hygiene; and screening of visitors, family members, and health care staff for upper respiratory infection symptoms. Immunoprophylaxis with palivizumab, administered to high-risk patients, complemented strict infection control intervention. Thus, the role of palivizumab in the control of RSV hospital outbreaks merits further investigation.

Differentiating culture samples representing coagulase-negative staphylococcal bacteremia from those representing contamination by use of time-to-positivity and quantitative blood culture methods.

Differentiating true coagulase-negative staphylococcal infection from contamination has an important impact on therapeutic implications. Time to positivity reflects bacterial density and may help in the interpretation of blood cultures. We retrospectively reviewed the records of 272 patients from June 2005 to January 2008 for clinical characteristics, microbiological data, and therapeutic outcome. Four groups were identified. The first three groups, as follows, included patients with one positive quantitative blood culture: the low-colony-count group (<10 CFU/ml), the moderate-colony-count group (30 to 100 CFU/ml), and the high-colony-count group (>100 CFU/ml). The control group included patients with two positive quantitative blood cultures and definite coagulase-negative staphylococcal bloodstream infection. The high-colony-count group had shorter time to positivity (< or = 16 h) than did the low-colony-count group (P < 0.0001). The low-colony-count group had a significantly longer time to positivity, >20 h (P = 0.001), than did the moderate-colony-count group. Even though antibiotics were not provided in 71% of cases and central venous catheter was retained in 83%, the low-colony-count group had a favorable outcome, suggesting that <10 CFU/ml represents contamination. The high-colony-count group, similar to the positive control group, required antibiotics in 81% of cases and central venous catheter removal in 51% (P = 0.001). A time to positivity of < or = 16 h reflects high-grade bacteremia with CFU of >100. Similar to the positive control group, these patients required an active therapeutic approach. A time to positivity of >20 h indicates possible contamination with a CFU of <10, and active therapy may not be required.

Catheter-related Staphylococcus aureus bacteremia in cancer patients: high rate of complications with therapeutic implications.

Risk factors for complications of catheter-related Staphylococcus aureus bacteremia (CRSAB) have been studied in the general patient population but have not been well defined in cancer patients. We investigated potential risk factors for intravascular and extravascular complications in these patients. We retrospectively reviewed the records of patients with CRSAB hospitalized at our institution between January 2001 and December 2004. Demographic, clinical, laboratory, and microbiologic characteristics were extracted for the period of hospitalization and up to 3 months thereafter. Intravascular complications were defined as infective endocarditis and/or septic thrombosis. Extravascular complications included septic arthritis, deep tissue abscess, osteomyelitis, septic pulmonary emboli, septic shock, and CRSAB-related death. Ninety-one patients were included in the current study; 63% had solid tumors and the remainder had hematologic malignancies. The incidence of overall complications was 40% (n = 36); 19% (n = 17) were intravascular. On multivariate analysis, renal failure was associated with an increased risk of overall complications (odds ratio [OR], 12.78; 95% confidence interval [CI], 1.43-114.29; p = 0.0226). Patients with solid tumors were more likely to have intravascular complications (OR, 5.47; 95% CI, 1.11-27.01; p = 0.04369). Risk factors for extravascular complications included hematologic malignancy (OR, 9.56; 95% CI, 2.36-38.77; p = 0.0016) and female sex (OR, 5.25; 95% CI, 1.2-22.99; p = 0.0279). Renal failure is a risk factor for CRSAB complications in patients with cancer. Patients with solid tumors and CRSAB tend to develop intravascular complications, while patients with hematologic malignancies are prone to develop extravascular complications. Hence consideration should be given to extending the duration of therapy beyond 2 weeks.