Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections.

The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.

Procalcitonin and Risk Prediction for Diagnosing Bacteremia in Hospitalized Patients: A Retrospective, National Observational Study.

Bacteremia is associated with significant morbidity and mortality. Timely, appropriate therapy may improve clinical outcomes, and therefore, determining which patients benefit from more comprehensive diagnostic strategies (i.e., direct specimen testing) could be of value. We performed an assessment of procalcitonin (PCT) and clinical characteristics in the discrimination of bacteremic hospitalizations. We analyzed 71,105 encounters and 14,846 visits of patients with bacteremia alongside 56,259 without an admission. The area under the receiver-operating characteristic (AUROC) curve for the prediction of bacteremia via procalcitonin was 0.782 (95% CI 0.779-0.787). The prediction modeling of clinical factors with or without PCT resulted in a similar performance to PCT alone. However, the clinically predicted risk of bacteremia stratified by PCT thresholds allowed the targeting of high-incidence bacteremia groups (e.g., ≥50% positivity). The combined use of PCT and clinical characteristics could be useful in diagnostic stewardship by targeting further advanced diagnostic testing in patients with a high predicted probability of bacteremia.

Association of sexually-transmitted infection and African-American race with Streptococcus agalactiae colonization in pregnancy.

BACKGROUND: Group B Streptococcus (GBS) remains a significant cause of neonatal infection, but the maternal risk factors for GBS colonization remain poorly defined. We hypothesized that there may be an association between antibiotic exposure during pregnancy and GBS colonization and/or the presence of inducible clindamycin resistance (iCLI-R) in GBS isolates from GBS-colonized pregnant women. METHODS: A retrospective cohort study was performed at Louisiana State University Health Sciences Center - Shreveport including demographic and clinical data from 1513 pregnant women who were screened for GBS between July 1, 2009 and December 31, 2010. RESULTS: Among 526 (34.8%) women who screened positive for GBS, 124 (23.6%) carried GBS strains with iCLI-R (GBS-iCLI-R). While antibiotic exposure, race, sexually-transmitted infection (STI) in pregnancy, GBS colonization in prior pregnancy and BMI were identified as risk factors for GBS colonization in univariate analyses, the only independent risk factors for GBS colonization were African-American race (AOR = 2.142; 95% CI = 2.092-3.861) and STI during pregnancy (AOR = 1.309; 95% CI = 1.035-1.653). Independent risk factors for GBS-iCLI-R among women colonized with GBS were non-African-American race (AOR = 2.13; 95% CI = 1.20-3.78) and younger age (AOR = 0.94; 95% CI = 0.91-0.98). Among GBS-colonized women with an STI in the current pregnancy, the only independent risk factor for iCLI-R was Chlamydia trachomatis infection (AOR = 4.31; 95% CI = 1.78-10.41). CONCLUSIONS: This study identified novel associations for GBS colonization and colonization with GBS-iCLI-R. Prospective studies will improve our understanding of the epidemiology of GBS colonization during pregnancy and the role of antibiotic exposure in alterations of the maternal microbiome.

Responding to the Challenges of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Perspectives from the Association for Molecular Pathology Infectious Disease Subdivision Leadership.

Clinical molecular laboratory professionals are at the frontline of the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing accurate, high-quality laboratory results to aid in diagnosis, treatment, and epidemiology. In this role, we have encountered numerous regulatory, reimbursement, supply-chain, logistical, and systems challenges that we have struggled to overcome to fulfill our calling to provide patient care. In this Perspective from the Association for Molecular Pathology Infectious Disease Subdivision Leadership team, we review how our members have risen to these challenges, provide recommendations for managing the current pandemic, and outline the steps we can take as a community to better prepare for future pandemics.

Alternatives to Serologic Testing for Diagnosis of Lyme Disease.

Although serologic testing remains the gold standard for laboratory diagnosis of Lyme disease, the antibody response may take several weeks to increase greater than the limit of detection. Because of this extended time frame, it is necessary to identify new diagnostic methods for earlier diagnosis and appropriate treatment of Lyme disease. Alternative diagnostic modalities, such as Borrelia culture or nucleic acid amplification testing, may be beneficial in specific clinical scenarios. In early phases of acute infection, before the development of an immune response, detection of Borrelia DNA from clinical specimens may help establish the diagnosis sooner than serologic methods.

Differential mechanisms of complement-mediated neutralization of the closely related paramyxoviruses simian virus 5 and mumps virus.

The complement system is an important component of the innate immune response to virus infection. The role of human complement pathways in the in vitro neutralization of three closely related paramyxoviruses, Simian Virus 5 (SV5), Mumps virus (MuV) and Human Parainfluenza virus type 2 (HPIV2) was investigated. Sera from ten donors showed high levels of neutralization against HPIV2 that was largely complement-independent, whereas nine of ten donor sera were found to neutralize SV5 and MuV only in the presence of active complement pathways. SV5 and MuV neutralization proceeded through the alternative pathway of the complement cascade. Electron microscopy studies and biochemical analyses showed that treatment of purified SV5 with human serum resulted in C3 deposition on virions and the formation of massive aggregates, but there was relatively little evidence of virion lysis. Treatment of MuV with human serum also resulted in C3 deposition on virions, however in contrast to SV5, MuV particles were lysed by serum complement and there was relatively little aggregation. Assays using serum depleted of complement factors showed that SV5 and MuV neutralization in vitro was absolutely dependent on complement factor C3, but was not dependent on downstream complement factors C5 or C8. Our results indicate that even though antibodies exist that recognize both SV5 and MuV, they are mostly non-neutralizing and viral inactivation in vitro occurs through the alternative pathway of complement. The implications of our work for development of paramyxovirus vectors and vaccines are discussed.

Virus growth and antibody responses following respiratory tract infection of ferrets and mice with WT and P/V mutants of the paramyxovirus Simian Virus 5.

P/V gene substitutions convert the non-cytopathic paramyxovirus Simian Virus 5 (SV5), which is a poor inducer of host cell responses in human tissue culture cells, into a mutant (P/V-CPI-) that induces high levels of apoptosis, interferon (IFN)-beta, and proinflammatory cytokines. However, the effect of SV5-P/V gene mutations on virus growth and adaptive immune responses in animals has not been determined. Here, we used two distinct animal model systems to test the hypothesis that SV5-P/V mutants which are more potent activators of innate responses in tissue culture will also elicit higher antiviral antibody responses. In mouse cells, in vitro studies identified a panel of SV5-P/V mutants that ranged in their ability to limit IFN responses. Intranasal infection of mice with these WT and P/V mutant viruses elicited equivalent anti-SV5 IgG responses at all doses tested, and viral titers recovered from the respiratory tract were indistinguishable. In primary cultures of ferret lung fibroblasts, WT rSV5 and P/V-CPI- viruses had phenotypes similar to those established in human cell lines, including differential induction of IFN secretion, IFN signaling and apoptosis. Intranasal infection of ferrets with a low dose of WT rSV5 elicited approximately 500 fold higher anti-SV5 serum IgG responses compared to the P/V-CPI- mutant, and this correlated with overall higher viral titers for the WT virus in tracheal tissues. There was a dose-dependent increase in antibody response to infection of ferrets with P/V-CPI-, but not with WT rSV5. Together our data indicate that WT rSV5 and P/V mutants can elicit distinct innate and adaptive immunity phenotypes in the ferret animal model system, but not in the mouse system. We present a model for the effect of P/V gene substitutions on SV5 growth and immune responses in vivo.