Syphilis Treatment Among People Who Are Pregnant in Six U.S. States, 2018-2021.

OBJECTIVE: To describe syphilis treatment status and prenatal care among people with syphilis during pregnancy to identify missed opportunities for preventing congenital syphilis. METHODS: Six jurisdictions that participated in SET-NET (Surveillance for Emerging Threats to Pregnant People and Infants Network) conducted enhanced surveillance among people with syphilis during pregnancy based on case investigations, medical records, and linkage of laboratory data with vital records. Unadjusted risk ratios (RRs) were used to compare demographic and clinical characteristics by syphilis stage (primary, secondary, or early latent vs late latent or unknown) and treatment status during pregnancy (adequate per the Centers for Disease Control and Prevention's "Sexually Transmitted Infections Treatment Guidelines, 2021" vs inadequate or not treated) and by prenatal care (timely: at least 30 days before pregnancy outcome; nontimely: less than 30 days before pregnancy outcome; and no prenatal care). RESULTS: As of September 15, 2023, of 1,476 people with syphilis during pregnancy, 855 (57.9%) were adequately treated and 621 (42.1%) were inadequately treated or not treated. Eighty-two percent of the cohort received timely prenatal care. Although those with nontimely or no prenatal care were more likely to receive inadequate or no treatment (RR 2.50, 95% CI, 2.17-2.88 and RR 2.73, 95% CI, 2.47-3.02, respectively), 32.1% of those with timely prenatal care were inadequately or not treated. Those with reported substance use or a history of homelessness were nearly twice as likely to receive inadequate or no treatment (RR 2.04, 95% CI, 1.82-2.28 and RR 1.83, 95% CI, 1.58-2.13, respectively). CONCLUSION: In this surveillance cohort, people without timely prenatal care had the highest risk for syphilis treatment inadequacy; however, almost a third of people who received timely prenatal care were not adequately treated. These findings underscore gaps in syphilis screening and treatment for pregnant people, especially those experiencing substance use and homelessness, and the need for systems-based interventions, such as treatment outside of traditional prenatal care settings.

Host response signature trends in persistent bacteraemia and metastatic infection due to Staphylococcus aureus and Gram-negative bacilli: a prospective multicentre observational study.

BACKGROUND: A prompt diagnosis of bacteraemia and sepsis is essential. Markers to predict the risk of persistent bacteraemia and metastatic infection are lacking. SeptiCyte RAPID is a host response assay stratifying patients according to the risk of infectious vs sterile inflammation through a scoring system (SeptiScore). In this study we explore the association between SeptiScore and persistent bacteraemia as well as metastatic and persistent infection in the context of a proven bacteraemia episode. METHODS: This is a prospective multicentre observational 14-month study on patients with proven bacteraemia caused by Staphylococcus aureus or Gram-negative bacilli. Samples for assessment by SeptiCyte were collected with paired blood cultures for 4 consecutive days after the index blood culture. RESULTS: We included 86 patients in the study, 40 with S. aureus and 46 with Gram-negative bacilli bacteraemia. SeptiScores over the follow-up were higher in patients with Gram-negative compared to S. aureus bacteraemia (median 6.4, IQR 5.5-7.4 vs 5.6 IQR 5.1-6.2, p = 0.002). Higher SeptiScores were found to be associated with positive blood cultures at follow-up (AUC = 0.86, 95%CI 0.68-1.00) and with a diagnosis of metastatic infection at day 1 and 2 of follow-up (AUC = 0.79, 95%CI 0.57-1.00 and AUC = 0.82, 95%CI 0.63-1.00 respectively) in the context of Gram-negative bacteraemia while no association between SeptiScore and the outcomes of interest was observed in S. aureus bacteraemia. Mixed models confirmed the association of SeptiScore with positive blood cultures at follow-up (p = 0.04) and metastatic infection (p = 0.03) in the context of Gram-negative bacteraemia but not S. aureus bacteraemia after adjusting for confounders. CONCLUSIONS: SeptiScores differ in the follow-up of S. aureus and Gram-negative bacteraemia. In the setting of Gram-negative bacteraemia SeptiScore demonstrated a good negative predictive value for the outcomes of interest and might help rule out the persistence of infection defined as metastatic spread, lack of source control or persistent bacteraemia.

Persistence of Detectable Pathogens by Culture-Independent Systems (T2 Magnetic Resonance) in Patients With Bloodstream Infection: Prognostic Role and Possible Clinical Implications.

BACKGROUND: Persistent Staphylococcus aureus bacteremia is associated with metastatic infection and adverse outcomes, whereas gram-negative bacteremia is normally transient and shorter course therapy is increasingly advocated for affected patients. Whether the prolonged detection of pathogen DNA in blood by culture-independent systems could have prognostic value and guide management decisions is unknown. METHODS: We performed a multicenter, prospective, observational study on 102 patients with bloodstream infection (BSI) to compare time to bloodstream clearance according to T2 magnetic resonance and blood cultures over a 4-day follow-up. We also explored the association between duration of detectable pathogens according to T2 magnetic resonance (magnetic resonance-DNAemia [MR-DNAemia]) and clinical outcomes. RESULTS: Time to bloodstream clearance according to T2 magnetic resonance was significantly longer than blood culture clearance (HR, .54; 95% CI, .39-.75) and did not differ according to the causative pathogen (P = .5). Each additional day of MR-DNAemia increased the odds of persistent infection (defined as metastatic infection or delayed source control) both in the overall population (OR, 1.98; 95% CI, 1.45-2.70) and in S. aureus (OR, 1.92; 95% CI, 1.12-3.29) and gram-negative bacteremia (OR, 2.21; 95% CI, 1.35-3.60). MR-DNAemia duration was also associated with no improvement in Sequential Organ Failure Assessment score at day 7 from infection onset (OR, 1.76; 95% CI, 1.21-2.56). CONCLUSIONS: T2 magnetic resonance may help diagnose BSI in patients on antimicrobials with negative blood cultures as well as to identify patients with metastatic infection, source control failure, or adverse short-term outcome. Future studies may inform its usefulness within the setting of antimicrobial stewardship programs.

The Congenital Syphilis Prevention Cascade: Reimagining a Missed Prevention Opportunities Framework for Effective Intervention.

ABSTRACT: Congenital syphilis (CS) rates have risen in the United States since 2013. Prevention of CS requires testing and treatment of pregnant and pregnancy-capable persons at high risk for syphilis. We developed a CS Prevention Cascade to assess how effectively testing and treatment interventions reached pregnant persons with a CS outcome.

Advantages and limitations of current diagnostic laboratory approaches in syphilis and congenital syphilis.

INTRODUCTION: The reemergence of syphilis, especially congenital syphilis, presents a significant public health threat. Accurate diagnosis of syphilis depends on recognition of a constellation of symptoms, review of medical and sexual history, and multiple laboratory tests. While reliable, current tests for syphilis can be difficult to interpret, which can lead to delays in treatment. AREA COVERED: This review summarizes the major advantages and limitations of available diagnostic laboratory methods for syphilis, provides an update on recent advances in laboratory tools, and highlights the urgent need for coordinated efforts to create new tools to halt the resurgence of syphilis. EXPERT OPINION: In syphilis, the wide variety of short-lived signs and symptoms followed by periods of latency create diagnostic challenges. Currently available laboratory tests, when positive, require additional information to interpret (prior testing, treatment, and sexual history). Point-of-care tests that can rapidly and accurately detect both treponemal and non-treponemal antibodies would be a huge step toward reducing test turnaround time and time to treatment. Incorporating biological insights and technology innovations to advance the development of direct detection assays is urgently needed. A comprehensive coordinated effort is critical to stem the tide of rising syphilis in the United States and globally.

Vital Signs: Missed Opportunities for Preventing Congenital Syphilis - United States, 2022.

Introduction: Congenital syphilis cases in the United States increased 755% during 2012-2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal and infant morbidity; these outcomes can be prevented through appropriate screening and treatment. Methods: A cascading framework was used to identify and classify missed opportunities to prevent congenital syphilis among cases reported to CDC in 2022 through the National Notifiable Diseases Surveillance System. Data on testing and treatment during pregnancy and clinical manifestations present in the newborn were used to identify missed opportunities to prevent congenital syphilis. Results: In 2022, a total of 3,761 cases of congenital syphilis in the United States were reported to CDC, including 231 (6%) stillbirths and 51 (1%) infant deaths. Lack of timely testing and adequate treatment during pregnancy contributed to 88% of cases of congenital syphilis. Testing and treatment gaps were present in the majority of cases across all races, ethnicities, and U.S. Census Bureau regions. Conclusions and implications for public health practice: Addressing missed opportunities for prevention, primarily timely testing and appropriate treatment of syphilis during pregnancy, is important for reversing congenital syphilis trends in the United States. Implementing tailored strategies addressing missed opportunities at the local and national levels could substantially reduce congenital syphilis.

Substance Use Among Persons with Syphilis During Pregnancy - Arizona and Georgia, 2018-2021.

Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined as delivery of a stillborn or live-born infant meeting the surveillance case definition for probable or confirmed congenital syphilis). The prevalence of substance use (e.g., tobacco, alcohol, cannabis, illicit use of opioids, and other illicit, nonprescription substances) in persons with a congenital syphilis pregnancy outcome (48.1%) was nearly double that among those with a noncongenital syphilis pregnancy outcome (24.6%). Persons with a congenital syphilis pregnancy outcome were six times as likely to report illicit use of opioids and four times as likely to report using other illicit, nonprescription substances during pregnancy than were persons with a noncongenital syphilis pregnancy outcome. Approximately one half of persons who used substances during pregnancy and had a congenital syphilis pregnancy outcome had late or no prenatal care. Tailored interventions should address barriers and facilitators to accessing screening and treatment for syphilis among persons who use substances. The need for syphilis screening and treatment should be addressed at any health care encounter during pregnancy, especially among persons who use substances.

Risk factors, treatment and outcomes of subacute thyroiditis secondary to COVID-19: a systematic review.

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.

The utility of paired upper and lower respiratory tract sampling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in patients with artificial airways.

Early in the coronavirus disease 2019 (COVID-19) pandemic, the CDC recommended collection of a lower respiratory tract (LRT) specimen for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing in addition to the routinely recommended upper respiratory tract (URT) testing in mechanically ventilated patients. Significant operational challenges were noted at our institution using this approach. In this report, we describe our experience with routine collection of paired URT and LRT sample testing. Our results revealed a high concordance between the 2 sources, and that all children tested for SARS-CoV-2 were appropriately diagnosed with URT testing alone. There was no added benefit to LRT testing. Based on these findings, our institutional approach was therefore adjusted to sample the URT alone for most patients, with LRT sampling reserved for patients with ongoing clinical suspicion for SARS-CoV-2 after a negative URT test.

Acute kidney injury with combination vancomycin and piperacillin-tazobactam therapy in the ICU: A retrospective cohort study.

Vancomycin and piperacillin-tazobactam are commonly used antibiotics. There is increasing evidence to indicate that these therapies in combination predispose patients to acute kidney injury (AKI). However, studies of intensive care unit (ICU) patients with these antibiotics have produced conflicting results. In this single-centre, retrospective cohort study, data was collected on ICU patients prescribed combination vancomycin and piperacillin-tazobactam (VPT) for at least 48 h, compared with patients prescribed vancomycin with either cefepime or meropenem (VMC) for the same time period. Primary outcome was incidence of AKI; secondary outcomes included a desirability of outcome ranking (DOOR) scale, and association between antibiotic duration and kidney injury. A total of 260 patients were included. AKI was observed in 27% of cases overall. Incidence of AKI was higher with VPT compared with VMC on bivariate (relative risk reduction [RRR] 1.9, 95% confidence interval [CI] 0.9-4.1, P = 0.08) and multivariate (RRR 2.2, 95% CI 1.0-4.9, P = 0.05) analyses. Longer duration of antibiotic therapy was associated with increased rates of AKI independent of which antibiotics were prescribed: RRR 4.9, 95% CI 2.1-11.1, P = <0.001 for 5-6 days compared with <5 days, and RRR 2.3, 95% CI 1.0-5.5, P = 0.05 for >7 days compared with <5 days. This study demonstrated an association between increased risk of nephrotoxicity and combination VPT therapy in ICU patients. The concept remains controversial, with recent suggestions that VPT does not truly cause nephrotoxicity. Given our findings and the weight of previous studies, there is a strong mandate to undertake prospective trials to resolve the issue.

Vaccine Safety: Myths and Misinformation.

The World Health Organization has named vaccine hesitancy as one of the top ten threats to global health in 2019. The reasons why people choose not to vaccinate are complex, but lack of confidence in vaccine safety, driven by concerns about adverse events, has been identified as one of the key factors. Healthcare workers, especially those in primary care, remain key influencers on vaccine decisions. It is important, therefore, that they be supported by having easy access to trusted, evidence-based information on vaccines. Although parents and patients have a number of concerns about vaccine safety, among the most common are fears that adjuvants like aluminum, preservatives like mercury, inactivating agents like formaldehyde, manufacturing residuals like human or animal DNA fragments, and simply the sheer number of vaccines might be overwhelming, weakening or perturbing the immune system. As a consequence, some fear that vaccines are causing autism, diabetes, developmental delays, hyperactivity, and attention-deficit disorders, amongst others. In this review we will address several of these topics and highlight the robust body of scientific evidence that refutes common concerns about vaccine safety.

Rapid testing for respiratory viruses: Impact on antibiotic use and time to patient discharge.

BACKGROUND: Influenza-like illness is often caused by respiratory viral infections, and is a frequent cause of presentation to hospital. Rapid diagnostics for respiratory viruses, with turnaround times of less than sixty minutes, are increasingly available. Early physician knowledge of positive respiratory virus tests has previously been shown to impact patient care in a paediatric population but hasn't been evaluated in adults. METHODS: Rapid testing for the respiratory viruses Influenza A, Influenza B and respiratory syncytial virus (RSV) was introduced in our institution in 2018. This reduced turnaround time for tests from more than 24 h, to 1-10 h depending on time of day. A retrospective cohort study was performed on patients presenting with influenza-like illness, in whom a nasopharyngeal swab for respiratory viruses was requested. Data was collected before and after the introduction of the rapid assay. Outcomes included antibiotic use (less or more than 24 h) and length of hospital stay (less or more than 24 h). RESULTS: In all patients who tested positive for a respiratory virus, there was an association between rapid testing and less antibiotic use. This was largely driven by paediatric cases; there was no change in prescribing for adult patients. There was no impact on timing of patient discharge. CONCLUSIONS: Rapid testing for respiratory viruses has a potentially useful role in antimicrobial stewardship. It is unclear why earlier knowledge of positive viral test didn't lead to less antibiotics in adults. This study showed no impact of rapid testing on time to patient discharge.

Outcomes of patients with a history of injecting drug use and receipt of outpatient antimicrobial therapy.

People who inject drugs (PWID) are susceptible to endovascular and deep-seated infections which require prolonged antibiotic therapy. There are concerns regarding this cohort's suitability for outpatient parenteral antimicrobial therapy (OPAT), but relatively little published data. Our aim is to publish our outcomes in this setting, to inform other clinicians' decisions regarding PWID in OPAT. We reviewed case records of all PWID in our OPAT service from July 2015 to December 2017. Successful completion of OPAT care was defined as completing the duration of parenteral therapy as planned at the outset, with expected clinical improvement. Data was collected on complications including hospital re-admission, new blood stream infections, patient non-compliance including ongoing non-prescribed intravenous drug use, and staff safety compromise. Twenty-eight of 38 (76.2%) episodes of OPAT care for PWID were completed successfully, with 724 bed days of care provided. The cohort was labour intensive to manage with high rates of re-admission, non-attendance and line-associated infections. There were no adverse events for staff safety, and no patient deaths on the programme. OPAT can be a viable option for PWID provided there is careful patient selection, good patient engagement and sufficient resources allocated for patient management.

Controlled Infection Immunization Using Delayed Death Drug Treatment Elicits Protective Immune Responses to Blood-Stage Malaria Parasites.

Naturally acquired immunity to malaria is robust and protective against all strains of the same species of Plasmodium This develops as a result of repeated natural infection, taking several years to develop. Evidence suggests that apoptosis of immune lymphocytes due to uncontrolled parasite growth contributes to the slow acquisition of immunity. To hasten and augment the development of natural immunity, we studied controlled infection immunization (CII) using low-dose exposure to different parasite species (Plasmodium chabaudi, P. yoelii, or P. falciparum) in two rodent systems (BALB/c and C57BL/6 mice) and in human volunteers, with drug therapy commencing at the time of initiation of infection. CIIs with infected erythrocytes and in conjunction with doxycycline or azithromycin, which are delayed death drugs targeting the parasite's apicoplast, allowed extended exposure to parasites at low levels. In turn, this induced strong protection against homologous challenge in all immunized mice. We show that P. chabaudi/P. yoelii infection initiated at the commencement of doxycycline therapy leads to cellular or antibody-mediated protective immune responses in mice, with a broad Th1 cytokine response providing the best correlate of protection against homologous and heterologous species of PlasmodiumP. falciparum CII with doxycycline was additionally tested in a pilot clinical study (n = 4) and was found to be well tolerated and immunogenic, with immunological studies primarily detecting increased cell-associated immune responses. Furthermore, we report that a single dose of the longer-acting drug, azithromycin, given to mice (n = 5) as a single subcutaneous treatment at the initiation of infection controlled P. yoelii infection and protected all mice against subsequent challenge.