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The aim of this study is to apply and evaluate the usefulness of the hybrid classifier to predict the presence of serious coronary artery disease based on clinical data and 24-hour Holter ECG monitoring. Our approach relies on an ensemble classifier applying the distributivity equation aggregating base classifiers accordingly. Such a method may be helpful for physicians in the management of patients with coronary artery disease, in particular in the face of limited access to invasive diagnostic tests, i.e., coronary angiography, or in the case of contraindications to its performance. The paper includes results of experiments performed on medical data obtained from the Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland. The data set contains clinical data, data from Holter ECG (24-hour ECG monitoring), and coronary angiography. A leave-one-out cross-validation technique is used for the performance evaluation of the classifiers on a data set using the WEKA (Waikato Environment for Knowledge Analysis) tool. We present the results of comparing our hybrid algorithm created from aggregation with the distributive equation of selected classification algorithms (multilayer perceptron network, support vector machine, k-nearest neighbors, naïve Bayes, and random forests) with themselves on raw data.

Background: Although Staphylococcus aureus is the leading cause of acute infective endocarditis (IE) in adults, Bartonella spp. has concomitantly emerged as the leading cause of "blood culture-negative IE" (BCNE). Pre-disposing factors, clinical presentation and kidney biopsy findings in Bartonella IE-associated glomerulonephritis (GN) show subtle differences and some unique features relative to other bacterial infection-related GNs. We highlight these features along with key diagnostic clues and management approach in Bartonella IE-associated GN., Methods: We conducted a pooled analysis of 89 cases of Bartonella IE-associated GN (54 published case reports and case series; 18 published conference abstracts identified using an English literature search of several commonly used literature search modalities); and four unpublished cases from our institution., Results: Bartonella henselae and Bartonella quintana are the most commonly implicated species causing IE in humans. Subacute presentation, affecting damaged native and/or prosthetic heart valves, high titer anti-neutrophil cytoplasmic antibodies (ANCA), mainly proteinase-3 (PR-3) specificity, fastidious nature and lack of positive blood cultures of these Gram-negative bacilli, a higher frequency of focal glomerular crescents compared to other bacterial infection-related GNs are some of the salient features of Bartonella IE-associated GN. C3-dominant, but frequent C1q and IgM immunofluorescence staining is seen on biopsy. A "full-house" immunofluorescence staining pattern is also described but can be seen in IE -associated GN due to other bacteria as well. Non-specific generalized symptoms, cytopenia, heart failure and other organ damage due to embolic phenomena are the highlights on clinical presentation needing a multi-disciplinary approach for management. Awareness of the updated modified Duke criteria for IE, a high index of suspicion for underlying infection despite negative microbiologic cultures, history of exposure to animals, particularly infected cats, and use of send-out serologic tests for Bartonella spp. early in the course of management can help in early diagnosis and initiation of appropriate treatment., Conclusion: Diagnosis of IE-associated GN can be challenging particularly with BCNE. The number of Bartonella IE-associated GN cases in a single institution tends to be less than IE due to gram positive cocci, however Bartonella is currently the leading cause of BCNE. We provide a much-needed discussion on this topic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kitamura, Dasgupta, Henricks, Parikh, Nadasdy, Clark, Bazan and Satoskar.)

SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in asymptomatic individuals between January 2021 and May 2022. These data were generated as part of a large university COVID monitoring program in Ohio, United States of America, and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA, and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees' saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data are consistent with COVID vaccines having achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Merling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neisseria meningitidis historically has been an infrequent and sporadic cause of urethritis and other urogenital infections. However, a nonencapsulated meningococcal clade belonging to the hyperinvasive clonal complex 11.2 lineage has recently emerged and caused clusters of urethritis cases in the United States and other countries. One of the genetic signatures of the emerging N. meningitidis urethritis clade ( Nm UC) is a chromosomal gene conversion event resulting in the acquisition of the Neisseria gonorrhoeae denitrification apparatus-the N. gonorrhoeae alleles encoding the nitrite reductase AniA, the nitric oxide (NO) reductase NorB, and the intergenic promoter region. The biological importance of the N. gonorrhoeae AniA-NorB for adaptation of the Nm UC to a new environmental niche is investigated herein. We found that oxygen consumption, nitrite utilization, and NO production were significantly altered by the conversion event, resulting in different denitrifying aerobic and microaerobic growth of the clade. Further, transcription of aniA and norB in Nm UC isolates differed from canonical N. meningitidis, and important polymorphisms within the intergenic region, which influenced aniA promoter activity of the Nm UC, were identified. The contributions of three known meningococcal regulators (NsrR, FNR, and NarQP) in controlling the denitrification pathway and endogenous NO metabolism were distinct. Overall, transcription of aniA was dampened relative to canonical N. meningitidis, and this correlated with the lower NO accumulation in the clade. Denitrification and microaerobic respiration were bolstered, and protection against host-derived NO was likely enhanced. The acquisition of the N. gonorrhoeae denitrification pathway by the Nm UC supports the clade's adaptation and survival in a microaerobic urogenital environment., Competing Interests: The authors declare no conflict of interest.

The US Neisseria meningitidis urethritis clade (US_NmUC) harbors gonococcal deoxyribonucleic acid alleles and causes gonorrhea-like urogenital tract disease. A large convenience sample of US_NmUC isolates ( N = 122) collected between January 2015 and December 2019 in Columbus, Ohio demonstrated uniform susceptibility to antibiotics recommended for gonorrhea treatment and meningococcal chemoprophylaxis., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cross-protective immunity between Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) may inform gonococcal vaccine development. Meningococcal serogroup B (MenB) outer membrane vesicle (OMV) vaccines confer modest protection against gonorrhea. However, whether urethral Nm infection protects against gonorrhea is unknown. We examined gonorrhea risk among men with US Nm urethritis clade (US_NmUC) infections., Methods: We conducted a retrospective cohort study of men with urethral US_NmUC (n = 128) between January 2015 and April 2018. Using diagnosis date as the baseline visit, we examined Ng status at return visits to compute urethral Ng risk. We compared these data to 3 referent populations: men with urethral Ng (n = 253), urethral chlamydia (Ct) (n = 251), and no urethral Ng or Ct (n = 255). We conducted sensitivity analyses to assess varied approaches to censoring, missing data, and anatomical site of infection. We also compared sequences of protein antigens in the OMV-based MenB-4C vaccine, US_NmUC, and Ng., Results: Participants were primarily Black (65%) and heterosexual (82%). Over follow-up, 91 men acquired urethral Ng. Men with urethral US_NmUC had similar Ng risk to men with prior urethral Ng (adjusted hazard ratio [aHR]: 1.27; 95% CI: .65-2.48). Men with urethral US_NmUC had nonsignificantly increased Ng risk compared with men with urethral Ct (aHR: 1.51; 95% CI: .79-2.88), and significantly increased Ng risk compared with men without urethral Ng or Ct (aHR: 3.55; 95% CI: 1.27-9.91). Most of the protein antigens analyzed shared high sequence similarity., Conclusions: Urethral US_NmUC infection did not protect against gonorrhea despite substantial sequence similarities in shared protein antigens., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Urethral infections caused by an emerging nongroupable (NG) urethrotropic clade of Neisseria meningitidis were first reported in the United States in 2015 (the "U.S. NmNG urethritis clade"). Here, we evaluate for the presence of other urethral pathogens in men with U.S. NmNG urethritis clade infection. We evaluated 129 urine specimens collected from men at a sexual health clinic, including 33 from patients with culture-confirmed or suspected urethral N. meningitidis infection and 96 specimens in which nucleic acid amplification test detected Neisseria gonorrhoeae, Chlamydia trachomatis, both pathogens, or neither pathogen. N. meningitidis was detected first by real-time PCR, followed by metagenomic shotgun sequencing of 91 specimens to identify coinfections. N. meningitidis genomes were sequenced following selective whole-genome amplification when possible. Metagenomic sequencing detected N. meningitidis in 16 of 17 specimens from culture-confirmed N. meningitidis cases, with no coinfection by other conventional urethral pathogens. Metagenomic sequencing also detected N. meningitidis in three C. trachomatis-positive specimens, one specimen positive for both N. gonorrhoeae and C. trachomatis, and nine specimens with negative N. gonorrhoeae and C. trachomatis results, eight of which had suspected Neisseria infections. N. meningitidis from culture-confirmed N. meningitidis cases belonged to the U.S. NmNG urethritis clade, while N. meningitidis identified in other specimens belonged to multiple clonal complexes. Additional urethral pathogens were predominant in non-N. meningitidis specimens, including N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, and herpes simplex virus 2. Coinfection with other conventional urethral pathogens is rare in men with culture-confirmed U.S. NmNG urethritis clade infection and points to the strong association of this clade with disease.

Background: Sexually transmitted infections (STIs) are a common reason for evaluation in the emergency department (ED). Given the overlapping risk factors for STIs, patients screened for gonorrhea and chlamydia should be tested for syphilis and HIV. Syphilis and HIV testing rates in the ED have been reported to be low. The study objective was to examine whether collaboration between emergency medicine (EM) and infectious disease (ID) providers improved syphilis and HIV testing in the ED., Methods: A multidisciplinary team of EM and ID providers was formed to identify and address barriers to syphilis and HIV testing in the ED. Syphilis, HIV, chlamydia, and gonorrhea testing and infection rates were calculated and compared during 2 time periods: preintervention (January 1, 2012-December 30, 2017) and postintervention (November 1, 2018-November 30, 2019). We also extracted clinical and laboratory data from patients with positive syphilis and HIV results during the study period., Results: The most commonly cited barrier to syphilis and HIV testing was concern about follow-up of positive results. Compared with the preintervention period, syphilis and HIV testing rates increased significantly in the postintervention period (incidence rate ratios, 30.70 [P < 0.0001] and 28.99 [P < 0.0001] for syphilis and HIV, respectively). The postintervention period was also associated with a significant increase in the identification of patients with positive syphilis and HIV results (incidence rate ratios, 7.02 [P < 0.0001] and 2.34 [P = 0.03], respectively)., Conclusions: Collaboration between EM and ID providers resulted in a significant increase in syphilis and HIV testing and diagnosis in the ED., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no relevant disclosures. This work has received The Ohio State University Wexner Medical Center Patient Care Innovation Award (principal awardee: C.M.)., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Purpose of Review: Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N. gonorrhoea (Ng), Nm can colonize urogenital and rectal mucosal surfaces and cause disease. First noted in 2015, but with origins in 2011, male urethritis clusters caused by a novel Nm clade were reported in the USA (the US&#95;NmUC). This review describes research developments that characterize this urogenital-tropic Nm., Recent Findings: The US&#95;NmUC evolved from encapsulated Nm serogroup C strains. Loss of capsule expression, lipooligosaccharide (LOS) sialylation, genetic acquisition of gonococcal alleles (including the gonococcal anaerobic growth aniA/norB cassette), antimicrobial peptide heteroresistance and high surface expression of a unique factor-H-binding protein, can contribute to the urethra-tropic phenotype. Loss-of-function mutations in mtrC are overrepresented in clade isolates. Similar to Ng, repeat US&#95;NmUC urethritis episodes can occur. The US&#95;NmUC is now circulating in the UK and Southeast Asia. Genomic sequencing has defined the clade and rapid diagnostic tests are being developed for surveillance., Summary: The US&#95;NmUC emerged as a cause of urethritis due to acquisition of gonococcal genetic determinants and phenotypic traits that facilitate urogenital tract infection. The epidemiology and pathogenesis of this urogenital-tropic pathogen continues to be defined., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide and an occasional cause of meningococcal urethritis. When isolates are unavailable for surveillance or outbreak investigations, molecular characterization of pathogens needs to be performed directly from clinical specimens, such as cerebrospinal fluid (CSF), blood, or urine. However, genome sequencing of specimens is challenging because of low bacterial and high human DNA abundances. We developed selective whole-genome amplification (SWGA), an isothermal multiple-displacement amplification-based method, to efficiently enrich, sequence, and de novo assemble N. meningitidis DNA from clinical specimens with low bacterial loads. SWGA was validated with 12 CSF specimens from invasive meningococcal disease cases and 12 urine specimens from meningococcal urethritis cases. SWGA increased the mean proportion of N. meningitidis reads by 2 to 3 orders of magnitude, enabling identification of at least 90% of the 1,605 N. meningitidis core genome loci for 50% of the specimens. The validated method was used to investigate two meningitis outbreaks recently reported in Togo and Burkina Faso. Twenty-seven specimens with low bacterial loads were processed by SWGA before sequencing, and 12 of 27 were successfully assembled to obtain the full molecular typing and vaccine antigen profile of the N. meningitidis pathogen, thus enabling thorough characterization of outbreaks. This method is particularly important for enhancing molecular surveillance in regions with low culture rates. SWGA produces enough reads for phylogenetic and allelic analysis at a low cost. More importantly, the procedure can be extended to enrich other important human bacterial pathogens.

A "reverse sequence syphilis screening" algorithm is widely used for syphilis testing. This retrospective study showed that most (65%) pregnant women with discordant screening results (treponemal multiplex flow immunoassay IgG+/rapid plasma reagin-) had a nonreactive confirmatory Treponema pallidum-particle agglutination assay, likely indicative of a false-positive reaction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Results of a study evaluating the impact of privileging pharmacists to manage microbiologic test results for patients discharged from the emergency department (ED) are reported., Methods: This was a single-center, retrospective pre-post study that was conducted at an urban academic medical center. Patients discharged from the ED with a subsequent positive microbiologic test result before and after privileging of an ED specialty practice pharmacist (ED-SPP) to manage the results independently were screened for inclusion. Time to patient notification of a required change in antimicrobial therapy was compared between groups. Numbers of erroneous interventions before and after pharmacist privileging were compared to assess the safety of implementation., Results: One hundred seventy-eight positive microbiologic test results (n = 92 pre- and n = 86 postimplementation) were included. The median time to patient notification in the pre-implementation group was 23.6 hours (range, 12.4-93 hours) and in the postimplementation group was 14.9 hours (range, 2.5-27.9 hours; P = 0.0023). As determined by the board-certified infectious disease physician, 1.1% of reviewed microbiologic test results (1 of 92) was erroneous prior to implementation of pharmacist privileging compared with 2.3% (2 of 86) after implementation (P = 0.6105)., Conclusion: Privileging ED-SPPs to assess microbiologic test results improved the time to patient notification with no statistical difference in the number of erroneous interventions between groups. These findings demonstrate the benefit of clinical privileging and provide support for expansion of this role to other ED-SPPs., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In 2015, we identified a non-groupable clade of Neisseria meningitidis that causes urethritis in men (the US&#95;NmUC). Because repeat infection is common with Neisseria gonorrhoeae, we examined whether reinfection also occurs with the US&#95;NmUC. We provide evidence that men are susceptible to repeat episodes of urethritis from the US&#95;NmUC.

Background: Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment., Objectives: To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance., Methods: Retrospective, single-center study., Results: Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups., Conclusions: In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem., (Published by Elsevier B.V.)

Aim: We sought to correlate pharmacokinetic (PK)/pharmacodynamic (PD) predictions of antibacterial efficacy and clinical outcomes in patients with augmented renal clearance (ARC) and Pseudomonas aeruginosa bacteremia or pneumonia treated with extended infusion cefepime or piperacillin/tazobactam., Materials and Methods: Cefepime (2 g every 8 h) and piperacillin/tazobactam (4.5 g every 8 h) were administered over 4 h after a loading dose infused over 30 min, and minimum inhibitory concentration was determined by E -test. Published population PK evaluations in critically ill patients were used, and PD analyses were conducted using estimated patient-specific PK parameters and known minimum inhibitory concentration values for P. aeruginosa . Concentration-time profiles were generated every 6 min using first-dose drug exposure estimates including a loading infusion, and free concentration above the minimum inhibitory concentration ( f T> MIC) was estimated. Clinical cure was defined as resolution of signs and symptoms attributable to P. aeruginosa infection without need for escalation of antimicrobial., Results: One hundred and two patients were included (36 cefepime and 66 piperacillin/tazobactam). The two groups of patients had similar age, serum creatinine, weight, and creatinine clearance. The majority of patients required intensive care unit care (63.9% vs. 63.6%) and most had pneumonia (61%). The f T>MIC (93.6 [69.9-100] vs. 57.2 [47.6-72.4], P < 0.001) and clinical cure (91.7% vs. 74.2%, P = 0.039) were significantly higher in cefepime group, whereas mortality (8.3% vs. 22.7%, P = 0.1) and infection-related mortality (0% vs. 2%, P = 0.54) were similar., Conclusions: Patients with ARC and P. aeruginosa pneumonia and/or bacteremia who received extended-infusion cefepime achieved higher f T>MIC and clinical cure than those receiving extended infusion piperacillin/tazobactam., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 International Journal of Critical Illness and Injury Science.)

Clusters of Neisseria meningitidis (Nm) urethritis among primarily heterosexual males in multiple US cities have been attributed to a unique non-encapsulated meningococcal clade (the US Nm urethritis clade, US&#95;NmUC) within the hypervirulent clonal complex 11. Resistance to antimicrobial peptides (AMPs) is a key feature of urogenital pathogenesis of the closely related species, Neisseria gonorrhoeae. The US&#95;NmUC isolates were found to be highly resistant to the model AMP, polymyxin B (PmB, MICs 64-256 µg ml -1 ). The isolates also demonstrated stable subpopulations of heteroresistant colonies that showed near total resistant to PmB (MICs 384-1024 µg ml -1 ) and colistin (MIC 256 µg ml -1 ) as well as enhanced LL-37 resistance. This is the first observation of heteroresistance in N. meningitidis. Consistent with previous findings, overall PmB resistance in US&#95;NmUC isolates was due to active Mtr efflux and LptA-mediated lipid A modification. However, whole genome sequencing, variant analyses and directed mutagenesis revealed that the heteroresistance phenotypes and very high-level AMP resistance were the result of point mutations and IS1655 element movement in the pilMNOPQ operon, encoding the type IV pilin biogenesis apparatus. Cross-resistance to other classes of antibiotics was also observed in the heteroresistant colonies. High-level resistance to AMPs may contribute to the pathogenesis of US&#95;NmUC., (© 2018 John Wiley & Sons Ltd.)

Background: The recent occurrence of congenital syphilis in Columbus, OH, raised concern for an increase in syphilis among women and infants. The objectives were to examine the rates of syphilis among men, women and infants in Ohio from 2003 to 2016 and compare these rates to the rest of the United States., Methods: This retrospective study evaluated cases of syphilis among men, women and infants from 2003 to 2016 using data from the Ohio Department of Health and the Centers for Disease Control and Prevention., Results: In Ohio from 2003 to 2016, the number of all syphilis cases among women significantly increased from 153 (2.6/100,000) to 294 (5.2/100,000), respectively (b = 0.26; P = 0.001; 95% confidence interval [CI]: 0.137-0.382). From 2003 to 2016, congenital syphilis in Ohio also increased significantly from 3 (2/100,000) to 13 cases (9.3/100,000), respectively (b = 1.05; P ≤ 0.001; 95% CI: 0.687-1.408). The increase in congenital syphilis mirrored the increase in all cases of syphilis in women but not with the rates of primary and secondary syphilis. Among men, cases of primary and secondary syphilis increased significantly in Ohio and the rest of the United States, from 156 (2.8/100,000) and 5956 (4.2/100,000) in 2003 to 622 (10.5/100,000) and 24,724 (15.6/100,000) in 2016, respectively (Ohio: b = 0.55; P < 0.001; 95% CI: 0.426-0.679; United States: b = 0.77; P < 0.001; 95% CI: 0.629-0.916)., Conclusions: The association of congenital syphilis with all syphilis cases in women highlights the importance of reporting all cases and not just primary and secondary syphilis. The increase in congenital syphilis reinforces the recommendation for repeat maternal screening during pregnancy.

Background: Increased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the "U.S. NmNG urethritis clade". Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015., Results: The earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected., Conclusions: Interspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the frequency with which it causes urethritis.

Background: Neisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae., Methods: In response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015., Results: Seventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24-38) and had a median of 2 sex partners in the last 3 months (IQR = 1-3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52)., Conclusions: Between January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Neisseria meningitidis (Nm) clonal complex 11 (cc11) lineage is a hypervirulent pathogen responsible for outbreaks of invasive meningococcal disease, including among men who have sex with men, and is increasingly associated with urogenital infections. Recently, clusters of Nm urethritis have emerged primarily among heterosexual males in the United States. We determined that nonencapsulated meningococcal isolates from an ongoing Nm urethritis outbreak among epidemiologically unrelated men in Columbus, Ohio, are linked to increased Nm urethritis cases in multiple US cities, including Atlanta and Indianapolis, and that they form a unique clade (the US Nm urethritis clade, US&#95;NmUC). The isolates belonged to the cc11 lineage 11.2/ET-15 with fine type of PorA P1.5-1, 10-8; FetA F3-6; PorB 2-2 and express a unique FHbp allele. A common molecular fingerprint of US&#95;NmUC isolates was an IS1301 element in the intergenic region separating the capsule ctr-css operons and adjacent deletion of cssA/B/C and a part of csc , encoding the serogroup C capsule polymerase. This resulted in the loss of encapsulation and intrinsic lipooligosaccharide sialylation that may promote adherence to mucosal surfaces. Furthermore, we detected an IS1301-mediated inversion of an ∼20-kb sequence near the cps locus. Surprisingly, these isolates had acquired by gene conversion the complete gonococcal denitrification nor B- ani A gene cassette, and strains grow well anaerobically. The cc11 US&#95;NmUC isolates causing urethritis clusters in the United States may have adapted to a urogenital environment by loss of capsule and gene conversion of the Neisseria gonorrheae norB - aniA cassette promoting anaerobic growth., Competing Interests: The authors declare no conflict of interest.

Prescription medication use (other than antiretroviral therapy (ART)) is highly prevalent among people living with HIV. Prescription medications may be used medically or non-medically: non-medical use includes using more medication than prescribed, using medication prescribed to someone else, or using medication for a purpose other than its prescribed use. During 12 weeks in 2014-2015, we characterized medical and non-medical prescription medication use among HIV-positive patients attending an academic medical center (n = 149) and a community clinic (n = 105). Separately for the past year and the past month, these 254 participants self-reported their use of prescription opioids, sedatives, stimulants, anti-anxiety medications, antipsychotic medications, and erectile dysfunction medications. Respondents were largely male (91%), aged 40 or older (61%), identified as gay or bisexual (79%), and were men who have sex with men (85%). ART use was nearly universal (95%). Nearly half (43%) of participants reported medical use of prescription opioids; 11% of the opioid use was reported as non-medical use. Anti-anxiety medication use was also frequent, and differed by site: 41% of community-clinic responders reported medical use of anti-anxiety medications compared to 23% of hospital clinic respondents who reported medical use. Prescription sedative use was also approximately twice as high among community-clinic participants, with medical use reported by 43% of respondents and non-medical use by 12%; in comparison, at the hospital clinic, sedative use was reported by 18% (medical) and 7% (non-medical) of participants. Stimulant use was rare in both sites. No demographic characteristic was significantly associated with medical or non-medical use of any prescription medication. The current focus of many studies on only non-medical prescription medication use not only underestimates the widespread exposure of HIV-positive individuals to these drugs, but may also underestimate potential adverse effects of prescription medications in this population.

Background: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium., Methods: Monocyte subsets (CD14 + CD16 - , CD14 + CD16 + , CD14 Dim CD16 + ) from HIV negative (HIV - ) and antiretroviral therapy-treated HIV positive (HIV + ) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration. Plasma markers of monocyte (soluble [s]CD14, sCD163) and EC (VCAM-1, ICAM-1,2, fractalkine) activation and systemic (tumor necrosis factor receptor [TNFR-I], TNFR-II) and vascular (lipoprotein-associated phospholipase A 2 [Lp-PLA 2 ]) inflammation were measured by enzyme-linked immunosorbent assay., Results: Proportions of CD16 + monocyte subsets were increased in HIV + participants. Among all monocyte subsets, levels of LFA-1 were increased and CX3CR1 levels were decreased in HIV + participants ( P < .01). Levels of sCD163, sCD14, fractalkine, ICAM-1, VCAM-1, TNFR-II, and Lp-PLA 2 were also increased in HIV + participants ( P < .05), and levels of sCD14, TNFR-I, and TNFR-II were directly related to ICAM-1 and VCAM-1 levels in HIV + participants. Expression of CX3CR1 on monocyte subsets was inversely related to plasma Lp-PLA 2 ( P < .05 for all)., Conclusions: Increased proportions of CD16 + monocytes, cells with altered adhesion molecule expression, combined with elevated levels of their ligands, may promote vascular inflammation in HIV infection., (© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Accurate and timely review of microbiological test results is a core component of antimicrobial stewardship. There is documented success of these programs in the inpatient setting; however, emergency department (ED) patients are typically not included in these initiatives. Objectives: To assess the impact of an emergency medicine pharmacist (EMP)-facilitated review process of positive microbiological test results from patients discharged from the ED as measured by time to positive result review and number of indicated interventions completed. Methods: This was a retrospective study that compared EMP-facilitated to ED charge nurse (CN)-facilitated physician review of randomly selected positive microbiological test results. Groups were compared concurrently within the time frame of July 1, 2012 through December 31, 2012. Results: One hundred seventy-eight positive microbiological test results were included (EMP, n = 91; CN, n = 87). The median (IQR) time to initial review was 3 (1.0-6.3) hours for the EMP and 2 (0.3-5.5) hours for the CN group ( p = .35). Four percent (1/25) of indicated interventions were not completed in the EMP group versus 47% (14/30) in the CN group ( p = .0004). Conclusion: An EMP was significantly less likely to miss an intervention when indicated with no difference in time to review of positive microbiological results. These findings support the role of the EMP in antimicrobial stewardship in the ED.

Neisseria meningitidis (Nm) urogenital infections, although less common than infections caused by Neisseria gonorrhoeae (Ng), have been associated with urethritis, cervicitis, proctitis, and pelvic inflammatory disease. Nm can appear similar to Ng on Gram stain analysis (gram-negative intracellular diplococci) (1-5). Because Nm colonizes the nasopharynx, men who receive oral sex (fellatio) can acquire urethral Nm infections (1,3,5). This report describes an increase in Nm-associated urethritis in men attending sexual health clinics in Columbus, Ohio, and Oakland County, Michigan.

Background: Testing women for urogenital Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) is common in sexually transmitted disease (STD) clinics. However, women may not be routinely tested for rectal GC/CT. This may lead to missed infections in women reporting anal intercourse (AI)., Methods: This was a retrospective review of all women who underwent rectal GC/CT testing from August 2012 to June 2013 at an STD clinic in Columbus, Ohio. All women who reported AI in the last year had a rectal swab collected for GC/CT nucleic acid amplification testing (n=331). Using log-binomial regression models, we computed unadjusted and adjusted associations for demographic and behavioral factors associated with rectal GC/CT infection., Results: Participants (n=331) were 47% African-American, with median age of 29 years. Prevalence of rectal GC was 6%, rectal CT was 13%, and either rectal infection was 19%. Prevalence of urogenital GC and CT was 7% and 13% respectively. Among women with rectal GC, 14% tested negative for urogenital GC. Similarly, 14% of women with rectal CT tested negative for urogenital CT. In unadjusted analyses, there was increased rectal GC prevalence among women reporting sex in the last year with an injection drug user, with a person exchanging sex for drugs or money, with anonymous partners, and while intoxicated/high on alcohol or illicit drugs. After multivariable adjustment, no significant associations persisted, but a trend of increased rectal GC prevalence was observed for women <26 years of age (p=0.06) and those reporting sex while intoxicated/high on alcohol or drugs (p=0.05). For rectal CT, only age <26 years was associated with prevalent infection in unadjusted models; this association strengthened after multivariable adjustment (prevalence ratio: 6.03; 95% confidence interval: 2.29-15.90)., Conclusion: Nearly one in five women who reported AI in the last year had rectal GC or CT infection. Urogenital testing alone would have missed 14% of rectal infections. Standardized guidelines would increase rectal GC/CT testing in women and help detect missed infections.

A 28-year-old woman who was undergoing treatment with eculizumab for paroxysmal nocturnal hemoglobinuria presented to the hospital with fevers, chills, headache, and a swollen left index finger. Blood cultures returned positive for Neisseria gonorrhoeae. We report the second case of disseminated gonococcal infection associated with the use of eculizumab.

Background: Men who have sex with men (MSM) who report receptive anal intercourse (RAI) are currently recommended to undergo at least annual screening for rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection., Methods: Using standard culture methods, we assessed the prevalence of rectal GC/CT among MSM who reported RAI in the last year (n = 326) at an urban sexually transmitted disease (STD) clinic in a midwestern US city. A subset (n = 125) also underwent rectal GC/CT screening via nucleic acid amplification testing. We examined the associations between HIV status and prevalence of rectal GC and rectal CT using unadjusted and adjusted logistic regression models., Results: The prevalence of rectal GC, rectal CT, and either rectal infection was 9%, 9%, and 15% by culture and 24%, 23%, and 38% by nucleic acid amplification testing, respectively. HIV was not associated with rectal GC prevalence in unadjusted or adjusted analyses. HIV-positive status was significantly associated with increased rectal CT prevalence in unadjusted models (odds ratio, 2.18; 95% confidence interval, 1.04-4.60); this association increased after multivariable adjustment (odds ratio, 3.14; 95% confidence interval, 1.37-7.19)., Conclusions: Men who have sex with men reporting RAI had a high prevalence of rectal GC and rectal CT. HIV-positive status was significantly associated with prevalent rectal CT but not with prevalent rectal GC.

Neisseria bacilliformis has most often been associated with infections of the oral cavity and the respiratory tract. We report a case of N. bacilliformis mitral valve endocarditis in a previously healthy adult which required valve replacement, thus confirming the opportunistic nature and pathogenic potential of this novel organism., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Bartonella spp. are a known cause of culture-negative endocarditis. We report a 42-year-old male with underlying surgically corrected congenital heart disease who was diagnosed with Bartonella henselae endocarditis involving the right-ventricle-to-pulmonary-artery conduit., (© 2012 Wiley Periodicals, Inc.)

Pregnant health care workers (HCW) may be exposed to pathogens during routine patient care duties. Although they do not seem to be at higher risk for infection compared with nonpregnant HCW, certain infections can be associated with increased maternal morbidity, mortality, and adverse perinatal outcomes. Primary prevention through vaccination is crucial. Medical providers must know which vaccines are safe during pregnancy and which should be postponed until after delivery. Pregnancy should not be a contraindication for certain postexposure prophylaxis regimens after an occupational exposure. Pregnant HCW need to be educated about specific occupational risks and the recommended infection control precautions.

This article reviews the new beta-lactam (β-lactam) antibiotics doripenem, ceftobiprole, and ceftaroline. It covers pharmacokinetic and pharmacodynamic properties, dosing, in vitro activities, safety, and clinical trial results. Doripenem (Doribax) has been approved by the US Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal and urinary tract infections. Ceftaroline has received FDA approval for the treatment of skin and soft tissue infections and community acquired pneumonia. Ceftobiprole has not received FDA approval. The article also reviews recent data suggesting increased overall mortality with Cefepime (Maxipime) use compared with other beta-lactam antibiotics and the potential risk for neurotoxicity in the setting of renal failure., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Ceftaroline fosamil is a new extended-spectrum cephalosporin with activity against drug-resistant Grampositive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. At the same time, its Gramnegative spectrum of coverage includes common respiratory pathogens such as Haemophilus influenzae and Moraxella catarrhalis, as well as wild-type Enterobacteriaceae. In vivo efficacy for the treatment of experimental endocarditis, pneumonia, myositis and osteomyelitis has been demonstrated in animal models, while efficacy in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia has been demonstrated in phase II and III clinical trials in humans. The drug is well tolerated and has a low rate of reported adverse events. The dose of ceftaroline fosamil used is 600 mg i.v. every 12 h for patients with normal renal function or mild renal dysfunction. In patients with moderate renal dysfunction, it has been suggested that ceftaroline fosamil be dosed at 400 mg i.v. over 60 min every 12 h. Ceftaroline fosamil is still under review by the U.S. FDA, and when approved, will be one of the first commercially available β-lactams with the ability to treat infections due to MRSA and other drug-resistant Gram-positive pathogens., (Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.)

Study Objective: To determine the pharmacokinetics of intravenous peramivir-an investigational neuraminidase inhibitor for the treatment of 2009 H1N1 infection or nonsubtypable influenza A thought to be the 2009 H1N1 virus-in patients concurrently receiving continuous renal replacement therapy (CRRT)., Design: Pharmacokinetic analysis., Setting: Critical care unit at a university-affiliated hospital., Patients: Two critically ill women with 2009 H1N1 influenza A treated with compassionate-use intravenous peramivir administered as a daily infusion of 600 mg over 30 minutes while receiving continuous venovenous hemodiafiltration (CVVHDF), a form of CRRT., Measurements and Main Results: Plasma samples were collected from the two patients before and 30 minutes after the fourth (first patient) and ninth (second patient) peramivir infusion to estimate minimum (C(min)) and maximum (C(max)) plasma concentrations, respectively. Two additional postinfusion concentrations were measured from each patient to estimate noncompartmental pharmacokinetic parameters of peramivir while receiving CVVHDF. In the two patients, respectively, C(min) was 2170 and 251 ng/ml, C(max) was 18,400 and 20,300 ng/ml, area under the plasma concentration-time curve from 0-24 hours (AUC(0-24)) was 178,000 and 94,400 ng·hour/ml, drug clearance was 56 and 106 ml/minutes, and plasma half-life was 7.6 and 3.7 hours. The volume of distribution adjusted for ideal body weight at steady state was 0.51 and 0.54 L/kg, respectively., Conclusion: The first patient had a slower peramivir plasma clearance compared with the second patient, but both patients had higher peramivir clearances as calculated from AUC(0-24) than those predicted by CRRT. Thus, the dosage of intravenous peramivir was appropriate in these patients. Additional pharmacokinetic data are needed to confirm these results and help guide dosing in patients receiving various forms of CRRT.

This article reviews the new beta-lactam (beta-lactam) antibiotics doripenem, ceftobiprole, and ceftaroline. It covers pharmacokinetic and pharmacodynamic properties, dosing, in vitro activities, safety, and clinical trial results. Doripenem (Doribax) has been approved by the US Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal and urinary tract infections. At this writing, ceftobiprole is under review by the FDA for approval based on results of phase 3 clinical trials, whereas at least one phase 3 clinical trial of ceftaroline has been completed. The article also reviews recent data suggesting increased overall mortality with Cefepime (Maxipime) use compared with other beta-lactam antibiotics and the potential risk for neurotoxicity in the setting of renal failure.