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Background Nontyphoidal Salmonella causes an estimated 1.35 million US infections annually. Antimicrobial-resistant strains are a serious public health threat. We examined the association between resistance and the clinical outcomes of hospitalization, length-of-stay ≥3 days, and death. Methods We linked epidemiologic data from the Foodborne Diseases Active Surveillance Network with antimicrobial resistance data from the National Antimicrobial Resistance Monitoring System (NARMS) for nontyphoidal Salmonella infections from 2004 to 2018. We defined any resistance as resistance to ≥1 antimicrobial and clinical resistance as resistance to ampicillin, azithromycin, ceftriaxone, ciprofloxacin, or trimethoprim-sulfamethoxazole (for the subset of isolates tested for all 5 agents). We compared outcomes before and after adjusting for age, state, race/ethnicity, international travel, outbreak association, and isolate serotype and source. Results Twenty percent of isolates (1105/5549) had any resistance, and 16% (469/2969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs 28%, P =.01) or have length-of-stay ≥3 days (20% vs 16%, P =.01). Deaths were rare but more common among those with any than no resistance (1.0% vs 0.4%, P =.01). Outcomes for patients whose isolates had clinical resistance did not differ significantly from those with no resistance. After adjustment, any resistance (adjusted odds ratio 1.23, 95% confidence interval 1.04–1.46) remained significantly associated with hospitalization. Conclusions We observed a significant association between nontyphoidal Salmonella infections caused by resistant pathogens and likelihood of hospitalization. Clinical resistance was not associated with poorer outcomes, suggesting that factors other than treatment failure (eg, strain virulence, strain source, host factors) may be important. [ABSTRACT FROM AUTHOR]

The article presents a study which examined azithromycin prescriptions in children from birth to 19 years of age. Topics discussed include data collected in the study, a high prevalence of penicillin (PCN) allergy in the cohort of patients who were prescribed azithromycin, and age distribution of children who received azithromycin prescriptions during the study period.

Aim: Campylobacter is the leading bacterial pathogen that causes foodborne illnesses worldwide. Pasture farming is regarded as an important source of agricultural production for small farming communities. Consumer preference for pasture-raised animal products has increased; however, there is a paucity of information on the microbiological quality of pasture-raised poultry products. The purpose of this study was to explore genetic relatedness of thermophilic Campylobacter isolates, to assess antibiotic resistance phenotypically and genotypically, and to screen the presence of virulence determinants of Campylobacter isolates from pasture-raised poultry farms from southeastern United States. Methods: Ninety-seven Campylobacter isolates previously identified by Q7 BAX® System Real-Time PCR were genotyped by multilocus sequence typing (MLST). Campylobacter isolates were then evaluated for their phenotypic antimicrobial susceptibility against nine antimicrobial agents using Sensititre plates. Additionally, Campylobacter isolates were tested for the presence of antimicrobial resistance-associated elements. Furthermore, Campylobacter isolates were screened for the presence of 13 genes encoding putative virulence factors by PCR. These included genes involved in motility (flaA and flhA), adhesion and colonization (cadF, docC, racR, and virB11), toxin production (cdtA, cdtB, cdtC, wlaN, and ceuE) and invasion (ciaB and iamA). Results: Among 97 Campylobacter isolates, Campylobacter jejuni (n  =  79) and Campylobacter coli (n  =  18) were identified. By MLST, C. jejuni isolates were assigned to seven clonal complexes. Among them, ST-353, ST-607 and ST-21 were the most common STs recognized. All C. coli (n  =  18) isolates were included in CC-828. Interestingly, eight STs identified were not belonging any previous identified clonal complex. Campylobacter isolates displayed a high resistance rate against tetracycline (81.4%), while a low rate of resistance was observed against macrolides (azithromycin and erythromycin), quinolones and fluoroquinolones (nalidixic acid and ciprofloxacin), aminoglycosides (gentamicin), ketolide (telithromycin), amphenicol (florfenicol) and lincomycin (clindamycin). Thirteen isolates (13.54%) were pan-susceptible to all tested antibiotics, while nine isolates were multi-antimicrobial resistant (MAR; resist to three or more antimicrobial classes). Interestingly, there were no isolates resistant to all antimicrobial classes. Thr86Ile mutation was identified in all quinolones resistant strains. Erythromycin encoding gene (ermB) was identified in 75% of erythromycin resistant isolates. The A2075 mutation was detected in one erythromycin resistant strain, while A2074 could not be identified. The tetO gene was identified in 93.7% of tetracycline resistant isolates and six tetracycline susceptible isolates. In conclusion, the results of this study revealed that Campylobacter isolates from pasture-raised poultry farms showed the ST relatedness to Campylobacter isolates commonly associated with humans, indicating pasture-raised broiler flocks, similar to conventionally-reared broiler flocks, as a potential vector for antibiotic-resistant and pathogenic strains of thermophilic Campylobacter to humans. [ABSTRACT FROM AUTHOR]

Background: The early surge of the novel coronavirus disease 2019 (COVID-19) pandemic introduced a significant clinical challenge due to the high case-fatality rate in absence of evidence-based recommendations. The empirical treatment modalities were relegated to historical expertise from the traditional management of acute respiratory distress syndrome (ARDS) in conjunction with off-label pharmaceutical agents endorsed under the "emergency use authorization" (EUA) paradigm by regulatory agencies. This study was designed to evaluate the insights from the "fail-and-learn" strategy in 2020 before the availability of COVID-19 vaccines and access to reliable insights from high-quality randomized controlled trials. Methods: A retrospective, multicenter, propensity-matched, case-control study was performed on a data registry comprising 186 hospitals from a national health care system in the United States, designed to investigate the efficacy of empirical treatment modalities during the early surge of the COVID-19 pandemic in 2020. Reflective of the time-windows of the initial two surges of the pandemic in 2020, patients were stratified into "Early 2020" (March 1–June 30) versus "Late 2020" (July 1–December 31) study cohorts. Logistic regression was applied to determine the efficacy of prevalent medications (remdesivir, azithromycin, hydroxychloroquine, corticosteroids, tocilizumab) and supplemental oxygen delivery modalities (invasive vs. non-invasive ventilation) on patient outcomes. The primary outcome measure was in-hospital mortality. Group comparisons were adjusted for covariates related to age, gender, ethnicity, body weight, comorbidities, and treatment modalities pertinent to organ failure replacement. Results: From a total of 87,788 patients in the multicenter data registry screened in this study, 9,638 patients were included who received 19,763 COVID-19 medications during the first two waves of the 2020 pandemic. The results showed a minimal, yet statistically significant, association with hydroxychloroquine in "Early 2020" and remdesivir in "Late 2020" with reduced odds of mortality (odds ratios 0.72 and 0.76, respectively; P = 0.01). Azithromycin was the only medication associated with decreased odds of mortality during both study time-windows (odds ratios 0.79 and 0.68, respectively; P < 0.01). In contrast, the necessity for oxygen supply showed significantly increased odds of mortality beyond the effect of all investigated medications. Of all the covariates associated with increased mortality, invasive mechanical ventilation had the highest odds ratios of 8.34 in the first surge and 9.46 in in the second surge of the pandemic (P < 0.01). Conclusion: This retrospective multicenter observational cohort study on 9,638 hospitalized patients with severe COVID-19 during revealed that the necessity for invasive ventilation had the highest odds of mortality, beyond the variable effects observed by administration of the prevalent EUA-approved investigational drugs during the first two surges of the early 2020 pandemic in the United States. [ABSTRACT FROM AUTHOR]

The article discusses research which evaluated trends in antibiotic dispensations and treatment of acute sinusitis between 2003 to 2020 using the MarketScan Commercial Claims and Encounters Database. The study assessed the impact of the Infectious Diseases society of America's guidelines on antibiotic selection and prescribing practices. Results revealed changes in the proportion of children dispensed with amoxicillin, azithromycin, cefdinir and amoxicillin-clavulanate.

The emergence of antimicrobial resistance (AMR) in commensal and pathogenic enteric bacteria of swine is a public health threat. This study evaluated publicly available AMR surveillance data collected by the National Antimicrobial Resistance Monitoring System (NARMS) by assessing AMR patterns and temporal trends in commensal E. coli isolated from cecal samples of swine at slaughter across the United States. We applied the Mann-Kendall test (MKT) and a linear regression trend line to detect significant trends in the proportion of resistant isolates to individual antimicrobials over the study period. A Poisson regression model assessed differences among years in the number of antimicrobials to which an E. coli isolate was resistant. Among the 3237 E. coli isolates, a very high prevalence of resistance for tetracycline (67.62%), and high resistance for streptomycin (24.13%), and ampicillin (21.10%) were identified. The MKT and the linear trend line showed a significantly increasing temporal trend for amoxicillin-clavulanic acid, ampicillin, azithromycin, cefoxitin, ceftriaxone, and trimethoprim-sulfamethoxazole. Compared to 2013 the number of antimicrobials to which an E. coli isolate was resistant was significantly higher in the years 2017, 2018, and 2019. The increasing temporal trend of resistance to important antimicrobials for human medicine (e.g., third-generation cephalosporins) and the increase in multidrug resistance in the later years of the study are concerning and should be followed up by studies to identify sources and risk factors for the selection of AMR. [ABSTRACT FROM AUTHOR]

Background: Extensively drug-resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) poses a grave threat to public health due to increased mortality and morbidity caused by typhoid fever. Honey is a promising antibacterial agent, and we aimed to determine the antibacterial activity of honey against XDR S. Typhi. Methods: We isolated 20 clinical isolates of XDR S. Typhi from pediatric septicemic patients and determined the minimum inhibitory concentrations (MICs) of different antibiotics against the pathogens using the VITEK 2 Compact system. Antimicrobial-resistant genes carried by the isolates were identified using PCR. The antibacterial efficacy of five Pakistani honeys was examined using agar well diffusion assay, and their MICs and minimum bactericidal concentrations (MBCs) were determined with the broth microdilution method. Results: All 20 isolates were confirmed as S. Typhi. The antibiogram phenotype was confirmed as XDR S. Typhi with resistance to ampicillin (≥ 32 µg/mL), ciprofloxacin (≥ 4 µg/mL), and ceftriaxone (≥ 4 µg/mL) and sensitivity to azithromycin (≤ 16 µg/mL) and carbapenems (≤ 1 µg/mL). Molecular conformation revealed the presence of blaTM-1, Sul1, qnrS, gyrA, gyrB, and blaCTX-M-15 genes in all isolates. Among the five honeys, beri honey had the highest zone of inhibition of 7–15 mm and neem honey had a zone of inhibition of 7–12 mm. The MIC and MBC of beri honey against 3/20 (15%) XDR S. Typhi isolates were 3.125 and 6.25%, respectively, while the MIC and MBC of neem were 3.125 and 6.25%, respectively, against 3/20 (15%) isolates and 6.25 and 12.5%, respectively, against 7/20 (35%) isolates. Conclusion: Indigenous honeys have an effective role in combating XDR S. Typhi. They are potential candidates for clinical trials as alternative therapeutic options against XDR S. Typhi isolates. [ABSTRACT FROM AUTHOR]

Reports of Salmonella enterica I serotype 4, [5],12:i:-infections resistant to ampicillin, streptomycin, sulphamethoxazole, and tetracycline (ASSuT) have been increasing. We analyzed data from 5 national surveillance systems to describe the epidemiology, resistance traits, and genetics of infections with this Salmonella strain in the United States. We found ASSuT-resistant Salmonella 4, [5],12:i:-increased from 1.1% of Salmonella infections during 2009-2013 to 2.6% during 2014-2018; the proportion of Salmonella 4, [5],12:i:-isolates without this resistance pattern declined from 3.1% to 2.4% during the same timeframe. Among isolates sequenced during 2015-2018, a total of 69% were in the same phylogenetic clade. Within that clade, 77% of isolates had genetic determinants of ASSuT resistance, and 16% had genetic determinants of decreased susceptibility to ciprofloxacin, ceftriaxone, or azithromycin. Among outbreaks related to the multidrug-resistant clade, 63% were associated with pork consumption or contact with swine. Preventing Salmonella 4, [5],12:i:-carriage in swine would likely prevent human infections with this strain. [ABSTRACT FROM AUTHOR]

Antibiotics are not routinely recommended for patients with Campylobacter enterocolitis. We conducted a retrospective review of hospitalized patients younger than 18 years diagnosed with Campylobacter enterocolitis from July 2015 to December 2019. This study aimed to investigate antibiotic prescribing practices and the clinical outcomes and to evaluate the factors associated with antibiotic use. A total of 157 patients (median age, 10.7 years) were included in this study. Most patients (93.0%) had a fever, and a quarter of the patients complained of bloody diarrhea. The overall antibiotic prescribing rate was 36.7% (57/157), 91.2% of the patients received antibiotics within hospital day 2. The semi-annual antibiotic prescribing rate ranged from 16.7 to 50.0%. There were no increasing or decreasing trends in antibiotic prescribing rates. Cephalosporins were the most prescribed antibiotics for initial antibiotic therapy. Azithromycin use increased significantly during the study period. The independent factors associated with early antibiotic therapy were leukocytosis (adjusted odds ratio (aOR), 3.95; 95% confidence interval (CI), 1.76–9.27), C-reactive protein ≥50 mg/L (aOR, 4.19; 95% CI, 1.84–10.21), and performing abdominal imaging studies (aOR, 3.44; 95% CI, 1.55–7.99). There was no significance in defervescence between the early and no-antibiotic therapy groups (p = 0.232). A careful assessment of the need for antibiotic therapy in patients with acute diarrhea should be conducted to avoid unnecessary use. After identifying the causative pathogens, the appropriateness of antibiotic prescription should be evaluated. [ABSTRACT FROM AUTHOR]

The article reports that Chlamydia trachomatis is the most common bacterial sexually transmitted infection in the United States with several million cases reported in 2021. Topics include considered two-thirds of annual cases are among adolescents and young adults and examines untreated Chlamydia infections lead to serious reproductive health morbidity including pelvic inflammatory disease, ectopic pregnancy and infertility.

Background We aimed to describe trends in adverse outcomes among patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between February and September 2020 within a national healthcare system. Methods We identified enrollees in the national United States Veterans Affairs healthcare system who tested positive for SARS-CoV-2 between 28 February 2020 and 30 September 2020 (n = 55 952), with follow-up extending to 19 November 2020. We determined trends over time in incidence of the following outcomes that occurred within 30 days of testing positive: hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death. Results Between February and July 2020, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), which subsequently plateaued between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, documented symptoms, and laboratory tests, including among subgroups of patients hospitalized, admitted to the ICU, or treated with mechanical ventilation. From February to September, there were decreases in the use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%), vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) and increases in the use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%), and remdesivir (1.7% to 45.4%) among hospitalized patients. Conclusions The risk of adverse outcomes in SARS-CoV-2–positive patients decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics and may reflect changing treatment practices or viral pathogenicity. [ABSTRACT FROM AUTHOR]

Background Trends in prescribing for nursing home (NH) residents, which may have been influenced by the coronavirus disease 2019 (COVID-19) pandemic, have not been characterized. Methods Long-term care pharmacy data from 1944 US NHs were used to evaluate trends in prescribing of antibiotics and drugs that were investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased NH occupancy during the pandemic, monthly prevalence of residents with a prescription dispensed per 1000 residents serviced was calculated from January to October and compared as relative percent change from 2019 to 2020. Results In April 2020, prescribing was significantly higher in NHs for drugs investigated for COVID-19 treatment than 2019; including hydroxychloroquine (+563%, 95% confidence interval [CI]: 5.87, 7.48) and azithromycin (+150%, 95% CI: 2.37, 2.63). Ceftriaxone prescribing also increased (+43%, 95% CI: 1.34, 1.54). Prescribing of dexamethasone was 36% lower in April (95% CI:.55,.73) and 303% higher in July (95% CI: 3.66, 4.45). Although azithromycin and ceftriaxone prescribing increased, total antibiotic prescribing among residents was lower from May (−5%, 95% CI:.94,.97) through October (−4%, 95% CI:.94,.97) in 2020 compared to 2019. Conclusions During the pandemic, large numbers of residents were prescribed drugs investigated for COVID-19 treatment, and an increase in prescribing of antibiotics commonly used for respiratory infections was observed. Prescribing of these drugs may increase the risk of adverse events, without providing clear benefits. Surveillance of NH prescribing practices is critical to evaluate concordance with guideline-recommended therapy and improve resident safety. [ABSTRACT FROM AUTHOR]

Background: Jurisdictions participating in Strengthening the US Response to Resistant Gonorrhea (SURRG) implemented specimen collection for culture and antimicrobial susceptibility testing from a sample of persons of all genders (at multiple anatomic sites) attending sexually transmitted disease clinics and community clinics. We describe the percentage and characteristics of patients whose isolates demonstrated reduced susceptibility (RS) to azithromycin, ceftriaxone, or cefixime.Methods: We included patients from clinics that participated in SURRG whose isolates underwent antimicrobial susceptibility testing by Etest. We defined RS as azithromycin minimum inhibitory concentrations (MICs) ≥2 μg/mL (AZM-RS), ceftriaxone MICs ≥0.125 μg/mL (CRO-RS), or cefixime MICs ≥0.25 μg/mL (CFX-RS). Patients with repeated infections appeared >1 time in the data. We calculated the frequency and percentage of patients with an isolate demonstrating RS by epidemiological characteristics.Results: During the period 2018-2019, 10,013 patients from 8 jurisdictions provided 10,735 isolates. Among 10,013 patients, 11.0% (n = 1099) had ≥1 isolate with AZM-RS (range by jurisdiction, 2.5%-18.0%). Approximately 11.3% of 8771 of patients visiting sexually transmitted disease clinics and approximately 8.8% of 1242 patients visiting community clinics had an AZM-RS isolate. Nearly 6% of 1013 females had an AZM-RS isolate; among males, the percents of patients with an AZM-RS isolate were 17.7% among 4177 men who have sex only with men and 6.1% among 3581 men who have sex only with women. Few (0.4%) patients had isolates with CFX-RS (n = 40) or CRO-RS (n = 43).Conclusions: Although infections with reduced cephalosporin susceptibility were rare, AZM-RS infections were prevalent in this sample of patients in multiple jurisdictions and across gender and gender of sex partner categories. [ABSTRACT FROM AUTHOR]

We assessed the overseas gonorrhea results reported in the CDC's Electronic Disease Notification (EDN) system among refugees ≥ 15 years old who arrived in the United States during 2018. Of 18,720 refugees, 57 (0.4%) tested positive. Among those with a positive test, 31 (54.5%) were born in the Democratic Republic of the Congo, followed by 12 (21.1%) from Afghanistan. Thirty-three (57.9%) cases were female. Fifty-one cases (89.4%) were between 15 and 44 years of age; 25 (43.9%) were ages 15–24 and 26 (45.6%) were ages 25–44. Among the cases, 56 (98.2%) were treated overseas with the recommended therapy of ceftriaxone and azithromycin. Our findings suggest that the risk of gonorrhea in refugees is similar to that in the U.S. Given recent worldwide increases in gonorrhea, additional monitoring among refugees are necessary to assess the appropriateness of the gonorrhea screening requirement in the overseas medical examination. [ABSTRACT FROM AUTHOR]

Background Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. Methods We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC's National Antimicrobial Resistance Monitoring System from 1999 through 2015. Results 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0–50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). Conclusions Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ among patients hospitalized with COVID-19. We examined the effects of HCQ alone and in combination with azithromycin in a hospitalized population of US veterans with COVID-19, using a propensity score–adjusted survival analysis with imputation of missing data. According to electronic health record data from the US Department of Veterans Affairs health care system, 64,055 US Veterans were tested for the virus that causes COVID-19 between March 1, 2020 and April 30, 2020. Of the 7,193 veterans who tested positive, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and there was an increased risk of intubation when HCQ was used in combination with azithromycin (hazard ratio = 1.55; 95% confidence interval: 1.07, 2.24). In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treatment of patients hospitalized with COVID-19, using a national sample of the US veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ. [ABSTRACT FROM AUTHOR]

Salmonella enterica subspecies enterica serotype Dublin is a host-adapted serotype in cattle, associated with enteritis and systemic disease. The primary clinical manifestation of Salmonella Dublin infection in cattle, especially calves, is respiratory disease. While rare in humans, it can cause severe illness, including bacteremia, with hospitalization and death. In the United States, S. Dublin has become one of the most multidrug-resistant serotypes. The objective of this study was to characterize S. Dublin isolates from sick cattle by analyzing phenotypic and genotypic antimicrobial resistance (AMR) profiles, the presence of plasmids, and phylogenetic relationships. S. Dublin isolates (n = 140) were selected from submissions to the NVSL for Salmonella serotyping (2014–2017) from 21 states. Isolates were tested for susceptibility against 14 class-representative antimicrobial drugs. Resistance profiles were determined using the ABRicate with Resfinder and NCBI databases, AMRFinder and PointFinder. Plasmids were detected using ABRicate with PlasmidFinder. Phylogeny was determined using vSNP. We found 98% of the isolates were resistant to more than 4 antimicrobials. Only 1 isolate was pan-susceptible and had no predicted AMR genes. All S. Dublin isolates were susceptible to azithromycin and meropenem. They showed 96% resistance to sulfonamides, 97% to tetracyclines, 95% to aminoglycosides and 85% to beta-lactams. The most common AMR genes were: sulf2 and tetA (98.6%), aph(6)-Id (97.9%), aph(3")-Ib, (97.1%), floR (94.3%), and blaCMY-2 (85.7%). All quinolone resistant isolates presented mutations in gyrA. Ten plasmid types were identified among all isolates with IncA/C2, IncX1, and IncFII(S) being the most frequent. The S. Dublin isolates show low genomic genetic diversity. This study provided antimicrobial susceptibility and genomic insight into S. Dublin clinical isolates from cattle in the U.S. Further sequence analysis integrating food and human origin S. Dublin isolates may provide valuable insight on increased virulence observed in humans. [ABSTRACT FROM AUTHOR]

Background The objective of our study was to describe trends in US outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017–2019). Methods We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies from January 2017 through May 2020. We averaged estimates from 2017 through 2019 and defined expected seasonal change as the average percent change from January to May 2017–2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017–2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. Results From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017–2019 versus 2020 were observed in April (–39%) and May (–42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. Conclusions From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected because of seasonal trends alone, possibly related to the coronavirus disease 2019 pandemic and associated mitigation measures. [ABSTRACT FROM AUTHOR]

This article describes an 18-year-old immunocompetent patient who developed Mycobacterium kansasii , manifested with shortness of breath and a cavitary lung lesion seen on radiograph. Initial sputum smears were negative; however, after 2 weeks, the cultures grew M. kansasii and the patient was started on an antimycobacterial regimen. [ABSTRACT FROM AUTHOR]

The rapid expansion of telemedicine has highlighted challenges and opportunities to improve antibiotic use and effectively adapt antibiotic stewardship best practices to outpatient telemedicine settings. Antibiotic stewardship integration into telemedicine is essential to optimize antibiotic prescribing for patients and ensure health care quality. We performed a narrative review of published literature on antibiotic prescribing and stewardship in outpatient telemedicine to inform the adaptation of the Core Elements of Outpatient Antibiotic Stewardship framework to outpatient telemedicine settings. Our narrative review suggests that in-person antibiotic stewardship interventions can be adapted to outpatient telemedicine settings. We present considerations for applying the Core Elements of Outpatient Antibiotic Stewardship to outpatient telemedicine which builds upon growing evidence describing care delivery and quality improvement in this setting. Additional applied implementation research is necessary to inform the application of effective, sustainable, and equitable antibiotic stewardship interventions across the spectrum of outpatient telemedicine.

Background: Antibiotic use is a significant risk factor associated with Clostridioides difficile (C difficile) infection (CDI). Community-acquired pneumonia (CAP) is a common infection leading to hospital admission and the use of antibiotics that are highly associated with CDI. It has been proposed that doxycycline, a tetracycline antibiotic, may be protective against CDI., Methods: A retrospective analysis was conducted in hospitalized patients in Veterans Affairs Hospitals across the United States to determine if doxycycline was associated with a decreased risk of CDI. The primary outcome was the development of CDI within 30 days of initiation of doxycycline or azithromycin, as part of a standard pneumonia regimen., Results: Approximately 156,107 hospitalized patients who received care at a Veterans Affairs Hospital and were diagnosed with CAP during the study timeframe were included. A 17% decreased risk of CDI was identified with doxycycline compared to azithromycin when used with ceftriaxone for the treatment of pneumonia (P = .03). In patients who had a prior history of CDI, doxycycline decreased the incidence of CDI by 45% (odds ratio 0.55; P = .02)., Conclusions: Doxycycline is associated with a lower risk of CDI compared to azithromycin when used for atypical coverage in CAP. Thus, patients who are at such risk may benefit from doxycycline as a first-line agent for atypical coverage, rather than the use of a macrolide antibiotic, if Legionella is not of concern., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

In April 2020, there were significant reductions in prescription fills of each of the 10 most prescribed outpatient antibiotics in the United States. Monthly azithromycin, amoxicillin-clavulanate, and levofloxacin fills did not rebound significantly from April through July 2020. Coronavirus disease 2019 had an immediate and sustained impact on US outpatient antibiotic prescribing. [ABSTRACT FROM AUTHOR]

Purpose The global coronavirus disease 2019 (COVID-19) pandemic and the search for ways in which to provide the best available care have created unprecedented times in terms of rapidly evolving reports of available treatment options. The primary objective of our analysis was to categorize online, open-source guidance to determine how US institutions approached their recommendations for management of patients with COVID-19 in the early weeks of the pandemic. Methods A search for open-source, online institutional guidelines for the treatment of COVID-19 was conducted using predefined criteria. The search was limited to the United States and conducted from April 12 through 14, 2020, and again on April 22, 2020. Searches were conducted at 2 points in time in order to identify changes in treatment recommendations due to evolving literature or institutional experience. Treatment recommendations, including guidance on antiviral therapy, corticosteroid and interleukin-6 inhibitor use, and nutritional supplementation were compared. Results Of the 105 institutions that met initial screening criteria, 14 institutions (13.3%) had online COVID-19 guidance available. Supportive care and clinical trial enrollment were the primary recommendations in all evaluated guidance. Recommendations to consider antimicrobial and adjunctive therapy varied. Eighty-six percent of guidelines contained recommendations for use, or consideration of use, of hydroxychloroquine. Guidance from 2 institutions mentioned use of hydroxychloroquine and azithromycin in combination. Of the 13 institutions listing hydroxychloroquine dosing recommendations, 62% recommended maintenance dosing of 200 mg twice daily. Infectious diseases or other specialty consultation was required by 89% of institutions using interleukin-6 inhibitors for COVID-19 management. Conclusion Overall, the analysis revealed variability in treatment or supplemental pharmacologic therapy for the management of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Antibiotic-resistant gonorrhoea has been a chronic public health burden since the mid-1930s. Recent emergence of isolates resistant to the current recommended antibiotics for gonorrhoea further magnifies the threat of untreatable gonorrhoea. The lack of new, effective antibiotics highlights the need for better understanding of the population structure of Neisseria gonorrhoeae in order to provide greater insight on how to curtail the spread of antimicrobial-resistant N. gonorrhoeae.Objectives: To explore a potential application of MALDI-TOF MS to differentiate N. gonorrhoeae displaying different levels of susceptibility to the antibiotic azithromycin.Methods: We conducted MALDI-TOF MS using the Bruker Biotyper on 392 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project (GISP) and/or the Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. The MALDI-TOF MS spectra were visually analysed to assess the presence of distinctive peak(s). Statistical analysis was performed to assess the relationship between gonococcal isolates with the distinct protein peak and antibiotic susceptibility.Results: In this study, we were able to differentiate N. gonorrhoeae isolates into two distinct subpopulations using MALDI-TOF MS. Isolates were distinguished by the presence or absence of a spectral peak at 11 300 Da. Notably, these two groups exhibited different levels of susceptibility to azithromycin.Conclusions: We have shown that in addition to its ability to identify N. gonorrhoeae, MALDI-TOF MS could also be used to differentiate gonococcal isolates with different levels of susceptibility to azithromycin. [ABSTRACT FROM AUTHOR]

Acne vulgaris is the most common dermatological disease in the United States, affecting up to 85 percent of teenagers. While the American Academy of Dermatology has established guidelines regarding acne treatment in general, the variability among acne treatments, even within a given class, prevents establishment of a straightforward regimen. For example, moderate to severe acne is generally treated with an oral antibiotic, although several options are available-both across and within antibiotic classes. The aim of this review is to report the efficacy and safety data available for commonly prescribed oral antibiotics. While there are currently no data to support superiority of one drug over another, there are substantial differences in safety profiles and brand-specific features that may make one antibiotic preferable over another. [ABSTRACT FROM AUTHOR]

Importance: Macrolides of different ring sizes are critically important antimicrobials for human medicine and veterinary medicine, though the widely used 15-membered ring azithromycin in humans is not approved for use in veterinary medicine. We document here the emergence of azithromycin-resistant Salmonella among the NARMS culture collections between 2011 and 2021 in food animals and retail meats, some with co-resistance to ceftriaxone or decreased susceptibility to ciprofloxacin. We also provide insights into the underlying genetic mechanisms and genomic contexts, including the first report of a novel combination of azithromycin resistance determinants and the characterization of multidrug-resistant plasmids. Further, we highlight the emergence of a multidrug-resistant Salmonella Newport clone in food animals (mainly cattle) with both azithromycin resistance and decreased susceptibility to ciprofloxacin. These findings contribute to a better understating of azithromycin resistance mechanisms in Salmonella and warrant further investigations on the drivers behind the emergence of resistant clones., Competing Interests: The authors declare no conflict of interest.

• Resistant R. equi is highly prevalent and widespread in horse-breeding farms in Kentucky. • Resistance is associated with density of animals and the number of animals treated with antimicrobials. • Resistant isolates in the environment can serve as a repository for dissemination of resistance genes. The combination of a macrolide and rifampicin has been the mainstay of therapy in foals with Rhodococcus equi pneumonia for decades. Recent studies suggest that mass antimicrobial treatment of subclinically affected foals over time has selected for antimicrobial resistance. Our objective was to estimate the prevalence of R. equi strains resistant to macrolides and rifampicin at horse breeding farms in Kentucky. A hundred breeding farms in Kentucky were surveyed and R. equi were cultured from soil samples. Data were analyzed with logistic regression and generalized linear modeling (P < 0.05). Seventy-six percent (76%) of farms yielded resistant R. equi , and resistance to macrolides and rifampicin was associated with their use at farms. The present study is the first to report the prevalence and distribution of resistant isolates in the environment of farms in Kentucky, USA. Collectively, previous reports and the data presented herein provide irrefutable evidence of emerging antimicrobial resistance in R. equi with alarming prevalence. Widespread dissemination and maintenance of resistance genes in the environment where many other pathogenic bacteria exist is a concern for both animal and human health. [ABSTRACT FROM AUTHOR]

Objectives: A multicenter, randomized controlled trial has demonstrated the benefit of adding azithromycin to routine preoperative antibiotics in unscheduled cesarean deliveries (CDs) to prevent surgical site infections. We sought to describe and identify barriers to the implementation of azithromycin prophylaxis for CDs by Alabama healthcare providers.Methods: We conducted an online, self-administered survey of obstetrics and gynecology (OB/GYN) providers in Alabama. E-mail addresses were obtained from a publicly available list. We sent an invitation to complete an anonymous online survey to 478 providers after excluding incompatible addresses and providers who previously opted out of the survey platform. After the initial survey, three reminders to complete the survey were sent. Standard questions regarding population and provider demographics were asked. We assessed timing, duration, and type of antibiotic used for scheduled cesareans and unscheduled (labor) cesareans, and the reasons for not using azithromycin for prophylaxis. Results were compared using the Student t test and χ2 test as appropriate.Results: Of the 66 OB/GYN providers who responded to the survey, 44 (66.7%) performed CDs. Most providers (59.1%) identified as female, served a mix of urban and rural communities (54.5%), and performed deliveries at a level IV hospital (54.5%) with >2000 deliveries annually (52.3%). Most providers (77.3%) reported that an antibiotic stewardship committee supervised antibiotic use at their hospital. For unscheduled cesareans, 54.5% reported the use of azithromycin and 47.7% for scheduled cesareans. The most common reason for not currently using azithromycin was being unaware of evidence for its use (55.6%). The only factors associated with azithromycin use were the urban/rural mix of the provider's patient population (P = 0.03) and the hospital level (P < 0.01). More providers serving a primarily urban population reported azithromycin use (87.5%) compared with those serving in a rural (33.3%) or mixed (47.6%) population. In addition, 74.2% of the obstetricians who delivered in a level 3 or 4 hospital reported using azithromycin prophylaxis, whereas only 22.2% of level 1 or 2 hospital providers reported this usage.Conclusions: Only 56.8% of Alabama obstetrics providers reported using azithromycin for CD, which is both effective and cost saving for prevention of surgical site infections. More needs to be done to increase awareness of these benefits. [ABSTRACT FROM AUTHOR]

Human babesiosis continues to spread in multiple regions of the US. It is transmitted by Ixodes species ticks, as are Lyme disease and anaplasmosis. Its variable clinical presentations, together with serologic detection limitations, require that a high index of clinical suspicion be present for prompt diagnosis. This article discusses case examples showing the wide range of symptoms and presentations that are possible with babesiosis. [ABSTRACT FROM AUTHOR]

Objectives: To characterize antibiotics prescribed to older adults to guide efforts to improve antibiotic use. Design: Descriptive analysis. Setting: Ambulatory. Participants: Adults aged 65 and older in the United States. Measurements: Information on outpatient antibiotic prescriptions dispensed for older adults from 2011 to 2014 was extracted from the IQVIA Xponent database. A chi‐square trend analysis was conducted to assess annual changes in antibiotic prescribing rates. A descriptive analysis of prescribing rates by antibiotic, age group, sex, state, Census region, and provider specialty was conducted. Results: From 2011 to 2014, outpatient antibiotic prescribing rates remained stable in older U.S. adults (P =.89). In 2014, older adults were dispensed 51.6 million prescriptions (1,115 prescriptions/1,000 persons). Persons aged 75 and older had a higher prescribing rate (1,157 prescriptions/1,000 persons) than those aged 65 to 74 (1,084 prescriptions/1,000 persons). Prescribing rates were highest in the South 1228 prescriptions/1,000 persons) and lowest in the West (854 prescriptions/1,000 persons). The most commonly prescribed class was quinolones, followed by penicillins and macrolides. Azithromycin was the most commonly prescribed drug, followed by amoxicillin and ciprofloxacin. Internists and family physicians prescribed 43% of antibiotic courses. Conclusion: On average, in 2014, U.S. adults aged 65 and older received enough outpatient antibiotic courses for every older adult to receive at least 1. Quinolones and azithromycin are potential targets for assessing the appropriateness of antibiotic prescribing in this population. Interventions to improve use targeting internists and family physicians in the South Census region might have the potential to have the greatest effect. [ABSTRACT FROM AUTHOR]

Guideline-based management of asthma was developed as a means of standardizing asthma therapies and of improving outcomes. The National Asthma Education and Prevention Program and the Global Initiative for Asthma guidelines provide recommendations to care providers about the routine management of asthma. There has been rapid development of new therapies for asthma, specifically with the advent of new drug delivery devices and biologic therapies for severe asthma. We are increasingly recognizing that asthma is a heterogenous disease with a diverse underlying pathophysiology, and therefore, it is imperative for care providers to begin to understand asthma phenotypes and endotypes, and the implications of these classifications on management, especially of severe refractory asthma. This article serves as a review of guideline-based therapy for asthma and includes updates on alternative therapies, new approaches that use previously recognized therapies, and special populations with asthma. [ABSTRACT FROM AUTHOR]

Background: The Centers for Disease Control and Prevention 2015 Sexually Transmitted Disease Treatment Guidelines recommend that clinicians consider cephalosporin treatment failure in patients who deny interval sexual exposure and are nucleic acid amplification test (NAAT) positive for Neisseria gonorrhoeae (NG) at least 7 days after adequate treatment. We evaluate the real-world implications of the interval the Centers for Disease Control and Prevention recommends for a NAAT test-of-cure (TOC), by ascertaining the frequency of NG NAAT positivity at different anatomic sites among men who have sex with men (MSM) at TOC 7 to 30 days after treatment.Methods: We analyzed data from the medical records of MSM with laboratory-confirmed NG who were presumptively treated for NG during the period from June 2013 to April 2016 and returned for a TOC visit within 30 days. Data examined included symptoms, site of NG specimen collection, treatment regimen, follow-up testing, and intervening sexual activity.Results: There were 1027 NG-positive specimens obtained from 763 MSM patients at 889 presumptive treatment visits. Of these, 44% (337/763) MSM returned for 1 or more TOC visits, and 413 specimens were collected a median of 10 days after presumptive treatment. Three percent (14/413) of specimens collected were NG NAAT positive at TOC a median of 13 days after treatment: 5% (12/256) of urethral specimens, 1% (1/147) of anorectal specimens (P = 0.037, urethral vs. anorectal), and 10% (1/10) of oropharyngeal specimens (P = 0.40, urethral vs. oropharyngeal).Conclusions: A small percent of patients were NG NAAT positive at TOC. Compared with anorectal specimens, urethral specimens were more frequently still positive at TOC. A large proportion of MSM will return for a TOC visit as part of standard clinical care. [ABSTRACT FROM AUTHOR]

Little is known about how COVID-19 treatment patterns have evolved over time in nursing homes (NHs) despite the devastating effects of COVID-19 in this setting. The aim was to describe changes in COVID-19–related medication use over time among NH residents in the United States. Retrospective cohort study. This study used electronic health records (EHR) from 11 different US NH corporations between January 1, 2018, and March 31, 2022. The use of medications approved for COVID-19–related conditions or known to be used off-label for COVID-19 during the study period is identified. We described trends in the use of each drug and combined use per 1000 NH residents over calendar time [quarters (Q)]. A total of 59,022 unique residents with the use of an eligible medication were identified. Hydroxychloroquine use sharply increased from 9.8 in 2020Q1 to 30.2 orders per 1000 individuals in 2020Q2. Dexamethasone use increased sharply from 14.8 in 2020Q2 to a peak of 121.9 orders per 1000 individuals in 2020Q4. Azithromycin use increased from 44.1 in 2019Q3 to a peak of 99.9 orders per 1000 individuals in 2020Q4, with a drop in 2020Q3 of 51.3 per 1000 individuals in 2020Q3. Concurrent use of azithromycin and hydroxychloroquine increased sharply from 0.3 in 2020Q1 to 10.6 orders per 1000 residents in 2020Q2 and then drastically decreased to 0.6 per 1000 residents in 2020Q3. Concurrent use of dexamethasone and azithromycin rose considerably from 0.7 in 2020Q2 to 28.2 orders per 1000 residents in 2020Q4. As in other settings, COVID-19–related medication use in NHs appears to have changed in response to the shifting evidence base and availability of medications during the pandemic. Providers should continue to diligently modify their prescribing as new evidence accrues. [ABSTRACT FROM AUTHOR]

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline. [ABSTRACT FROM AUTHOR]

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline. [ABSTRACT FROM AUTHOR]

B Introduction: b Observation reports have suggested macrolides, such as azithromycin (AZI), may be used as immunomodulation for pediatric acute asthma exacerbations. Prospective clinical trials are needed to assess clinical and molecular efficacy endpoints of AZI immunomodulation in pediatric CA. [Extracted from the article]

Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006-2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47-4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04-0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method. [ABSTRACT FROM AUTHOR]

Rationale: The natural history of lung function in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant is poorly characterized. Understanding the trajectory of lung function is necessary for prompt clinical recognition and treatment and also for the rational design of prospective studies.Objectives: To describe the longitudinal trajectory of lung function parameters, including FEV1, in patients with BOS after hematopoietic cell transplant.Methods: Subjects with BOS defined by National Institutes of Health consensus guidelines criteria from a recent multicenter prospective trial of combination treatment with fluticasone, azithromycin and montelukast and a retrospective cohort from Fred Hutchinson Cancer Research Center were included. Longitudinal change in FEV1 for each patient was calculated on the basis of available pulmonary function tests in three periods: pre-BOS, from BOS diagnosis to 6 months, and 6-18 months after diagnosis. The effect of treatment on FEV1 trajectory was analyzed by univariate and multivariate linear regression. The Kaplan-Meier method was used to estimate survival.Measurements and Main Results: The FEV1 percent predicted value at diagnosis was 46% (interquartile range, 35-57%) for trial participants and 53% (interquartile range, 41-64%) for the retrospective cohort. There was a concomitant mild reduction in FVC, as well as a marked reduction in forced expiratory flow, midexpiratory phase, at diagnosis. While there was individual heterogeneity, the overall FEV1 trajectory was characterized by a marked decline within 6 months prior to BOS diagnosis, followed by stability of FEV1 early after diagnosis and a slow rate of decline beyond 6 months. The effect of the trial medications on FEV1 trajectory after BOS diagnosis was a mean rate of change of 0.92% predicted per month (95% confidence interval, -0.53 to 2.37) compared with the retrospective cohort, but this was not statistically significant. Two-year overall survival rates were 76% and 72% for the study participants and the retrospective cohort patients, respectively. Earlier time to diagnosis after hematopoietic cell transplant and severity of FVC at diagnosis were significantly associated with reduced survival.Conclusions: The FEV1 trajectory in patients with BOS after hematopoietic cell transplant in a contemporary era of management follows a predominant pattern of rapid FEV1 decline in the 6 months prior to diagnosis, followed by FEV1 stabilization after diagnosis. [ABSTRACT FROM AUTHOR]

OVERVIEW: Sexually transmitted infections (STIs) are the most common infectious diseases in the United States. They have enormous human consequences, including severe reproductive complications, neonatal injury, and death; and because STIs are associated with social stigma, they also have substantial psychological impact. The economic consequences are also enormous: it's estimated that STIs cost the nation about $ 16 billion in annual health care costs. All communities are affected, although significant racial, ethnic, and other disparities persist. Nurses play a critical role in educating patients on STIs, screening for disease, and providing treatment. Nurses can also help minimize the impact of social stigma by providing informed, confidential, and sensitive care, and by promoting sexual health. This article provides an overview of the symptoms, screening methods, and treatment recommendations for the most common STIs in the United States and describes the most recent relevant findings in order to inform nursing practice. [ABSTRACT FROM AUTHOR]

Tick-borne infections are seen throughout the United States, with varying geographical locations. Many of these infections are also increasingly seen in Europe. Certain ticks (egIxodes) can transmit more than one infection. Diagnosis, particularly in early infection, can be challenging and therefore knowledge of the distinguishing clinical features and epidemiology of these diseases is important. Testing for Lyme disease often causes confusion for patients and medical providers, as serological tests may be negative in early infection and conversely may be positive for years after infection. Newer tests, such as the C6 ELISA, may play a role in Lyme diagnosis. Additionally, the value of a simple blood film should not be underestimated for diagnosing babesiosis and anaplasmosis. In certain situations, empiric therapy may be required for tick-borne infections as severe illness with multiorgan failure can occur, particularly in older and immunocompromised hosts. This review describes the more commonly seen tick-borne infections: Lyme, babesiosis, anaplasmosis and Rocky Mountain Spotted Fever. More recently identified tick-borne infections, such as southern tick-associated rash illness and Borrelia miyamotoi, are also covered. [ABSTRACT FROM AUTHOR]

Objective The aim of the article is to provide an update on medication use in infants admitted to the neonatal intensive care unit (NICU) in the United States and examine how use has changed over time. Study Design We performed a retrospective review (2005-2010) of a large prospectively collected administrative database. Result Medications most commonly administered during the study period were ampicillin, gentamicin, caffeine citrate, vancomycin, beractant, furosemide, fentanyl, dopamine, midazolam, and calfactant (56-681 exposures per 1,000 infants). Those with the greatest relative increase in use included azithromycin, sildenafil, and milrinone. Medications with the greatest relative decrease in use included theophylline, metoclopramide, and doxapram. Conclusion Medication use in the NICU has changed substantially over time, and only 35% of the most commonly prescribed medications are Food and Drug Administration -approved in infants. [ABSTRACT FROM AUTHOR]

Abstract: Drug-induced phospholipidosis (PLD) is a common adverse effect which has led to the termination of clinical trials for many candidate pharmaceuticals. However, this lipid-inducing effect may be beneficial in the treatment of meibomian gland dysfunction (MGD). MGD is the major cause of dry eye disease (DED), which affects 40 million people in the USA and has no cure. Azithromycin (AZM) is a PLD-inducing antibiotic that is used off-label to treat MGD, and is presumably effective because it suppresses the MGD-associated conjunctival inflammation (i.e. posterior blepharitis) and growth of lid bacteria. We hypothesize that AZM can act directly to promote the function of human meibomian gland epithelial cells by inducing PLD in these cells, characterized by the accumulation of lipids and lysosomes. Immortalized human meibomian gland epithelial cells (HMGEC) were cultured with or without azithromycin for 5 days. Cells were evaluated for cholesterol (Filipin) and neutral lipid (LipidTox) staining, as well as the appearance of lysosomes (LysoTracker) and lamellar bodies (transmission electron microscopy, TEM). The lipid composition of cellular lysates was analyzed by high performance thin-layer chromatography. Our findings demonstrate that AZM stimulates the accumulation of free cholesterol, neutral lipids and lysosomes in HMGEC. This AZM-induced increase of neutral lipid content occurred predominantly within lysosomes. Many of these vesicles appeared to be lamellar bodies by TEM, which is the characteristic of PLD. Our findings also show that AZM promotes an accumulation of free and esterified cholesterol, as well as phospholipids in HMGECimmortalized. Our results support our hypothesis and confirm the beneficial effect of PLD induced by AZM on HMGEC. Our discovery reveals a new potential use of PLD-inducing drugs, and makes this adverse effect a beneficial effect. [Copyright &y& Elsevier]

Background Population pharmacokinetics (PK) of azithromycin (AZ) and chloroquine (CQ) following administration of fixed-dose combination tablet formulations of AZ and CQ (AZCQ) was evaluated using data from two studies: 1) in children with symptomatic uncomplicated falciparum malaria in sub-Saharan Africa; and 2) in healthy adults in the United States. Methods Study 1 included paediatric subjects randomized to either AZCQ or artemether-lumefantrine treatment in Cohort 1 (age 5-12 years) and Cohort 2 (age 6-59 months). Dosing of AZCQ was approximately 30 mg/kg AZ and 10 mg/kg CQ once daily for 3 days (for ⩾20 kg weight: AZ/CQ 300/100 mg per tablet; 5 to <20 kg weight: AZ/CQ 150/50 mg per tablet). Study 2 included adults randomized to receive either two AZCQ tablets (AZ/CQ 250/155 mg per tablet) or individual commercial tablets of AZ 500 mg and CQ 300 mg. Serum AZ and plasma CQ concentrations from both studies were pooled. Population PK models were constructed using standard approaches to evaluate the concentration-time data for AZ and CQ and to identify any covariates predictive of PK behaviour. Results A three-compartment PK model with linear clearance and absorption adequately described AZ data, while a two-compartment model with linear clearance and absorption and an absorption lag adequately described CQ data. No overall bias or substantial model misspecification was evident using diagnostic plots and visual predictive checks. Body weight as an allometric function was the only covariate in the final AZ and CQ PK models. There were significantly lower AZ (0.488 vs 0.745 [mg·h/L]/[mg/kg], p < 0.00001) and CQ (0.836 vs 1.27 [mg.h/L]/[mg/kg], p < 0.00001) exposures (AUCinf) normalized by dose (mg/kg) in children compared with the adults. Conclusions The PK of AZ and CQ following administration of AZCQ was well described using a threeand two-compartment model, respectively. AZ and CQ exhibited linear absorption and clearance; the model for CQ included an absorption lag. Weight was predictive of exposure for both AZ and CQ. Assuming equivalent dosing (mg/kg), AZ and CQ exposure in children would be expected to be lower than that in adults, suggesting that children may require a higher dose (mg/kg) than adults to achieve the same AZ and CQ exposure. [ABSTRACT FROM AUTHOR]

Objective: The risk of retinal detachment (RD) following exposure to fluoroquinolone (FQ) has been assessed in multiple studies, however, results have been mixed. This study was designed to estimate the risk of RD following exposure to FQ, other common antibiotics, and febrile illness not treated with antibiotics (FINTA) using a self-controlled case series (SCCS) study design to reduce risk of confounding from unreported patient characteristics., Design: Retrospective database analysis-SCCS., Setting: Primary and Secondary Care., Study Population: 40,981 patients across 3 US claims databases (IBM® MarketScan® commercial and Medicare databases, Optum Clinformatics)., Outcome: RD., Methods: Exposures included FQ as a class of drugs, amoxicillin, azithromycin, trimethoprim with and without sulfamethoxazole, and FINTA. For the primary analysis, all drug formulations were included. For the post hoc sensitivity analyses, only oral tablets were included. Risk windows were defined as exposure period (or FINTA duration) plus 30 days. Patients of all ages with RD and exposures in 3 US claims databases between 2012 to 2017 were included. Diagnostics included p value calibration and pre-exposure outcome analyses. Incidence rate ratios (IRR) and 95% confidence interval (CI) comparing risk window time with other time were calculated., Results: Our primary analysis showed an increased risk for RD in the 30 days prior to exposure to FQ or trimethoprim without sulfamethoxazole. This risk decreased but remained elevated for 30 days following first exposure. Our post-hoc analysis, which excluded ophthalmic drops, showed no increased risk for RD at any time, with FQ and other antibiotics., Conclusion: Our results did not suggest an association between FQ and RD. Oral FQ was not associated with an increased risk for RD during the pre- or post-exposure period., Trial Registration: ClinicalTrials.gov identifier: NCT03479736-March 21, 2018., Competing Interests: At the time of the work, all authors were full-time employees of Janssen Research & Development, LLC, which is the Marketing Authorisation Holder for Levaquin (a fluoroquinolone) in the United States and some other countries. As full-time employees, the authors held stock or stock options. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007-2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability of treatment weighted survival models, we estimated hazard ratios, risk differences, and 95% confidence intervals. The azithromycin vs. amoxicillin-based antibiotic cohort included 282,899 patients and 725,431 treatment episodes (381,306 azithromycin and 344,125 amoxicillin-based episodes). Azithromycin vs. amoxicillin-based antibiotic treatment was associated with higher relative and absolute risks of sudden cardiac death, weighted hazard ratio of 1.70 (95% Confidence Interval, 1.36 to 2.11) and weighted risk difference per 100,000 treatment episodes of 25.0 (15.5 to 36.5). The azithromycin vs. levofloxacin cohort included 245,143 patients and 554,557 treatment episodes (387,382 azithromycin and 167,175 levofloxacin episodes). Azithromycin vs. levofloxacin treatment was associated with lower relative and absolute risks of sudden cardiac death, weighted hazard ratio of 0.79 (0.64 to 0.96) and weighted risk difference per 100,000 treatment episodes of -18.9 (-35.5 to -3.8). Thus, when selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Azithromycin (Zithromax) is an azalide antibiotic that binds to the 50S ribosomal subunit of the susceptible organism and thereby interferes with its protein synthesis. An open-label, randomized, single-dose, 3-way crossover bioequivalence study was conducted to compare the rate and extent of absorption of the azithromycin 250-mg tablet manufactured at Pfizer Dalian (China) and that at Pfizer Barceloneta (United States) under fasted and fed conditions in healthy Chinese subjects. This study aimed to support a generic consistency evaluation program, initiated by the National Medical Products Administration, for evaluating the quality and efficacy of the products manufactured in China. In the study, the within-subject standard deviation for area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fasted condition was <0.294, and the 90%CI for the ratio was within 80% to 125%; the within-subject SDs for serum peak concentration in the fasted condition, area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fed condition, and serum peak concentration in the fed condition, were all >0.294, with the upper confidence bounds being <0.00, and the point estimates of the ratios being within 80% to 125%. The results support the bioequivalence between azithromycin tablets manufactured in China and the United States in fasted and fed conditions, with both tablets showing an acceptable safety/tolerability profile in the studied population., (© 2022 Pfizer (China) Research and Development Co. Ltd. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)