Covalent penicillin-protein conjugates elicit anti-drug antibodies that are clonally and functionally restricted.

Many archetypal and emerging classes of small-molecule therapeutics form covalent protein adducts. In vivo, both the resulting conjugates and their off-target side-conjugates have the potential to elicit antibodies, with implications for allergy and drug sequestration. Although ß-lactam antibiotics are a drug class long associated with these immunological phenomena, the molecular underpinnings of off-target drug-protein conjugation and consequent drug-specific immune responses remain incomplete. Here, using the classical ß-lactam penicillin G (PenG), we probe the B and T cell determinants of drug-specific IgG responses to such conjugates in mice. Deep B cell clonotyping reveals a dominant murine clonal antibody class encompassing phylogenetically-related IGHV1, IGHV5 and IGHV10 subgroup gene segments. Protein NMR and x-ray structural analyses reveal that these drive structurally convergent binding modes in adduct-specific antibody clones. Their common primary recognition mechanisms of the penicillin side-chain moiety (phenylacetamide in PenG)-regardless of CDRH3 length-limits cross-reactivity against other ß-lactam antibiotics. This immunogenetics-guided discovery of the limited binding solutions available to antibodies against side products of an archetypal covalent inhibitor now suggests future potential strategies for the 'germline-guided reverse engineering' of such drugs away from unwanted immune responses.

Ischaemic apoplexy caused by syphilis.

Syphilis is a sexually transmitted disease caused by the spirochaete Treponema pallidum. Patients with untreated syphilis can develop meningovascular syphilis at any stage of the disease. This is a case report of a 44-year-old man displaying two instances of acute vertigo and lateralized paraesthesia. MRI showed infarctions in the left thalamus and capsula interna. Subsequent investigations including cerebral spinal fluid analysis revealed a diagnosis of neurosyphilis. The patient was treated intravenously with benzylpenicillin and ceftriaxone with complete clinical remission.

Catching the Culprit: Benzylpenicillin Neurotoxicity Confirmed by Therapeutic Drug Monitoring in a Critically Ill Patient With Continuous Venovenous Hemofiltration.

ABSTRACT: We present the case of a 65-year-old patient who was treated with high-dose benzylpenicillin for severe invasive pneumococcal pneumonia, complicated by acute renal failure managed with continuous venovenous hemofiltration. After cessation of continuous venovenous hemofiltration, the patient experienced multiple tonic-clonic seizures. Therapeutic drug monitoring revealed high total serum concentrations of benzylpenicillin, identifying it as the likely cause of the neurotoxicity. This case study presents the first documented total serum benzylpenicillin concentration associated with neurotoxicity.

Clinical characteristics and outcomes of people living with HIV and ocular syphilis during the COVID-19 health emergency.

BACKGROUND: The global shift in healthcare during the COVID-19 pandemic led to challenges in the care of people living with HIV. METHODS: We conducted a retrospective study that aimed to delineate sociodemographic, clinical characteristics and outcomes, of people living with HIV diagnosed with ocular syphilis. RESULTS: Fifty-three people living with HIV were identified with ocular syphilis. Thirty-eight (71.6%) presented ocular symptoms. Twenty-three (43.3%) underwent lumbar puncture, 5 (9.4%) were positive for neurosyphilis. Forty-seven (88.6%) received treatment, 32 (68%) received standard treatment with aqueous crystalline penicillin G, and 15 (31.9%) were treated with alternative regimens due to the impossibility of hospitalization. Six (11.3%) individuals were lost to follow-up and/or did not receive treatment. Eighteen (56.2%) out of 32 individuals in the aqueous crystalline penicillin G group experienced serological response, 5 (15.6%) experienced treatment failure, and 9 (28.1%) were lost to follow-up. In the alternative therapy group, 12 out of 15 individuals (80%) experienced serological response. One (6.7%) experienced treatment failure, and 2 (13.3%) were lost to follow-up. CONCLUSIONS: During the COVID-19 health emergency in Mexico, alternative treatments for ocular syphilis demonstrated favorable clinical outcomes amid challenges in accessing hospitalization.

A rare case report of bilateral vestibulopathy due to otosyphilis.

RATIONALE: Bilateral vestibulopathy is an important cause of imbalance. There are multiple etiologies of bilateral vestibulopathy (BVP), but reports of BVP due to otosyphilis are rare. PATIENT CONCERNS: A 39-year-old male was referred to our medical center due to vertigo, persistent dizziness and gait disturbance for 2 months. DIAGNOSES: Bilateral vestibulopathy due to otosyphilis was considered in this case, as confirmed through analyses of vestibular function, laboratory tests, and penicillin treatment. INTERVENTIONS: The patient was was treated with a high dose of penicillin G (24 × 106 IU/d) for 14 days. OUTCOMES: The patient's symptoms had improved greatly following treatment, with dizziness and gait disturbance having completely resolved at 3 months following hospital discharge. LESSONS: Bilateral vestibulopathy should be considered when evaluating patients with acute or subacute persistent dizziness. Clinicians should also be aware of the potential for otosyphilis among patients who report BVP.

A sandwich-structured multifunctional platform based on self-assembled Ti3C2Tx@Au NPs films, antibiotics, and silent region SERS probe for the capture, determination, and drug resistance analysis of Gram-positive bacteria.

A multifunctional surface-enhanced Raman scattering (SERS) platform integrating sensitive detection and drug resistance analysis was developed for Gram-positive bacteria. The substrate was based on self-assembled Ti3C2Tx@Au NPs films and capture molecule phytic acid (IP6) to achieve specific capture of Gram-positive bacteria and different bacteria were analyzed by fingerprint signal. It had advantages of good stability and homogeneity (RSD = 8.88%). The detection limit (LOD) was 102 CFU/mL for Staphylococcus aureus and 103 CFU/mL for MRSA, respectively. A sandwich structure was formed on the capture substrate by signal labels prepared by antibiotics (penicillin G and vancomycin) and non-interference SERS probe molecules (4-mercaptobenzonitrile (2223 cm-1) and 2-amino-4-cyanopyridine (2240 cm-1)) to improve sensitivity. The LOD of Au NPs@4-MBN@PG to S. aureus and Au NPs@AMCP@Van to MRSA and S. aureus were all improved to 10 CFU/mL, with a wide dynamic linear range from 108 to 10 CFU/mL (R2 ≥ 0.992). The SERS platform can analyze the drug resistance of drug-resistant bacteria. Au NPs@4-MBN@PG was added to the substrate and captured MRSA to compare the SERS spectra of 4-MBN. The intensity inhomogeneity of 4-MBN at the same concentrations of MRSA and the nonlinearity at the different concentrations of MRSA revealed that MRSA was resistant to PG. Finally, the SERS platform achieved the determination of MRSA in blood. Therefore, this SERS platform has great significance for the determination and analysis of Gram-positive bacteria.

Antimicrobial Resistance Patterns in Patients with Vaginal Discharge: A 2019-2022 Analysis at the National Health Laboratory in Eritrea.

Background: Antimicrobial resistance poses a significant global threat to the treatment of bacterial infections, particularly in low- and middle-income regions such as Africa. This study is aimed at analyzing antimicrobial resistance patterns in vaginal swab samples from patients at the National Health Laboratory from 2019 to 2022. Methods: This retrospective study examined patient records from vaginal swab analyses performed at the National Health Laboratory between January 1, 2019, and December 31, 2022. Ethical approval was obtained from the Ministry of Health Research Ethical Approval and Clearance Committee on 15/02/2023. Results: Of the 622 samples, 83% underwent microbial isolation and identification. Citrobacter spp. exhibited high resistance (>43%) to antibiotics such as cephalexin, ceftazidime, nalidixic acid, ampicillin, gentamicin, and tetracycline. E. coli showed resistance rates of more than 50% to ampicillin, trimethoprim-sulfamethoxazole, and tetracycline. Klebsiella spp. and Proteus spp. exhibited resistance rates that exceeded 47% to specific antibiotics. Gram-positive bacteria have resistance rates of more than 49% with ampicillin, trimethoprim-sulfamethoxazole, tetracycline, oxacillin, vancomycin, and penicillin G. In particular, S. aureus demonstrated no resistance to rifampicin or clindamycin, while Streptococcus spp. showed 100% resistance to rifampicin and vancomycin. Several species, including Proteus species, Streptococcus spp., S. aureus, and Klebsiella spp. exhibited multidrug resistance. Conclusion: Most gram-negative bacteria displayed higher resistance of >45% to ampicillin, trimethoprim-sulfamethoxazole, and tetracycline. Among gram-positive bacteria, a higher resistance rate with ampicillin, trimethoprim-sulfamethoxazole, tetracycline, oxacillin, vancomycin, and penicillin G was recorded. S. aureus showed no resistance to rifampicin and clindamycin, and Strep. spp. indicated 100% resistance to rifampicin and vancomycin. This study highlights critical gaps and areas for further exploration. Expanding the spectrum of antibiotics tested and investigating underlying multidrug resistance mechanisms would provide a more comprehensive understanding of resistance patterns.

Neisseria meningitidis with decreased susceptibility to penicillin G and molecular characterization of the penA gene in strains isolated at University Hospital Centers of Casablanca and Marrakech (Morocco).

Introduction: the laboratory diagnosis of meningococcal meningitis relies on conventional techniques. This study aims to evaluate the correlation between the reduced sensitivity to penicillin G of Neisseria meningitidis (N.m) strains and the expression of the altered PBP 2 gene. Methods: out of 190 strains of N.m isolated between 2010 and 2021 at the bacteriology laboratories of Ibn Rochd University Hospital Centre (IR-UHC) in Casablanca and the UHC Mohammed VI in Marrakech, 23 isolates were part of our study. We first determined their state of sensitivity to penicillin G by E-Test strips and searched for the expression of the penA gene by PCR followed by Sanger sequencing. Results: of all the confirmed cases of N.m, 93.15% (n=177) are of serogroup B, 75.2% (n = 143) are sensitive to penicillin G and 24.73% (n = 47) are of intermediate sensitivity. No resistance to penicillin G was observed. Reduced sensitivity to penicillin G in N.m is characterized by mutations namely F504 L, A510 V, I515 V, G541 N and I566 V located in the C-terminal region of the penA gene encoding the penicillin-binding protein 2 (PBP2) (mosaic gene). Conclusion: our study presents useful data for the phenotypic and genotypic monitoring of resistance to penicillin G in N.m and can contribute to the analysis of genetic exchanges between different Neisseria species.

Trends of Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates Between 2012 and 2023: Results From an Open Italian Cohort.

BACKGROUND: Neisseria gonorrhoeae (Ng) is a public health priority because of the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance, and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), and ciprofloxacin (CIP) during a 10-year period. METHODS: We conducted a retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral, and pharyngeal samples at San Raffaele Scientific Institute, between September 2012 and February 2023. Minimum inhibitory concentrations of antibiotics were determined by gradient-test strips. Bivariate linear regression models were applied on logarithmic minimum inhibitory concentrations values; Cochran-Armitage test was used to determine a linear trend in the proportions of resistant strains. RESULTS: A total of 436 Ng isolates from 352 individuals were analyzed. Minimum inhibitory concentrations of CRO and PenG reduced over time ( P < 0.001, P = 0.030), AZM increased ( P = 0.001), and CIP and TET did not change ( P = 0.473, P = 0.272). The percentages of resistant strains were as follows: PenG, 89.9%; TET, 90.8%; CIP, 48.2%; AZM, and 4.4%. CRO-DS strains were 8.7%, and only 1 case of CRO-R was identified. The proportion of resistant strains increased over time for AZM ( P = 0.007), TET ( P = 0.001), and CIP ( P < 0.001), whereas it decreased for PenG ( P < 0.001) and CRO-DS/R strains ( P < 0.001). CONCLUSIONS: Ng strains showed high susceptibility to CRO, although we identified cases of DS/R and observed high levels of susceptibility to AZM. Overall, the recommended primary regimen for Ng treatment was confirmed to be effective.

Successful Antimicrobial Therapy of Esophageal Stenosis Because of Actinomycosis.

Esophageal stenosis can cause vomiting or dysphagia in children and is commonly treated with esophageal balloon dilation. However, surgery may be required if the stenosis does not respond to dilation. Although esophageal actinomycosis can cause severe esophageal strictures and be refractory to balloon dilation, it has been reported to respond effectively to antimicrobial therapy in adults. However, the course of the disease and appropriate treatment strategies in children are not well understood. We present a case of a previously healthy 2-year-old boy diagnosed with esophageal stenosis because of actinomycosis. The patient was treated with intravenous penicillin G, followed by oral amoxicillin for 8 weeks and 6 months, respectively. After completion of the antimicrobial treatment, the patient showed improvement in symptoms and endoscopic findings. At the 1-year follow-up, the patient showed consistent weight gain and normal growth without further intervention. This case highlights the importance of considering esophageal actinomycosis as a potential cause of esophageal stenosis in children and the potential effectiveness of antimicrobial therapy in avoiding surgical intervention.

A penicillinase-modified poly(N-isopropylacrylamide-co-acrylamide) smart hydrogel biosensor with superior recyclability for sensitive and colorimetric detection of penicillin G.

Antibiotics are widely used for treating bacterial infections. However, excessive or improper use of antibiotics can pose a serious threat to human health and water environments, and thus, developing cost-effective, portable and effective strategies to analyze and detect antibiotics is highly desired. Herein, we reported a responsive photonic hydrogel (RPH)-based optical biosensor (PPNAH) with superior recyclability for sensitive and colorimetric determination of a typical ß-lactam antibiotic penicillin G (PG) in water. This sensor was composed of poly(N-isopropylacrylamide-co-acrylamide) smart hydrogel with incorporated penicillinase and Fe3O4@SiO2 colloidal photonic crystals (CPCs). The sensor could translate PG concentration signals into changes in the diffraction wavelength and structural color of the hydrogel. It possessed high sensitivity and selectivity to PG and excellent detection performances for other two typical ß-lactam antibiotics. Most importantly, due to the unique thermosensitivity of the poly(N-isopropylacrylamide) moieties in the hydrogel, the PG-responded PPNAH sensor could be facilely regenerated via a simple physical method at least fifty times while without compromising its response performance. Besides, our sensor was suitable for monitoring the PG-contaminated environmental water and displayed satisfactory detection performances. Such a sensor possessed obvious advantages of superior recyclability, highly chemical stability, low production cost, easy fabrication, wide range of visual detection, simple and intuitive operation for PG detection, and environmental-friendliness, which holds great potential in sensitive and colorimetric detection of the PG residues in polluted water.

Selective adsorption and identification of penicillin G sodium in milk by molecularly imprinted polymer doped carbon dot.

A carbon dot (CD) was prepared by o-phenylenediamine and water, which showed bright yellow fluorescence under ultraviolet light irradiation (λ = 580 nm), and verified good fluorescence quenching effect on penicillin G sodium (Png-Na). Using methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a crosslinker, and Png-Na as a template, a kind of composite microsphere combining CD and molecularly imprinted polymer (MIP) was synthesized by surface-initiated atomic transfer radical polymerization (SI-ATRP). For reasons of comparison, we also prepared MIP without CD and non-imprinted polymers (NIPs). Through static and dynamic adsorption experiments, the maximum adsorption capacity was 47.05 mg g-1 and the equilibrium time was 30 min. High-performance liquid chromatography (HPLC) was utilized to determine the content of Png-Na in the spiked milk samples. A sensitive, rapid, and simple method for determination of Png-Na in food samples was developed. The utilized approach enabled the quantification of Png-Na within the concentration range 20-1000 µg L-1 (with a limit of detection of 5 µg L-1). The recoveries achieved were in the range 93.3-98.2%, with a relative standard deviation of 1.2-4.2%. The results demonstrated that CD@MIP possessed the capability of specific adsorption and fluorescence detection of Png-Na, enabling simultaneous detection and enrichment of Png-Na in real samples.

Evaluation of Antibiotic Penicillin G Activities Based on Electrochemical Measurement of a Tetrazolium Salt.

This study focused on the electrochemical properties of tetrazolium salts to develop a simple method for evaluating viable bacterial counts, which are indicators of drug susceptibility. Considering that the oxidized form of tetrazolium, which has excellent cell membrane permeability, changes to the insoluble reduced form formazan inside the cell, the number of viable cells was estimated based on the reduction current of the tetrazolium remaining in the bacterial suspension. Dissolved oxygen is an important component of bacterial activity. However, it interferes with the electrochemical response of tetrazolium. We estimated the number of viable bacteria in the suspension based on potential-selective current responses that were not affected by dissolved oxygen. Based on solubility, cell membrane permeability, and characteristic electrochemical properties of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium, we developed a method for rapidly measuring viable bacteria within one-fifth of the time required by conventional colorimetric methods for drug susceptibility testing.

Biodegradation of penicillin G sodium by Sphingobacterium sp. SQW1: Performance, degradation mechanism, and key enzymes.

Biodegradation is an efficient and cost-effective approach to remove residual penicillin G sodium (PGNa) from the environment. In this study, the effective PGNa-degrading strain SQW1 (Sphingobacterium sp.) was screened from contaminated soil using enrichment technique. The effects of critical operational parameters on PGNa degradation by strain SQW1 were systematically investigated, and these parameters were optimized by response surface methodology to maximize PGNa degradation. Comparative experiments found the extracellular enzyme to completely degrade PGNa within 60 min. Combined with whole genome sequencing of strain SQW1 and LC-MS analysis of degradation products, penicillin acylase and ß-lactamase were identified as critical enzymes for PGNa biodegradation. Moreover, three degradation pathways were postulated, including ß-lactam hydrolysis, penicillin acylase hydrolysis, decarboxylation, desulfurization, demethylation, oxidative dehydrogenation, hydroxyl reduction, and demethylation reactions. The toxicity of PGNa biodegradation intermediates was assessed using paper diffusion method, ECOSAR, and TEST software, which showed that the biodegradation products had low toxicity. This study is the first to describe PGNa-degrading bacteria and detailed degradation mechanisms, which will provide new insights into the PGNa biodegradation.

Early life exposure of infants to benzylpenicillin and gentamicin is associated with a persistent amplification of the gut resistome.

BACKGROUND: Infant gut microbiota is highly malleable, but the long-term longitudinal impact of antibiotic exposure in early life, together with the mode of delivery on infant gut microbiota and resistome, is not extensively studied. METHODS: Two hundred and eight samples from 45 infants collected from birth until 2 years of age over five time points (week 1, 4, 8, 24, year 2) were analysed. Based on shotgun metagenomics, the gut microbial composition and resistome profile were compared in the early life of infants divided into three groups: vaginal delivery/no-antibiotic in the first 4 days of life, C-section/no-antibiotic in the first 4 days of life, and C-section/antibiotic exposed in first 4 days of life. Gentamycin and benzylpenicillin were the most commonly administered antibiotics during this cohort's first week of life. RESULTS: Newborn gut microbial composition differed in all three groups, with higher diversity and stable composition seen at 2 years of age, compared to week 1. An increase in microbial diversity from week 1 to week 4 only in the C-section/antibiotic-exposed group reflects the effect of antibiotic use in the first 4 days of life, with a gradual increase thereafter. Overall, a relative abundance of Actinobacteria and Bacteroides was significantly higher in vaginal delivery/no-antibiotic while Proteobacteria was higher in C-section/antibiotic-exposed infants. Strains from species belonging to Bifidobacterium and Bacteroidetes were generally persistent colonisers, with Bifidobacterium breve and Bifidobacterium bifidum species being the major persistent colonisers in all three groups. Bacteroides persistence was dominant in the vaginal delivery/no-antibiotic group, with species Bacteroides ovatus and Phocaeicola vulgatus found to be persistent colonisers in the no-antibiotic groups. Most strains carrying antibiotic-resistance genes belonged to phyla Proteobacteria and Firmicutes, with the C-section/antibiotic-exposed group presenting a higher frequency of antibiotic-resistance genes (ARGs). CONCLUSION: These data show that antibiotic exposure has an immediate and persistent effect on the gut microbiome in early life. As such, the two antibiotics used in the study selected for strains (mainly Proteobacteria) which were multiple drug-resistant (MDR), presumably a reflection of their evolutionary lineage of historical exposures-leading to what can be an extensive and diverse resistome. Video Abstract.

Synthesis and Synergistic Antimicrobial Efficacy of Covalent Conjugates Composed of Epsilon-Poly-l-lysine and Beta-Lactam Antibiotics.

The increasing severity of problems posed by drug-resistant pathogens has compelled researchers to explore innovative approaches for infection prevention. Among these strategies, conjugation methods stand out for their convenience and high efficacy. In this study, multiple covalent conjugates were synthesized, incorporating the natural antimicrobial peptide epsilon-poly-l-lysine (EPL) and two commonly used ß-lactam antibiotics: penicillin G or ampicillin. Enhanced antimicrobial efficacy against typical Gram-negative pathogens, along with faster kill kinetics compared to combination approaches, was demonstrated by the EPL-Ampicillin covalent conjugates. Their antimicrobial mechanism was also substantiated through SEM and fluorescence tests in this work, confirming the inheritance of membrane-disrupting properties from EPL. Furthermore, the excellent biocompatibility of the raw materials was reserved in the covalent conjugates. This simplified conjugation method holds promise for the development of infection therapeutic drugs and potentially restores the sensitivity of conventional antibiotics to drug-resistant pathogens by introducing membrane-disrupting mechanisms.

A low-volume LC/MS method for highly sensitive monitoring of phenoxymethylpenicillin, benzylpenicillin, and probenecid in human serum.

Background: The optimization of antimicrobial dosing plays a crucial role in improving the likelihood of achieving therapeutic success while reducing the risks associated with toxicity and antimicrobial resistance. Probenecid has shown significant potential in enhancing the serum exposure of phenoxymethylpenicillin, thereby allowing for lower doses of phenoxymethylpenicillin to achieve similar pharmacokinetic/pharmacodynamic (PK/PD) targets. We developed a triple quadrupole liquid chromatography mass spectrometry (TQ LC/MS) analysis of, phenoxymethylpenicillin, benzylpenicillin and probenecid using benzylpenicillin-d7 and probenecid-d14 as IS in single low-volumes of human serum, with improved limit of quantification to support therapeutic drug monitoring. Methods: Sample clean-up was performed by protein precipitation using acetonitrile. Reverse phase chromatography was performed using TQ LC/MS. The mobile phase consisted of 55% methanol in water + 0.1% formic acid, with a flow rate of 0.4 mL min-1. Antibiotic stability was assessed at different temperatures. Results: Chromatographic separation was achieved within 2 minutes, allowing simultaneous measurement of phenoxymethylpenicillin, benzylpenicillin and probenecid in a single 15 µL blood sample. Validation indicated linearity over the range 0.0015-10 mg L-1, with accuracy of 96-102% and a LLOQ of 0.01 mg L-1. All drugs demonstrated good stability under different storage conditions. Conclusion: The developed method is simple, rapid, accurate and clinically applicable for the quantification of phenoxymethylpenicillin, benzylpenicillin and probenecid in tandem.

Enterococcal Infective Endocarditis - Post discharge treatment with continuous benzylpenicillin and ceftriaxone: A retrospective cohort study.

BACKGROUND: Enterococcal Infective Endocarditis (EIE) is usually treated with the combination of penicillin/ampicillin with gentamicin or ampicillin with ceftriaxone. To enable prolonged outpatient treatment, a combination of benzylpenicillin and ceftriaxone has been suggested. This study aimed to describe the incidence and characteristics of EIE and to determine the outcome of EIE cases treated with benzylpenicillin and ceftriaxone. METHODS: This was a retrospective single-center study including all patients diagnosed with infective endocarditis (IE) during 2016-2021, comparing EIE with IE caused by other pathogens. We described the outpatient treatment of patients with EIE, comparing those treated of benzylpenicillin - ceftriaxone with other regimes. RESULTS: Among 222 patients with IE, 44 (20%) were diagnosed with EIE. Those were older, had a male predominance (p = 0.035), and were more disabled (p = 0.004). The incidence of EIE reached 30% towards the last year, becoming the leading etiology. Twenty-six patients received outpatient treatment, five of whom were discharged with benzylpenicillin and ceftriaxone. Adding patients from this cohort to the scarce data available, revealed similar recurrence and mortality rates compared to other treatment regimes. CONCLUSIONS: EIE is becoming a more frequent cause of IE, involving older, more disabled patients with male predominance. Our experience and existing literature suggest that the combination of benzylpenicillin and ceftriaxone is as safe as more conventional regimes, although further research is needed.

Rising Incidence of Syphilitic Uveitis-Related Hospitalizations in the US.

Importance: The number of syphilis cases continues to increase in the US every year since 2001 with a 74% increase observed since 2017. In addition, there remains a national shortage of injectable penicillin G. Despite the increase in reported cases, to the authors' knowledge, there has been no recent nationwide study investigating the trends in incidence of syphilitic uveitis. Objective: To evaluate the national and regional incidence of syphilitic uveitis-related hospitalizations in the US. Design, Setting, and Participants: This was a retrospective, cross-sectional study. The Nationwide Inpatient Sample was queried to identify all inpatient admissions with a diagnosis of syphilitic uveitis in the US between the years 2010 and 2019. Analyses were performed to determine baseline sociodemographic characteristics and identify national and regional trends in incidence. All patients hospitalized with a diagnosis of syphilis, uveitis, and/or syphilitic uveitis were eligible for inclusion. Statistical analysis of study data took place in June 2023. Exposure: Diagnosis of syphilis, uveitis, and/or syphilitic uveitis on inpatient admissions during the years 2010 to 2019 in the Nationwide Inpatient Sample. Main Outcome Measures: The primary outcome was to determine trends in the national and regional incidence of syphilitic uveitis-related hospitalizations in the US. Secondary outcome measures included sociodemographic characteristics of patients with syphilitic uveitis, incidence stratified by sex and race and ethnicity, and median charge per syphilitic uveitis hospital admission. Results: From the Nationwide Inpatient Sample, inpatient data from 444 674 patients (median [IQR] age, 53 [37-67] years; 54.8% male) were analyzed. There were an estimated 5581 syphilitic uveitis-related hospitalizations during the 10-year study period. The median (IQR) age of individuals with syphilitic uveitis was 45 (35-55) years, and 4395 patients (78.9%) were male. Syphilitic uveitis disproportionately affected African American individuals (1787 patients [32%], although they compose 13.6% of the population) and those belonging to the lowest median household income quartile (2163 [38.8%]). The national incidence was 0.15 per 100 000 population and showed an increasing trend over the years, with the lowest incidence in 2011 (0.08 per 100 000 population) and the highest incidence in 2019 (0.23 per 100 000 population; P = .04). Regional analysis showed an increase in incidence across all 4 US geographical regions. A total of 1293 patients (23.2%) had comorbid AIDS. Conclusion and Relevance: Although this cross-sectional study only captured inpatient diagnosis, an increasing incidence of syphilitic uveitis-related hospitalizations was observed in the US between 2010 and 2019. Given the concomitant national shortage of injectable penicillin G, results suggest that clinicians should maintain a high index of suspicion for syphilis when evaluating patients with intraocular inflammation.

[Clinical and etiological characteristics of infectious vulvovaginitis in children in Zhejiang province from 2009 to 2019].

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced ß-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.