A Case Report of Black Hairy Tongue (Melanotrichia Linguae or Lingua Pilosa Nigra).

Black hairy tongue is a benign condition that can be associated with several varying causes. Its etiology is often linked with fungal infection and adverse reactions to various drugs. We present a case of an adult patient who developed a black hairy tongue while on ceftriaxone and pantoprazole for 10 days. The fungus on his tongue was not identified as the causative agent, and recovery was achieved by changing his medications. Ceftriaxone was replaced with trimethoprim/sulfamethoxazole 5 mg/kg intravenous, and pantoprazole was fully stopped. The black lesion on the tongue was observed to regress over several days. Clinicians should be aware of this particular side effect of certain antibiotics.

Clinical characteristic, management, and outcomes of cervical spinal brucellosis: a retrospective cohort study over 1-year postoperative follow-up.

BACKGROUND: The incidence of cervical spinal brucellosis is low, only a few case reports have been published, and case series are not widely reported in the medical literature. Therefore, clinical features, management, and outcomes of cervical spinal brucellosis are relatively unknown. In this series, the authors report 15 cases of patients with cervical spinal brucellosis, including clinical characteristic, imaging findings, management plans, the institution's experience, and outcomes at 1 year postoperatively. METHODS: The study reviewed the clinical and radiographic records of 15 patients who received antimicrobial pharmacotherapy, and anterior cervical debridement and fusion for cervical spinal brucellosis. The data collected included patient demographic characteristics, spinal level affected, abscess, neurology, pathological reports, duration and type of antimicrobial regimens, details of orthopedic management, and complications incurred during the procedure. RESULTS: Neck pain (100%) and limb paralysis (86.7%) were the most common clinical presentations, and the disease had a rapid progression. The C6-7 segment was the most commonly affected segment, followed by C4-5 and C5-6. Imaging commonly revealed epidural or paravertebral abscesses (80%). There was a significant improvement in the VAS, JOA, and NDI scores three months after surgery, and the scores continued to improve until the final follow-up. There was a statistically significant difference between the pre- and postoperative scores (P < 0.05). The ESR and CRP levels returned to normal within three months postoperatively, being 7.7 ± 4.5 mm/h and 7.55 ± 3.48 mg/L, respectively. There were statistically significant differences between the pre- and postoperative levels (P < 0.05). The positive rate of bacterial culture testing of pus or lesion tissues was only 40%, but blood cultures revealed an even lower positivity rate (33.3%). The average antimicrobial pharmacotherapy regimen duration was 6.1 ± 1.9 months. All patients achieved intervertebral bone fusion within 8 months (4.8 ± 1.4 months) after surgery and were cured with non-recurrence. CONCLUSIONS: Spinal brucellosis rarely affects the cervical region, but its impact is more dangerous due to potential complications such as paraplegia or tetraplegia arising from epidural abscesses that compress the spinal cord. Surgical debridement, along with essential antimicrobial therapy, is an effective strategy and can lead to satisfactory prognosis in managing cervical spinal brucellosis.

Lowering mortality risk in CR-HvKP infection in intestinal immunohistological and microbiota restoration.

Gut damage during carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-HvKP) infection is associated with a death risk. Understanding the mechanisms by which CR-HvKP causes intestinal damage and gut microbiota alteration, and the impact on immunity, is crucial for developing therapeutic strategies. This study investigated if gastrointestinal tract damage and disruption of gut microbiota induced by CR-HvKP infection undermined host immunity and facilitated multi-organ invasion of CR-HvKP; whether the therapeutic value of the rifampicin (RIF) and zidovudine (ZDV) combination was attributed to their ability to repair damages and restore host immunity was determined. A sepsis model was utilized to assess the intestinal pathological changes. Metagenomic analysis was performed to characterize the alteration of gut microbiota. The effects of the RIF and ZDV on suppressing inflammatory responses and improving immune functions and gut microbiota were evaluated by immunopathological and transcriptomic analyses. Rapid colonic damage occurred upon activation of the inflammation signaling pathways during lethal infections. Gut inflammation compromised host innate immunity and led to a significant decrease in probiotics abundance, including Bifidobacterium and Lactobacillus. Treatment with combination drugs significantly attenuated the inflammatory response, up-regulated immune cell differentiation signaling pathways, and promoted the abundance of Bifidobacterium (33.40 %). Consistently, supplementation of Bifidobacterium alone delayed the death in sepsis model. Gut inflammation and disrupted microbiota are key disease features of CR-HvKP infection but can be reversed by the RIF and ZDV drug combination. The finding that these drugs can restore host immunity through multiple mechanisms is novel and deserves further investigation of their clinical application potential.

Evaluation of the Economic Impact of Streptococcus suis-Associated Disease.

The economic impact of Streptococcus suis-associated disease at farm level is well known by the producers, but the cost in a region or a country is more difficult to evaluate due to the lack of a centralized data system, the different incidences, and the control measures applied by each producer. In this chapter, we describe a method based on the information gathered through interviews with veterinary practitioners. A comprehensive questionnaire created specifically for the disease can help to conduct the interviews. The questions include information about the proportions of farms, batches and animals clinically affected, mortality, metaphylactic and therapeutic treatments, use of vaccines, and proportion of cases that are diagnosed at the laboratory. As the questionnaire is quite complex, the best option to obtain the data is send the questionnaire to the selected veterinarians to allow them to collect some data and make an interview with them some days later. The information allows to estimate the costs due to mortality, antimicrobial treatments, the use of autogenous vaccines, and analyses performed. Initially they are calculated per animal in each affected production phase, and later it can be extrapolated to estimate the annual cost per affected production unit and per country. The model does not consider indirect costs such as the cost as a zoonosis, the revenues forgone, or an increase of labor.

Antibiofilm Activity of Combretum micranthum G. Don Catechin-Sugar Phytocomplex on Pseudomonas aeruginosa.

Clinicians often have to face infections caused by microorganisms that are difficult to eradicate due to their resistance and/or tolerance to antimicrobials. Among these pathogens, Pseudomonas aeruginosa causes chronic infections due to its ability to form biofilms on medical devices, skin wounds, ulcers and the lungs of patients with Cystic Fibrosis. In this scenario, the plant world represents an important reservoir of natural compounds with antimicrobial and/or antibiofilm properties. In this study, an extract from the leaves of Combretum micranthum G. Don, named Cm4-p, which was previously investigated for its antimicrobial activities, was assayed for its capacity to inhibit biofilm formation and/or to eradicate formed biofilms. The model strain P. aeruginosa PAO1 and its isogenic biofilm hyperproducer derivative B13 were treated with Cm4-p. Preliminary IR, UV-vis, NMR, and mass spectrometry analyses showed that the extract was mainly composed of catechins bearing different sugar moieties. The phytocomplex (3 g/L) inhibited the biofilm formation of both the PAO1 and B13 strains in a significant manner. In light of the obtained results, Cm4-p deserves deeper investigations of its potential in the antimicrobial field.

Home nursing and self-administered outpatient parenteral antimicrobial treatment: a comparison of demographics and outcomes from a large regional hospital in Queensland, Australia.

BACKGROUND: Outpatient parenteral antimicrobial treatment (OPAT) is a safe and effective therapy used in several settings across Australia. As OPAT services expand their inclusion criteria to include complex patient populations, there is an increased need for selecting appropriate patients to receive either healthcare-administered OPAT (H-OPAT) or self-administered OPAT (S-OPAT). AIMS: To describe patient demographics, diagnosis, microbiology and outcomes of patients treated by H-OPAT and S-OPAT within the Sunshine Coast Hospital and Health Service, Australia. METHODS: Data on demographics, diagnoses, treatment and outcomes on all patients treated by H-OPAT and S-OPAT from March 2017 to December 2019 were collected retrospectively. RESULTS: One hundred and sixty-five patients (62.26%) were enrolled in H-OPAT and 100 patients (37.74%) in S-OPAT. S-OPAT patients were significantly younger. H-OPAT patients were more comorbid. Bone and joint infections were the most treated infections and were more likely to be treated by S-OPAT. There was no difference in treatment duration, cure and complication rates between S-OPAT and H-OPAT. Longer duration of therapy was associated with more complications. Treatment failure was associated with infections due to multiple organisms, number of comorbidities and treatment of surgical site, skin and soft tissue infections. CONCLUSIONS: There were significant differences in demographics between H-OPAT and S-OPAT without any difference in outcomes. Overall failure and complication rates were low. Higher rates of treatment failure were predicted by the diagnosis, number of comorbidities and number of organisms treated.

Meningococcal meningitis in Spain in the Horizon 2030: A position paper.

Meningococcal meningitis (MM) and invasive meningococcal disease remain a major public health problem that generates enormous public alarm. It is caused by Neisseria meningitidis, a Gram-negative diplococcus with an enormous capacity for acute and rapidly progressive disease, both episodic and epidemic in nature, with early diagnosis and treatment playing a major role. It occurs at any age, but is most common in children under 5 years of age followed by adolescents. Although most cases occur in healthy people, the incidence is higher in certain risk groups. Despite advances in reducing the incidence, it is estimated that in 2017 there were around 5 million new cases of MM worldwide, causing approximately 290,000 deaths and a cumulative loss of about 20,000,000 years of healthy life. In Spain, in the 2021/22 season, 108 microbiologically confirmed cases of MM were reported, corresponding to an incidence rate of 0.23 cases per 100,000 inhabitants. This is a curable and, above all, vaccine-preventable disease, for which the World Health Organisation has drawn up a roadmap with the aim of reducing mortality and sequelae by 2030. For all these reasons, the Illustrious Official College of Physicians of Madrid (ICOMEM) and the Medical Associations of 8 other provinces of Spain, have prepared this opinion document on the situation of MM in Spain and the resources and preparation for the fight against it in our country. The COVID-19 and Emerging Pathogens Committee of ICOMEM has invited experts in the field to participate in the elaboration of this document.

Antimicrobial treatment in invasive infections caused by Gordonia bronchialis: systematic review.

Background: Corynebacterium, Nocardia, Rhodococcus, Mycobacterium, as well as Gordonia genera belongs to the genus Gordonia, Actinomycetia class. Gordonia bronchialis is a nitrate-reducing, urease-producing, non-motile, force aerobe with a rod-like figure that is known to arrangement into sessile, cord-like groups. This systematic review aimed to establish whether and what invasive infections in humans were caused by Gordonia bronchialis, and to evaluate outcomes of administered antibiotic treatment. Methods: We have registered this systematic review in PROSPERO database of systematic reviews and meta-analyses with the number CRD42022369974. Results: A total of 24 publications were included (22 case reports and two case series) with 28 individual cases. The oldest patients had 92 years, and the youngest patients had 13 years. Clinical signs of infection were present in six patients (21%). All isolates were susceptible to ciprofloxacin, imipenem, and amikacin. Vancomycin was the most frequently used antibiotic with nine cases followed by ciprofloxacin, ceftriaxone, and amoxicillin/clavulanic acid. Conclusion: Although there are no standardized recommendations to date, successful treatment with a favorable outcome has most often been carried out with fluoroquinolones, vancomycin with or without aminoglycosides, as well as carbapenems.

Antimicrobial Treatment Challenges in the Management of Infective Spondylodiscitis Associated with Hemodialysis: A Comprehensive Review of Literature and Case Series Analysis.

Infective spondylodiscitis (ISD), the infection of vertebral bodies and surrounding tissues, is a rare complication with major impact on the long-term survival of hemodialysis (HD) patients. Although the most frequent etiology is staphylococcal, identifying these pathogens in blood cultures and biopsy cultures is often difficult. This paper aims to present suitable antibiotic combinations for the treatment of these patients, which is usually challenging in the case of an unidentified pathogen. We presented the therapies applied for 13 HD patients and 19 patients without chronic kidney disease (CKD), diagnosed with ISD between 2013 and 2023 in Bihor County. The percentage of positive blood cultures was low in both groups (30.78% HD vs. 15.78% non-HD). The average length of antibiotic therapy was 5.15 weeks in HD patients and 6.29 weeks in non-HD patients. The use of Carbapenem alone (e.g., Meropenem) for an average of 19.6 days for patients in HD when the pathogen was not identified has proven to be efficient in most cases, similarly to using Vancomycin and Fluoroquinolone/Cephalosporines in combination. Regarding the non-CKD patients, the use of Clindamycin in various combinations for an average of 30.3 days has proven to be efficient in more than 90% of cases of ISD with a nonidentified pathogen. Within 2 years after ISD was diagnosed, 12 of the 13 HD patients passed away, mainly due to cardiovascular causes. Unfortunately, there are no guidelines in the literature concerning the empiric treatment of ISD in the particular case of HD patients. Upon checking the literature on PubMed and Google Scholar, only 10 studies provided relevant data regarding ISD treatment for HD patients. More data about the treatment and evolution of these patients is needed in order to elaborate a truly relevant metanalysis.

In vitro effects of phytogenic feed additive on Piscirickettsia salmonis growth and biofilm formation.

Piscirickettsiosis is the main cause of mortality in salmonids of commercial importance in Chile, which is caused by Piscirickettsia salmonis, a Gram-negative, γ-proteobacteria that can produce biofilm as one of its virulence factors. The Chilean salmon industry uses large amounts of antibiotics to control piscirickettsiosis outbreaks, which has raised concern about its environmental impact and the potential to induce antibiotic resistance. Thus, the use of phytogenic feed additives (PFA) with antibacterial activity emerges as an interesting alternative to antimicrobials. Our study describes the antimicrobial action of an Andrographis paniculate-extracted PFA on P. salmonis planktonic growth and biofilm formation. We observed complete inhibition of planktonic and biofilm growth with 500 and 400 µg/mL of PFA for P. salmonis LF-89 and EM-90-like strains, respectively. Furthermore, 500 µg/mL of PFA was bactericidal for both evaluated bacterial strains. Sub-inhibitory doses of PFA increase the transcript levels of stress (groEL), biofilm (pslD), and efflux pump (acrB) genes for both P. salmonis strains in planktonic and sessile conditions. In conclusion, our results demonstrate the antibacterial effect of PFA against P. salmonis in vitro, highlighting the potential of PFA as an alternative to control Piscirickettsiosis.

Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021.

BACKGROUND: Tularemia, a potentially fatal zoonosis caused by Francisella tularensis, has been reported from nearly all US states. Information on relative effectiveness of various antimicrobials for treatment of tularemia is limited, particularly for newer classes such as fluoroquinolones. METHODS: Data on clinical manifestations, antimicrobial treatment, and illness outcome of patients with tularemia are provided voluntarily through case report forms to the US Centers for Disease Control and Prevention by state and local health departments. We summarized available demographic and clinical information submitted during 2006-2021 and evaluated survival according to antimicrobial treatment. We grouped administered antimicrobials into those considered effective for treatment of tularemia (aminoglycosides, fluoroquinolones, and tetracyclines) and those with limited efficacy. Logistic regression models with a bias-reduced estimation method were used to evaluate associations between antimicrobial treatment and survival. RESULTS: Case report forms were available for 1163 US patients with tularemia. Francisella tularensis was cultured from a clinical specimen (eg, blood, pleural fluid) in approximately half of patients (592; 50.9%). Nearly three-quarters (853; 73.3%) of patients were treated with a high-efficacy antimicrobial. A total of 27 patients (2.3%) died. After controlling for positive culture as a proxy for illness severity, use of aminoglycosides, fluoroquinolones, and tetracyclines was independently associated with increased odds of survival. CONCLUSIONS: Most US patients with tularemia received high-efficacy antimicrobials; their use was associated with improved odds of survival regardless of antimicrobial class. Our findings provide supportive evidence that fluoroquinolones are an effective option for treatment of tularemia.

Incidence and Management of Hardware-Related Wound Infections in Spinal Cord, Peripheral Nerve Field, and Deep Brain Stimulation Surgery: A Single-Center Study.

INTRODUCTION: Neuromodulation using deep brain stimulation (DBS), spinal cord stimulation (SCS), and peripheral nerve field stimulation (PNFS) to treat neurological, psychiatric, and pain disorders is a rapidly growing field. Infections related to the implanted hardware are among the most common complications and result in health-related and economic burden. Unfortunately, conservative medical therapy is less likely to be successful. In this retrospective study, we aimed to identify characteristics of the infections and investigated surgical and antimicrobial treatments. METHODS: A retrospective analysis was performed of patients with an infection related to DBS, SCS, and/or PNFS hardware over an 8-year period at our institution. Data were analyzed for type of neurostimulator, time of onset of infection following the neurosurgical procedure, location, and surgical treatment strategy. Surgical treatment of infections consisted of either a surgical wound revision without hardware removal or a surgical wound revision with partial or complete hardware removal. Data were further analyzed for the microorganisms involved, antimicrobial treatment and its duration, and clinical outcome. RESULTS: Over an 8-year period, a total of 1,250 DBS, 1,835 SCS, and 731 PNFS surgeries were performed including de novo system implantations, implanted pulse generator (IPG) replacements, and revisions. We identified 82 patients with infections related to the neurostimulator hardware, representing an incidence of 3.09% of the procedures. Seventy-one percent of the patients had undergone multiple surgeries related to the neurostimulator prior to the infection. The infections occurred after a mean of 12.2 months after the initial surgery. The site of infection was most commonly around the IPG, especially in DBS and SCS. The majority (62.2%) was treated by surgical wound revision with simultaneous partial or complete removal of hardware. Microbiological specimens predominantly yielded Staphylococcus epidermidis (39.0%) and Staphylococcus aureus (35.4%). After surgery, antimicrobials were given for a mean of 3.4 weeks. The antimicrobial regime was significantly shorter in patients with hardware removal in comparison to those who only had undergone surgical wound revision. One intracranial abscess occurred. No cases of infection-related death, sepsis, bacteremia, or intraspinal abscesses were found. CONCLUSION: Our data did show the predominance of S. epidermidis and S. aureus as etiologic organisms in hardware-related infections. Infections associated with S. aureus most likely required (partial) hardware removal. Aggressive surgical treatment including hardware removal shortens the duration of antimicrobial treatment. Clear strategies should be developed to treat hardware-related infections to optimize patient management and reduce health- and economic-related burden.

Clinical practice recommendations for infectious disease management of diabetic foot infection (DFI) - 2023 SPILF.

In march 2020, the International Working Group on the Diabetic Foot (IWGDF) published an update of the 2015 guidelines on the diagnosis and management of diabetic foot infection (DFI). While we (the French ID society, SPILF) endorsed some of these recommendations, we wanted to update our own 2006 guidelines and specifically provide informative elements on modalities of microbiological diagnosis and antibiotic treatment (especially first- and second-line regiments, oral switch and duration). The recommendations put forward in the present guidelines are addressed to healthcare professionals managing patients with DFI and more specifically focused on infectious disease management of this type of infection, which clearly needs a multidisciplinary approach. Staging of the severity of the infection is mandatory using the classification drawn up by the IWGDF. Microbiological samples should be taken only in the event of clinical signs suggesting infection in accordance with a strict preliminarily established protocol. Empirical antibiotic therapy should be chosen according to the IWGDF grade of infection and duration of the wound, but must always cover methicillin-sensitive Staphylococcus aureus. Early reevaluation of the patient is a fundamental step, and duration of antibiotic therapy can be shortened in many situations. When osteomyelitis is suspected, standard foot radiograph is the first-line imagery examination and a bone biopsy should be performed for microbiological documentation. Histological analysis of the bone sample is no longer recommended. High dosages of antibiotics are recommended in cases of confirmed osteomyelitis.

Antibiotic use and outcome in patients with negative blood cultures, a new target population for antimicrobial stewardship interventions: A prospective multicentre cohort (NO-BACT).

OBJECTIVES: To evaluate the appropriateness of antimicrobial treatment and the risk factors for mortality in patients with negative blood cultures (BC), in order to evaluate whether this population would be a suitable target for antimicrobial stewardship (AMS) interventions. METHODS: A multicentre prospective cohort study of patients with negative BC in three Spanish hospitals between October 2018 and July 2019 was performed. The main endpoints were the appropriateness of antimicrobial treatment (evaluated by two investigators according to local guidelines) and 30-day mortality. Cox-regression was performed to estimate the association between variables and 30-day mortality. RESULTS: Of 1011 patients in whom BC was obtained, these were negative in 803 (79%) and were included; 30-day mortality was 9% (70 patients); antibiotic treatment was considered inappropriate in 299 (40%) of 747 patients evaluated at day 2, and in 266 (46%) of 573 at day 5-7. The variables independently associated with increased risk of 30-day mortality were higher age (HR 1.05; 95% CI 1.03-1.07), neoplasia (HR 2.73; 95% CI 1.64-4.56), antibiotic treatment in the 48 h prior to BC extraction (HR 2.06; 95% CI 1.23-3.43) and insufficient antibiotic coverage at day 2 after BC obtainment (HR 2.35; 95% CI 1.39-4.00). Urinary, catheter and biliary sources of infection were associated with lower risk (HR 0.40; 95% CI 0.20-0.81). CONCLUSIONS: Antimicrobial treatment is frequently inappropriate among patients with negative BC; insufficient antibiotic coverage at day 2 was associated with mortality. These results suggest that patients with negative BC are a suitable population for AS interventions. SUMMARY: Antimicrobial treatment in patients with negative blood culture was frequently inappropriate, and inappropriate coverage at day 2 was associated with increased risk of death. These data support the consideration of this population as a potential target for antimicrobial stewardship interventions.

Lack of microbiological awareness on the ward as a key factor for inappropriate use of anti-infectives: results of a point prevalence study and user satisfaction survey in a large university hospital in Austria.

PURPOSE: Although diagnostic stewardship issues in clinical microbiology harbor an optimization potential for anti-infective consumption, they are only marginally addressed in antimicrobial stewardship (AMS) programs. As part of an AMS point prevalence (PPS) survey we therefore aimed to gain a more dynamic view on the microbiological awareness within therapeutic regimens. By examining whether initial microbiological sampling was performed and in which way microbiological results were incorporated into further treatment considerations we sought to find out to what extent these points determine the appropriateness of treatment regimens. METHODS: PPS was performed at the University Hospital Salzburg (1524 beds) in May 2021. Relevant data was determined from the patient charts and the appropriateness of anti-infective use was assessed using predefined quality indicators. Six months after the PPS, a questionnaire was administered to clinicians to obtain information on the use of microbiological findings and their relevance in the clinic. RESULTS: Lack of microbiological awareness in the clinical setting proved to be the key reason for an overall inadequate use of anti-infectives (35.4% of cases rated as inadequate), ahead of the aspects of dose (24.1%), empirical therapy (20.3%) and treatment duration (20.2%). This was particularly the case for broad-acting agents and was most evident in urinary tract infections, skin and soft tissue infections, and pneumonia. The results of the questionnaire indicate a discrepancy between the physicians surveyed and the routine clinical setting. CONCLUSION: A high potential in improving the use of anti-infectives in hospitals seems to lie in a strong emphasis on microbiological diagnostic stewardship measures.

Pharmacodynamics of zoliflodacin plus doxycycline combination therapy against Neisseria gonorrhoeae in a gonococcal hollow-fiber infection model.

Antimicrobial resistance in the sexually transmitted bacterium Neisseria gonorrhoeae is compromising the management and control of gonorrhea globally. Optimized use and enhanced stewardship of current antimicrobials and development of novel antimicrobials are imperative. The first in class zoliflodacin (spiropyrimidinetrione, DNA Gyrase B inhibitor) is a promising novel antimicrobial in late-stage clinical development for gonorrhea treatment, i.e., the phase III randomized controlled clinical trial (ClinicalTrials.gov Identifier: NCT03959527) was recently finalized, and zoliflodacin showed non-inferiority compared to the recommended ceftriaxone plus azithromycin dual therapy. Doxycycline, the first-line treatment for chlamydia and empiric treatment for non-gonococcal urethritis, will be frequently given together with zoliflodacin because gonorrhea and chlamydia coinfections are common. In a previous static in vitro study, it was indicated that doxycycline/tetracycline inhibited the gonococcal killing of zoliflodacin in 6-h time-kill curve analysis. In this study, our dynamic in vitro hollow-fiber infection model (HFIM) was used to investigate combination therapies with zoliflodacin and doxycycline. Dose-range experiments using the three gonococcal strains WHO F (susceptible to relevant therapeutic antimicrobials), WHO X (extensively drug-resistant, including ceftriaxone-resistant; zoliflodacin-susceptible), and SE600/18 (zoliflodacin-susceptible strain with GyrB S467N substitution) were conducted simulating combination therapy with a single oral dose of zoliflodacin 0.5-4 g combined with a doxycycline daily oral dose of 200 mg administered as 100 mg twice a day, for 7 days (standard dose for chlamydia treatment). Comparing combination therapy of zoliflodacin (0.5-4 g single dose) plus doxycycline (200 mg divided into 100 mg twice a day orally, for 7 days) to zoliflodacin monotherapy (0.5-4 g single dose) showed that combination therapy was slightly more effective than monotherapy in the killing of N. gonorrhoeae and suppressing emergence of zoliflodacin resistance. Accordingly, WHO F was eradicated by only 0.5 g single dose of zoliflodacin in combination with doxycycline, and WHO X and SE600/18 were both eradicated by a 2 g single dose of zoliflodacin in combination with doxycycline; no zoliflodacin-resistant populations occurred during the 7-day experiment when using this zoliflodacin dose. When using suboptimal (0.5-1 g) zoliflodacin doses together with doxycycline, gonococcal mutants with increased zoliflodacin MICs, due to GyrB D429N and the novel GyrB T472P, emerged, but both the mutants had an impaired biofitness. The present study shows the high efficacy of zoliflodacin plus doxycycline combination therapy using a dynamic HFIM that more accurately and comprehensively simulate gonococcal infection and their treatment, i.e., compared to static in vitro models, such as short-time checkerboard experiments or time-kill curve analysis. Based on our dynamic in vitro HFIM work, zoliflodacin plus doxycycline for the treatment of both gonorrhea and chlamydia can be an effective combination.

Potential delayed and/or missed STI diagnoses among outpatients presenting with lower genitourinary tract symptoms: a real-world database study.

OBJECTIVES: Sexually transmitted infection (STI) diagnosis is complicated as these infections can present with lower genitourinary tract symptoms (LGUTS) that overlap with other disorders, i.e. urinary tract infections (UTIs). The study's objective was to determine potential missed STI diagnoses from patients presenting with LGUTS in the US between January 2010 and December 2019. METHODS: The de-identified insurance claims data from the IBM® MarketScan® Research Databases were collected from patients (14-64 years old) who presented with LGUTS, which could be caused by an STI. A 'GAP' cohort was created, consisting of episodes with potentially delayed STI (Chlamydia trachomatis [CT]/Neisseria gonorrhoeae [NG]) treatment. The intention was to capture episodes where an STI was not initially suspected. Four subgroups were defined depending on the treatment received (fluoroquinolone; azithromycin and/or doxycycline; cephalosporins; gentamicin and azithromycin). RESULTS: The GAP cohort consisted of 833,574 LGUTS episodes from the original cohort (23,537,812 episodes). Post-index CT/NG testing was carried out for 4.6% and 5.4% of the episodes from men and women, respectively. There were ≥2 return visits for 16.1% and 15.8% of the episodes from men and women, respectively. A substantial percentage of episodes from men (52.1%) and women (68.3%) were diagnosed with a UTI and/or acute cystitis at the index prior to receiving post-index STI treatment. Other top conditions diagnosed at index for men were dysuria (25.8% of the episodes), orchitis/epididymitis (14.3% of the episodes), and acute prostatitis (10.1% of the episodes), and for women were dysuria (24.2% of the episodes), vaginitis/vulvitis/vulvovaginitis (11.7% of the episodes), and cervicitis (3.3% of the episodes). CONCLUSION: These findings highlight delayed STI antibiotic treatment and low rates of CT/NG testing, suggesting late STI consideration and suboptimal diagnosis. Additionally, our study illustrates the importance of accurately diagnosing and treating STIs in patients with LGUTS and associated conditions, to avoid antibiotic misuse and complications from delayed administration of appropriate treatment.

Synergistic Strategies of Heat and Peroxyacetic Acid Disinfection Treatments for Salmonella Control.

The food industry has recognized a pressing need for highly effective disinfection protocols to decrease the risk of pathogen emergence and proliferation in food products. The integration of antimicrobial treatments in food production has occurred as a potential strategy to attain food items of superior quality with respect to microbiological safety and sensory attributes. This study aims to investigate the individual and synergistic effects of heat and peroxyacetic acid on the inactivation of bacterial cells, considering various contact times and environmental conditions. Four Salmonella serotypes, isolated from industrial meat production surfaces, were employed as model organisms. By systematically assessing the impacts of individual factors and synergistic outcomes, the effectiveness of bacterial cell inactivation and the efficiency of heat and peroxyacetic acid could be predicted. To better approximate real-world food processing conditions, this study also incorporated a bovine albumin-rich condition as a simulation of the presence of organic loads in processing steps. The findings revealed the essential need for a synergistic interplay of investigated parameters with the following optimized values: 1.5% concentration of peroxyacetic acid, temperature range of 60-65 °C, and contact time of 3 min for the complete effect regardless of the degree of contamination.