Oral Linezolid Research Articles

P-1378. Linezolid For Early Syphilis Treatment: Pilot study

Abstract Background Syphilis rates have been increasing. At the same time, important shortages of benzathine penicillin G have been reported. Existing alternatives, doxycycline, tetracycline, and azithromycin are inadequate to treat syphilis in all patients due to the absence of safety data in pregnancy and children, or antibiotic resistance, respectively. Linezolid is an FDA-approved, safe, low-cost, oral antibiotic that crosses the blood-brain barrier. It has shown efficacy against Treponema pallidum in vitro and in animal studies. Although a recent clinical study evaluating of 600mg Linezolid once daily for 5 days showed limited success, pharmacological simulations show that a longer regimen may be efficacious. We aimed to assess the efficacy of linezolid 600mg, twice a day for 10 days for the treatment of early syphilis. Methods We are conducting a randomized, non-comparative, pilot study enrolling 24 adult patients (18 linezolid, 6 penicillin) with primary, secondary, or early latent syphilis in Chicago, Illinois, and Jackson, Mississippi. The experimental arm receives oral linezolid 600mg twice daily for ten days, while the control arm receives benzathine penicillin G 2.4 million units intramuscularly once. The main outcome is a ≥4-fold RPR titer decline by 6 months after treatment. Linezolid participants are monitored for adherence and adverse events during treatment. Clinical and serological response is evaluated at 1-, 3-, and 6-month follow-up visits. Results Currently, six out of 24 participants are enrolled in the study; four in the linezolid arm, and two in the penicillin arm. All participants had early latent syphilis. All participants receiving linezolid adhered 100%. One penicillin participant (enrollment RPR 1:16, 3-month RPR 1:2) and one linezolid participant (enrollment RPR 1:64, 3-month RPR 1:16) have completed their 3-month follow-up. No serious adverse reactions have been reported. Conclusion Studies of new treatment options for syphilis are underway Disclosures Jeffrey Klausner, MD MPH, Direct Diagnostics: Advisor/Consultant

Three Strikes

Abstract A 56-year-old female patient presented with severe abdominal pain and intra-abdominal/retroperitoneal fluid collections growing Escherichia coli and vancomycin-resistant Enterococcus faecium; oral linezolid and cefdinir were prescibed. Pancreatic enzymes, lactate, serum chemistry studies, and blood glucose were unremarkable during initial hospitalization. The patient remained afebrile and leukocytosis resolved with antibiotics. On day 37 of linezolid therapy, serum glucose was 56 mg/dL and serum bicarbonate was 17 mEq/L (normal 23–30 mEq/L). As the patient was asymptomatic, infectious disease consultants recommended cessation of antibiotics, but they were unfortunately continued on transfer to a rehabilitation facility. On day 41 of treatment, the patient became lethargic, with serial serum glucose levels 33–34 mg/dL. Serum bicarbonate was 6 mEq/L, lactate was >15 mmol/L, and blood pressure was 80/36 mm Hg. Admission blood cultures were negative. Supportive care was instituted, but the patient continued to clinically deteriorate. Computed tomography scan of the abdomen showed hepatic steatosis and no residual fluid collections or pancreatic abnormalities. The patient expired on the third day of hospitalization.

Intravenous Versus Oral Omadacycline or Linezolid for Acute Bacterial Skin and Skin Infections: A post hoc Analysis of the OASIS Trials.

Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations. This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7-14days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy. A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47years for the IV-start group and 44years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]). Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies. Clinicaltrials.gov, NCT02378480 and NCT02877927.

Clinical research for saliva-based therapeutic drug monitoring of linezolid.

Linezolid is primarily used to treat of methicillin-resistant Staphylococcus aureus and multidrug-resistant tuberculosis infections. Thrombocytopenia due to linezolid usage is a concern, and therapeutic drug monitoring has been reported to be effective in its prevention. Plasma concentrations provide valuable information for treatment decisions; however, collecting plasma samples can be burdensome for both patients and healthcare providers. Therefore, there is interest in saliva as an alternative for monitoring, considering its potential to replace plasma samples. Patients hospitalized at Hokkaido University Hospital and Hokkaido Spinal Cord Injury Center between April 2022 and July 2024, who received oral or intravenous linezolid treatment, were enrolled. The concentrations of linezolid were simultaneously measured in plasma and saliva samples. We determined the concentration profiles of linezolid in the saliva and examined the correlation between saliva and plasma linezolid concentrations. Eighteen patients receiving linezolid were enrolled. The average of saliva/plasma (S/P) concentration ratios of linezolid were 1.018. A strong correlation was found between the salivary and plasma concentrations of linezolid (R= .833, P< .001). Notably, in patients receiving intravenous administration of linezolid, the correlation was even more pronounced (R= .885, P< .001). Additionally, when focusing on the S/P ratio of the trough concentrations in the morning and at night, the S/P ratios at night were much closer to 1.0. The concentrations of linezolid in plasma and saliva were similar, indicating their potential applicability in clinical settings. The monitoring of linezolid concentrations in saliva has been shown to be particularly suitable for patients receiving intravenous administration.

Release Kinetic of Sustained Release Matrix Tablet of Linezolid Containing Polymer Blend.

Tuberculosis (TB) is a bacterial infection mainly affecting the lungs. TB is a major health problem worldwide and the occurrence of extensively drug-resistant TB (XDR-TB) and multidrug-resistant TB (MDR-TB) offers considerable hurdles to effective treatment and disease management. The growth of treatment-resistant Mycobacterium TB strains has prompted the investigation of alternate therapeutic techniques, including the application of sustained drug delivery. Sustained-release drugs reduce the need for frequent dosing can extend the effects of linezolid by 8 to 12 hours, thus improving the patient’s adherence to the treatment. The objective of this study is to formulate oral sustained-release linezolid tablets employing blends of polymers like hydroxy propyl methyl cellulose (HPMC)- K100M, ethyl cellulose, xanthan gum, and chitosan to provide sustained drug release. Linezolid was made into a sustained-release tablet by employing the direct compression method using different drug-polymer ratios. Formulated tablets were compared with marketed formulations to assess the similarity factor. The formulation was assessed for drug-excipient interaction, solubility, flow properties, etc. The diameter, friability, thickness, hardness, weight variation, in-vitro drug release, and drug release kinetics of compressed tablets were examined. Drug release research proved that all polymers were able to sustain drug release. Formulation (F5) with HPMC (100mg) and ethyl cellulose (100mg) resulted in 49.89% drug release after 8 hours, making it the optimal formulation. According to the kinetic model of the drug release, the Higuchi model was selected, which indicates the diffusion of the drug from an insoluble matrix. The optimized formulation showed a similarity factor of 52% with the marketed formulation, suggesting similarity in drug release between these two formulations.

A case report of empyema caused by Enterococcus gallinarum

BackgroundEnterococcus gallinarum is an infrequently intestinal symbiotic pathogen associated with nosocomial infection in immunocompromised individuals. To date, rare cases of pulmonary infection attributable to Enterococcus gallinarum were reported. Herein, we presented the first case of empyema resulting from Enterococcus gallinarum infection.Case presentationAn 81-year-old male presented with fever and dyspnea upon admission. Chest CT scan and thoracic ultrasonography confirmed the presence of right pleural effusion. Thoracoscopy revealed extensive adhesion, purulent fluid, and necrotic materials within the thoracic cavity. Enterococcus gallinarum was identified through pleural effusion culture. The patient underwent an intrathoracic injection of urokinase along with thoracic drainage. Following surgery, He took oral linezolid for over one month. Undergoing comprehensive treatment, the patient exhibited favorable recovery.ConclusionsWe reported the first case of empyema due to Enterococcus gallinarum infection. It should be suspected in patients with impaired immune function and invasive therapies, without responding to conventional anti-infectious treatment.

Linezolid-Induced Thrombocytopenia in Patients with Renal Impairment: A Case Series, Review and Dose Advice.

Oral linezolid is often used as alternative therapy for intravenous vancomycin. According to the current guidelines, no dose adjustment has to be made in case of renal impairment. Nevertheless, in our hospital we have seen several patients with renal impairment who developed linezolid-induced thrombocytopenia when linezolid was taken in the standard dose. In this case series and review we want to emphasize the necessity of reviewing the Dutch and international guidelines. We describe five cases with renal impairment that developed linezolid-induced thrombocytopenia in our hospital. A PubMed literature review was conducted to identify other cases and find the optimal dosing regimen for these patients. Our cases join a long list of cases and available literature about linezolid-induced thrombocytopenia in patients with renal impairment. Less linezolid-induced thrombocytopenia was found, both in our cases and in the literature, after dose reduction of 50%. High linezolid trough concentrations were associated with a higher risk of linezolid-induced thrombocytopenia. Besides renal impairment, other risk factors for developing linezolid-induced thrombocytopenia were also identified, such as low body weight, high daily dose/kg, higher age, longer duration of therapy, low baseline count, malignity, low-dose aspirin and interacting co-medication. Re-evaluation of the current dose advice is necessary. We advocate for a standard dose reduction to 50% after 2days of standard dosing for all patients with an estimated glomerular filtration of <60mL/min/1.73m2. Besides this, therapeutic drug monitoring and thrombocytes monitoring may be executed weekly when patients have renal impairment or other risk factors for developing linezolid-induced thrombocytopenia.

Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial

Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG). We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than -10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis. Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference -29·6, 95% CI -50·5 to -8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up. The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis. European Research Council and Fondo de Investigaciones Sanitarias.

Assessment of a Pharmacist-Led Antibiotic Time-out for Transition of IV Vancomycin to Oral Linezolid

Assessment of a Pharmacist-Led Antibiotic Time-out for Transition of IV Vancomycin to Oral Linezolid

Hold your Horses! An Uncommon Cause of Bacteremia in HCT Recipients

Abstract Background Diagnosis and management of bloodstream infections due to uncommon microorganisms in immunocompromised hosts (ICH) are challenging. Removing central venous catheters (CVC) and combination antimicrobial therapy may be necessary. Case A 2-year-old female with Mucopolysaccharidosis type I on day +125 after matched unrelated donor allogenic transplant presented with 2 days of decreased activity. Two days prior, she had completed 4 weeks of ciprofloxacin and clarithromycin for treatment of Mycobacterium cosmeticum catheter-related bacteremia (CRBSI). The CVC was removed. The patient lived in a rural area but had no direct animal exposure, except for an indoor vaccinated dog. Household contacts were healthy and immunized. The patient was febrile and tachycardic with no evidence of infection around CVL or G-tube. Laboratory results showed pancytopenia and elevated C-reactive protein Blood cultures grew diphtheroid gram-positive bacilli (GPB) and gram-positive cocci (GPC) in clusters, the later identified as S. epidermidis. The GPB could not be identified from the liquid media and was sent to an outside lab. The report was corrected to GPC after growing on solid medium culture. The patient was started on meropenem and vancomycin and the CVC was removed. The GPB was identified as Rhodococcus equi. A chest CT showed new ground glass nodules in the left lower lobe. The patient defervesced and was discharged on a 10-day course of oral linezolid for S. epidermidis, clarithromycin and levofloxacin. She completed one month of clarithromycin and levofloxacin. Chest CT at end of treatment confirmed resolution. Discussion and conclusions Rhodococcus equi is a pleomorphic gram-positive bacteria that presents as cocci in solid media and as a diphtheroid gram-positive rod in liquid media. Horses are the primary hosts, but most herbivores are fecal carriers. Transmission occurs through inhalation of dust from contaminated soil. R.equi frequently presents as pulmonary infection with cavitated nodules. Over half of ICH develop secondary bacteremia. Extrapulmonary infection secondary to dissemination of pulmonary disease can occur but isolated extrapulmonary disease is rare. R.equi can be easily dismissed as a contaminant requiring a high level of suspicion and communication with lab personnel. When isolated from an extrapulmonary location, chest imagining is essential to guide treatment. Treatment should combine two antibiotics, at least one of them with intracellular activity, with fluoroquinolones and macrolides among the preferred options. For device-related infections, removal is recommended. Treatment duration for uncomplicated infections is 10 to 14 days, but cavitary lesions require longer treatment based on the resolution of lesions

Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial

Around 500 000 people worldwide develop rifampicin-resistant tuberculosis each year. The proportion of successful treatment outcomes remains low and new treatments are needed. Following an interim analysis, we report the final safety and efficacy outcomes of the TB-PRACTECAL trial, evaluating the safety and efficacy of oral regimens for the treatment of rifampicin-resistant tuberculosis. This open-label, randomised, controlled, multi-arm, multicentre, non-inferiority trial was conducted at seven hospital and community sites in Uzbekistan, Belarus, and South Africa, and enrolled participants aged 15 years and older with pulmonary rifampicin-resistant tuberculosis. Participants were randomly assigned, in a 1:1:1:1 ratio using variable block randomisation and stratified by trial site, to receive 36-80 week standard care; 24-week oral bedaquiline, pretomanid, and linezolid (BPaL); BPaL plus clofazimine (BPaLC); or BPaL plus moxifloxacin (BPaLM) in stage one of the trial, and in a 1:1 ratio to receive standard care or BPaLM in stage two of the trial, the results of which are described here. Laboratory staff and trial sponsors were masked to group assignment and outcomes were assessed by unmasked investigators. The primary outcome was the percentage of participants with a composite unfavourable outcome (treatment failure, death, treatment discontinuation, disease recurrence, or loss to follow-up) at 72 weeks after randomisation in the modified intention-to-treat population (all participants with rifampicin-resistant disease who received at least one dose of study medication) and the per-protocol population (a subset of the modified intention-to-treat population excluding participants who did not complete a protocol-adherent course of treatment (other than because of treatment failure or death) and those who discontinued treatment early because they violated at least one of the inclusion or exclusion criteria). Safety was measured in the safety population. The non-inferiority margin was 12%. This trial is registered with ClinicalTrials.gov, NCT02589782, and is complete. Between Jan 16, 2017, and March 18, 2021, 680 patients were screened for eligibility, of whom 552 were enrolled and randomly assigned (152 to the standard care group, 151 to the BPaLM group, 126 to the BPaLC group, and 123 to the BPaL group). The standard care and BPaLM groups proceeded to stage two and are reported here, post-hoc analyses of the BPaLC and BPaL groups are also reported. 151 participants in the BPaLM group and 151 in the standard care group were included in the safety population, with 138 in the BPaLM group and 137 in the standard care group in the modified intention-to-treat population. In the modified intention-to-treat population, unfavourable outcomes were reported in 16 (12%) of 137 participants for whom outcome was assessable in the BPaLM group and 56 (41%) of 137 participants in the standard care group (risk difference -29·2 percentage points [96·6% CI -39·8 to -18·6]; non-inferiority and superiority p<0·0001). 34 (23%) of 151 participants receiving BPaLM had adverse events of grade 3 or higher or serious adverse events, compared with 72 (48%) of 151 participants receiving standard care (risk difference -25·2 percentage points [96·6% CI -36·4 to -13·9]). Five deaths were reported in the standard care group by week 72, of which one (COVID-19 pneumonia) was unrelated to treatment and four (acute pancreatitis, suicide, sudden death, and sudden cardiac death) were judged to be treatment-related. The 24-week, all-oral BPaLM regimen is safe and efficacious for the treatment of pulmonary rifampicin-resistant tuberculosis, and was added to the WHO guidance for treatment of this condition in 2022. These findings will be key to BPaLM becoming the preferred regimen for adolescents and adults with pulmonary rifampicin-resistant tuberculosis. Médecins Sans Frontières.

Aortic endograft infection by Mycobacterium abscessus subsp. massiliense with acquired clarithromycin resistance: a case report

BackgroundMycobacterium abscessus subsp. massiliense (MMA) comprises a group of non-tuberculous, rapidly growing mycobacteria. Although MMA can cause pulmonary diseases, surgical site infections, and disseminated diseases, aortic endograft infection has not been reported. Here, we describe the first case of aortic endograft infection caused by MMA.Case presentationTwo months after stent-graft insertion for an abdominal aortic aneurysm, an 85-year-old man was admitted with fever and abdominal pain and was diagnosed with aortic endograft infection. Despite 14 days of meropenem and vancomycin intravenous administration, periaortic fluid pooling increased as compared to that before antibiotic administration. The abscess was drained, and fluorescent acid-fast staining of the abscess fluid revealed bacilli. We conducted genetic tests on the genes hsp65, rpoB, and sodA, performed Whole Genome Sequencing (WGS), and identified the organism as MMA. Intravenous imipenem–cilastatin (IPM/CS), amikacin (AMK), and oral clarithromycin (CAM) were administered. After 2 months, oral CAM and sitafloxacin were administered because the abscess had decreased in size. However, after 6 weeks, the abscess increased in size again. Antimicrobial susceptibility testing of the drainage fluid from the abscess resulted in the isolation of an MMA strain that had acquired resistance to CAM. Intravenous IPM/CS, AMK, and oral linezolid were added to the treatment regimen along with oral CAM and STFX. However, he was not fully cured and died 6 months later. Neither the full-length erythromycin ribosome methyltransferase (erm)(41) gene nor the rrl or rpIV gene mutations were found by Sanger sequencing in the pre- and post-treatment strains. Whole-genome sequence analysis of the post-treatment strain revealed mutations in genes with no previous reports of association with macrolide resistance.ConclusionsAortic endograft infection caused by MMA strain is extremely rare; nonetheless, MMA should be suspected as the causative microorganism when broad-spectrum antimicrobials are ineffective.

Clinical Pharmacology of Antimicrobials: Focus on the Safety of Vancomycin and Linezolid

Scientific relevance. Vancomycin and linezolid are the antibacterial agents of choice for severe infections caused by multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). However, few studies have been conducted in Russia to analyse the safety of these medicinal products.Aim. The study aimed to compare the safety of vancomycin and linezolid using the Moscow segment of the Russian Federal Service for Surveillance in Healthcare’s database for adverse drug reaction (ADR) reports.Materials and methods. The study used information from the spontaneous reporting database for 2018–2022, which contained 147 ADR reports for vancomycin (122 reports) and linezolid (25 reports). The authors analysed the ADR distribution and assessed the statistical significance of the identified differences by sex, weight, and age of patients, conditions of medical care, route of administration, single dose, daily dose, therapy duration, ICD-10 codes, ADR severity, and ADR outcome.Results. The distribution of adverse reactions to vancomycin and linezolid by patient age was relatively uniform. Outpatient linezolid was associated with a significantly higher rate of ADRs (3 of 5 reports) than outpatient vancomycin (21 of 129 reports; p=0.0408). For ADR severity, 5 of 20 ADRs reported with linezolid required hospitalisation or prolongation of hospitalisation—considerably more than with vancomycin (16 of 94 reports; p=0.528). The average single dose of vancomycin (794 mg) was higher than that of linezolid (467 mg; p=0.007); the same was noted for average daily doses (1273 mg vs 998 mg; p=0.3664). The mean duration of treatment with linezolid before ADR onset was 5.26 days, which was significantly longer than the mean duration of treatment with vancomycin (2.44 days; p=0.0053). Oral linezolid was associated with a significantly higher ADR rate (4 of 19 cases) than oral vancomycin (5 of 96 cases; p=0.0027).Conclusions. The ADRs observed with vancomycin and linezolid were predictable and class-specific. According to the results of the ADR report analysis, adverse reactions to vancomycin and linezolid were associated with different factors. Similar results of the literature analysis confirmed this conclusion. However, according to the results of the linear regression analysis, none of the factors considered in this study had a statistically significant influence on the probability of developing an adverse reaction to vancomycin or linezolid.

Two-Stage Revision Arthroplasty for Resistant Gram-Positive Periprosthetic Joint Infections Using an Oral Linezolid-Based Antibiotic Regime.

Increasing antibiotic resistance has been reported as an issue in the systemic treatment of periprosthetic joint infection (PJI). Linezolid offers the advantages of high oral bioavailability and little resistance; however, efficacy in the treatment of PJI varies considerably, and studies reporting consistent surgical treatment are scarce. This is a retrospective, single-center analysis of two-stage revisions performed between 2008 and 2017. We identified 111 patients who met the inclusion criteria. Oral linezolid was given for 28 days following 14 days of intravenous tailored antibiotics in resistant gram-positive PJI. A total of 64% of the patients had methicillin-resistant coagulase-negative staphylococci. The median follow-up was 43 (interquartile range (IQR) 30-57) months. 22% (24/111) of the patients underwent surgery for subsequent infection. The 5-year infection-free survival probability was 77% (95% confidence interval (CI) 69-85). A total of 5% of the patients (6/111) had the same organism at the time of reinfection. The patients with infections caused by other organisms than Coagulase-negative staphylococci tended to have a worse reinfection-free survivorship at five years (70% vs. 81%, p = 0.09). Furthermore, the patients with obesity tended to have reduced reinfection-free survivorship at five years (69% vs. 84%, p = 0.08). Overall, 5% (6/111) of the patients had blood count abnormalities with no treatment discontinuations. Two-stage revision arthroplasty with systemic oral linezolid treatment for resistant gram-positive PJI results in an infection control of 77% at the mid-term.

BG08 Successful treatment of recalcitrant Darier disease with ustekinumab

Abstract Darier disease (DD) is a genodermatosis characterized by hyperkeratotic greasy papules in a seborrhoeic distribution. DD is caused by dominant mutations in ATP2A2, responsible for encoding the SERCA2 calcium pump. Currently, there are no licensed treatments for DD, but there is emerging evidence for the role of dysfunctional inflammation in DD. Our patient was a 49-year-old White woman with a history of recalcitrant DD involving extensive sheets of raw eroded skin. There was a strong family history of DD; her mother and maternal uncle had both died from sepsis related to DD. She suffered from recurrent superimposed skin infections, including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas species and herpes simplex virus. Between 2019 and 2021, she required eight prolonged hospital admissions (average duration of stay 21 days; range 4–44) for intensive topical treatments (including potent topical steroids, emollients, topical antimicrobial agents and topical anaesthetic agents) and microbiology-guided systemic antimicrobial therapy [including oral co-amoxiclav, intravenous (IV) flucloxacillin, IV piperacillin–tazobactam, oral linezolid, IV daptomycin and oral valaciclovir]. She routinely required admission to the high-dependency unit for sepsis management, with multidisciplinary input from specialists in internal medicine, pain management, psychiatry and physiotherapy to enhance her recovery and optimize her associated comorbidities. Repeat biopsies were performed to confirm her diagnosis and rule out secondary viral infection or malignancy. Multiple systemic agents were trialled unsuccessfully, including acitretin, isotretinoin, alitretinoin, dapsone, ciclosporin and apremilast. Owing to the inflammatory presentation of her dermatosis and emerging evidence on the role of T helper 2-mediated inflammation in DD, the anti-interleukin (IL)-12/IL-23 agent ustekinumab was added to her regular treatment regimen. This successfully resulted in inducing disease remission within 5 months, with no further requirements for acute hospital admission or IV antimicrobial therapy in the year since initiation. Ustekinumab has never previously been reported for the treatment of DD in the literature. There have been individual reports of other inflammation-targeted agents such as IV methylprednisolone, immunoglobulin and ciclosporin, but treatment was poorly tolerated and relapse occurred following discontinuation. Penicillamine, doxycycline, oral contraceptive agents and oral magnesium have also been examined as potential therapeutic agents. Proinflammatory cytokines, in particular tumour necrosis factor-α and IL-6, have been associated with viral superinfection in DD, suggesting that systemic inflammation may closely relate to skin infections and disease activity in DD. In addition, cultured keratinocytes treated with IL-6 demonstrate reduced expression of ATP2A2. Ustekinumab may be a promising choice as a systemic immunomodulatory agent for DD. Future studies should examine the immune profile of patients with DD to inform therapeutic strategies.

Successful Treatment of Sthaphylococcus Peritonitis Using Oral Linezolid Without Catheter Removal in a Peritoneal Dialysis Patient

Peritonitis is one of the main complications of peritoneal dialysis and accounts for considerable mortality and hospitalization. It is usually treated with intraperitoneal antibiotherapy, as it is the best way to achieve high concentrations at the site of infection. We report a case of an 86-year-old female patient with end-stage renal disease under continuous ambulatory peritoneal dialysis, who was admitted to our hospital with complaints of intense diffused abdominal pain. The effluent culture yielded Staphylococcus hominis only sensible to vancomycin and linezolid. She was diagnosed with peritonitis secondary to Staphylococcus hominis infection and treated with oral linezolid without catheter removal. Adequate linezolid peritoneal fluid concentration (between 3 and 20 µg/mL) was achieved and the antibiotic therapy was maintained for 21 days with clinical and analytical improvement. According to our knowledge, this was the first Staphylococcus peritonitis in a peritoneal dialysis patient, successfully treated with oral linezolid and has had linezolid levels monitored in the peritoneal dialysis effluent.

Treatment of long-term catheter-related bloodstream infections with short-course Daptomycin lock and systemic therapy associated with Taurolidine-lock: A multicenter experience.

Few studies describe the efficacy of antibiotic lock therapy (ALT) in long-term catheter-related bloodstream (CRBSI) infections. We applied local protocols combining Daptomycin (DPT) and Taurolidine ALT, associated with systemic antibiotic treatment (SAT), for conservative management of coagulase-negative Staphylococci (CoNS) CRBSI. Patients admitted for CoNS-associated CRBSI and treated with DPT and Taurolidine as ALT were retrospectively analyzed. Success was defined as catheter retention 30 days after ending treatment. Catheter removal within 30 days was considered as failure. From April 2018 to September 2021, 22 subjects with CoNS-associated-CRBSI were included (95% with cancer, mean age 64 years, 59% male). Staphylococcus epidermidis was isolated in 82% of cases. Mean duration of DPT was 3.9 and 3 days as ALT and SAT, respectively. SAT also included Rifampin for 3 days. Taurolidine ALT was started on day 4 and was combined with oral SAT, that is, either Linezolid or Tedizolid. Mean duration of Taurolidine was 10.5 days, while total antibiotic treatment lasted 13.5 days. Clinical success and failure rates were 95% and 5%, respectively. Short course DPT as ALT, combined with SAT and Taurolidine ALT, allowed high rates of conservative management of catheters in case of CoNS-associated-CRBSI.

Novel six-month all oral treatment of pre-extensively drug-resistant tuberculosis in Canada: New treatment options present new implementation challenges.

Drug-resistant tuberculosis (TB) is a major global health challenge in part because there are fewer effective treatments and these treatments have been prolonged and more toxic. The evidence base for more effective, shorter, standardized treatments is evolving rapidly. Herein, we report the first case of pre-extensively drug-resistant pulmonary TB treated with a novel six-month all oral bedaquiline, pretomanid and linezolid (BPaL) regimen in Canada. Recent clinical trial data supporting BPaL therapy is presented in the context of current and evolving clinical guidelines. In this article, we highlight significant implementation challenges and make recommendations for what needs to be addressed to ensure safe programmatic use of BPaL in Canada. Key recommendations include the development of infrastructure for timely access to novel TB drug susceptibility testing, streamlining access to novel TB drugs, and cautious use of such drugs in collaboration with care teams with expertise in drug-resistant TB management.

Impact of a Pharmacist-Managed Outpatient Parenteral Antimicrobial Therapy (OPAT) Service on Cost Savings and Clinical Outcomes at an Academic Medical Center.

Outpatient antimicrobial therapy (OPAT) is managed by a variety of teams, but primarily through an infectious disease clinic. At our medical center, OPAT monitoring is performed telephonically by pharmacists through a collaborative practice agreement under the supervision of an infectious disease physician. The effect of telephonic monitoring of OPAT by pharmacists on patient outcomes is unknown. This retrospective cohort study was conducted between July 2017 and July 2018 at a 350-bed academic medical center and included adult patients discharged home on IV antibiotics or oral linezolid. The experimental group comprised patients discharged with a consultation for the OPAT management program, whereas the control group comprised patients discharged home without a consultation. The primary outcome was 30-day readmission. In total, 399 patients were included: 243 patients in the OPAT management program group and 156 patients in the control group. The 30-day readmission rates were similar in each cohort (20% vs 19%; P = .8193); however, the 30-day readmission rates were lower in the OPAT management program for patients discharged on vancomycin (19.4% vs 39.1%; P = .004). We did not find a difference in 30-day readmissions between patients receiving pharmacy-driven OPAT management services and those who did not. Patients receiving vancomycin via OPAT had lower 30-day readmissions when included in the pharmacist-driven OPAT management program. Institutions with limited resources may consider reserving OPAT management services for patients receiving antimicrobials that require pharmacokinetic dosing and/or close monitoring.

Successful Management of an Acute Case of Orbital Cellulitis of Odontogenic Origin.

Sir, Dental infections left untreated can progress through tissue planes into the orbital space through sinuses and result in orbital abscess which is an ophthalmic emergency. We describe the case of a 47-year-old female, a known diabetic who presented with complaints of severe swelling and pain in periorbital region, associated with fever, vomiting, and prostration for 20 days’ duration. She gave a history of repeated episodes of dental pain arising out of her impacted upper third molar tooth for the past 2 months. Ocular examination of the right eye showed significant proptosis of 24 mm, restriction of extraocular movements in all directions, normal pupillary reaction with best-corrected visual acuity of 6/24, and intraocular pressure of 21 mm of Hg [Figure 1a]. Magnetic resonance imaging (MRI) showed heterogeneous multifocal lesions in the right orbit with T1 hypointensity, T2 hyperintensities with internal septation in the intra-conal and extraconal compartments producing compression over the globe [Figure 1b]. Dental X-ray was suggestive of impacted right maxillary third molar tooth [Figure 1c]. On the second day of her hospital stay, she developed multiple upper and lower eyelid pre-septal and post-septal abscesses which were drained, and the pus was sent for culture and sensitivity. Systemic antibiotics were started in the form of intravenous piperacillin/tazobactam (4.0/0.5 g) 8 hourly, metronidazole (500 mg/100 ml) 8 hourly, and oral linezolid (600 mg) 12 hourly. Blood sugars were monitored and insulin was administered as per her requirement. She was referred to dental surgeon for extraction of the impacted molar tooth. She recovered completely with best-corrected visual acuity of 6/9 and intraocular pressure of 16 mm of Hg. She showed remarkable improvement at 2 weeks after tooth extraction [Figure 1d].Figure 1: (a) Clinical photograph at presentation showing severe proptosis, complete ptosis, erythema, restricted extraocular movements, and pus pointing over lower eyelid skin. (b) MRI sagittal section T1 image showing multiloculated abscesses in intraconal and extraconal compartment of right orbit causing compression of eyeball. (c) Right maxillary posterior intraoral periapical radiograph showing impacted upper third molar tooth. (d) Clinical photograph of the same patient after two weeks with complete resolution of edema, proptosis, and extraocular movements. MRI: Magnetic resonance imagingOrbital cellulitis secondary to dental infection is rare accounting for 2%-5% of all cases of orbital infections.[1] To add to its rarity, orbital abscess constitutes less than 1.3% of abscesses seen in maxillofacial region.[2] Surgical drainage of the abscess and pus sample collection is a recommended modality of treatment as reported by many authors.[3,4] Empirical antibiotics and proper intravenous fluid hydration are mainstay of treatment. Systemic corticosteroids fasten the resolution of inflammation and duration of hospital stay.[5] A multidisciplinary approach with dentists, diabetologists, and ophthalmologists is required to prevent serious complications of venous sinus thrombosis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Research quality and ethics statement The authors followed applicable EQUATOR Network (http://www.equator-network.org/) guidelines, notably the CARE guideline, during the conduct of this report. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.