Course Of Antibiotics Research Articles

VS 09 - HPB Laparoscopic Trans-Cystic Bile Duct Exploration is Safe and Feasible even after previous Cholecystectomy

Abstract Background Laparoscopic trans-cystic bile duct exploration is well know to have less comorbidity that conventional trans-ductal approach. A 56-year-old female underwent emergency laparoscopic cholecystectomy in 2019 for cholecystitis. Subsequently treated conservatively for ascending cholangitis due to large stone in the bile duct on MRCP. She underwent two unsuccessful ERCPs due to anatomical challenges; large hiatus hernia and duodenal diverticulum. The MDT determined bile duct exploration was necessary as no endoscopic options remained. After assessing previous imaging, laparoscopic trans-cystic exploration was chosen to minimise complications. This video highlights the feasibility of laparoscopic trans-cystic CBD post-cholecystectomy. Method Standard four-port technique with 10mm, 30-degree laparoscope. Blunt, sharp, energised and hydro-dissection were employed. Indocyanaine green(ICG) helped identify the bile duct(CBD) and the cystic duct(CD) stump. CD was dissected from the gallbladder bed and opened for a cholangiogram; confirming a large stone in the distal bile duct. A 3.5 mm choledochoscope with electrohydraulic lithotripsy(EHL) was used to explore the bile duct and fragment the stone for extraction. Remaining small fragments were flushed into the duodenum after 20mg buscopan intravenously. Final cholangioscopy and cholangiogram through the choledochoscope showed clear ducts with good flow into the duodenum. Results The patient was started on IV antibiotics due to pyrexia on the first night of admission. The abdominal drain was removed after 48 hours, and the patient was discharged on day three to complete a five-day course of antibiotics. Nine months post-operatively, she presented with a 3x5x7.5 cm sub-hepatic abscess, requiring interventional radiology (IR) drainage and a six-week course of antibiotics. The drain was removed after a follow-up CT scan three weeks post-drainage showed resolution. There have been no further episodes of cholangitis, and she has returned to her baseline quality of life. Conclusion This case shows laparoscopic trans-cystic approach remains viable post-cholecystectomy. Advanced imaging and tools including 3.5mm choledochoscope and EHL aid safer surgery with reduced morbidity, shorter stays and faster recovery. Antibiotics may be necessary for cases with longstanding bile duct stones. Furthermore, this case highlights the importance of intraoperative cholangiography and bile duct exploration. The patient had an MRCP in 2019 that showed no bile duct stones but a dilated CBD associated with deranged LFTs. This suggests that her journey might have been less complicated if a cholangiogram had been performed during the initial laparoscopic cholecystectomy.

Navigating antibiotic therapy in acute cholangitis: Best practices and new insights.

Globally, antibiotic resistance is linked to increased morbidity, mortality, and healthcare costs, which necessitates further research on optimal antibiotic usage. Acute cholangitis (AC), a common cause of community-acquired bacteremia, often requires antimicrobial therapy. Therefore, studying the appropriate use of antibiotics for AC is considered crucial for suppressing the emergence of resistant bacteria and reducing adverse antibiotic-associated events. The Tokyo Guidelines 2018 (TG18) recommend 4-7 days of antibiotics post-biliary drainage. However, this lacks strong evidence and is based primarily on various evidence and expert opinions. Recent retrospective studies advocate for a shorter 1-3-day antibiotic course for AC, thereby prompting a need to reassess the treatment duration to balance therapeutic efficacy and minimize resistance and adverse effects. Choosing the appropriate duration and antibiotics based on susceptibility to pathogens causing cholangitis is important. Awareness of local resistance patterns and understanding patients' risks of resistant pathogens are prerequisite for effective treatment. We must explore the applicability of these guidelines in specific scenarios such as severe AC, positive blood cultures, fever, or hilar biliary obstructions due to malignancy. This comprehensive review considers both the duration and type of antibiotics and aims to enhance treatment outcomes while reducing the risk of resistant bacterial infections.

HPB SO02 - Cutting surgical site infection rates in perihilar cholangiocarcinoma with informed changes to perioperative antibiotic prophylaxis: A quality improvement project in a UK hepatopancreatobiliary tertiary centre

Abstract Background Perihilar cholangiocarcinoma (pCCA) is the most common cancer of biliary epithelia. While potentially curative, surgical resection is associated with high morbidity and mortality. Surgical site infections (SSIs) are common and pernicious. Preoperative biliary instrumentation is universal: to confirm histological diagnosis and deploy stents to relieve jaundice. Patients receive multiple antibiotic courses as periprocedural prophylaxis and to treat cholangitis. They are at high risk of harbouring bacteria not quelled by perioperative prophylactic antibiotics given for other general surgical procedures. Studying the biliary microbiome, this quality improvement project sought to reduce SSIs through informed changes to local guidelines on perioperative antibiotic prophylaxis. Method Health records of all patients undergoing resection for pCCA in a UK hepatopancreatobiliary centre from February 2009 to January 2024 were analysed retrospectively (n=118). For all patients, we routinely sent intraoperative bile swabs for culture and sensitivity. Informed by these microbiology results, multidisciplinary discussion led to changes to local guidelines in March 2019. Formerly, cefuroxime and metronidazole were given on anaesthetic induction, with subsequent antibiotic choice and duration according to surgeon preference. New guidance stipulated teicoplanin and piperacillin/tazobactam be given on induction and for 72 hours postoperatively. We studied the impact of these changes on SSIs within 30 days. Results 75 patients received cefuroxime and metronidazole; 43 patients were given teicoplanin and piperacillin/tazobactam after the policy change. Proportions of patients who developed any SSI substantially fell following the guideline change (55% v 28%; p=0.0049), primarily owing to reductions in intraperitoneal collections (39% v 21%; p=0.047). Rates of deep (8% v 2%; p=0.21) and superficial incisional infections (8% v 5%; p=0.49) were not significantly affected. Associated secondary outcomes were drops in post-hepatectomy liver failure (17% v 5%; p=0.047), and 90-day mortality (16% v 5%; p=0.067), albeit the latter was not statistically significant. Conclusion Invasive investigative work-up, disease complications and exposure to multiple courses of antibiotics prior to resection of pCCA subject patients’ biliary systems to colonisation with antimicrobial-resistant bacteria. We urge centres that undertake these operations to introduce intraoperative bile cultures as a part of routine practice to inform local guidance on perioperative antimicrobial prophylaxis. We demonstrated effective antibiotics in the perioperative period can have enormous benefits to patient outcomes.

Duration of Antimicrobial Treatment in Adult Patients with Pneumonia: A Narrative Review

Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of treatment duration on clinical outcomes demonstrates that shorter antibiotic courses are non-inferior, regarding safety and efficacy, compared to longer courses, particularly in patients with mild to moderate CAP, which is in line with the recommendations of international guidelines. Data are limited regarding the optimal antimicrobial duration in HAP patients, and it should be individually tailored to each patient, taking into account the causative pathogen and the clinical response. Shorter courses are found to be as effective as longer courses in the management of VAP, except for pneumonia caused by non-fermenting Gram-negative bacteria; however, duration should be balanced between the possibility of higher recurrence rates and the documented benefits with shorter courses. Additionally, the validation of reliable biomarkers or clinical predictors that identify patients who would benefit from shorter therapy is crucial. Insights from this review may lead to future research on personalized antimicrobial therapies in pneumonia, in order to improve patient outcomes.

Abstract 4138717: Infective Root Aortitis: Medical Therapy Alone or Medical Therapy and Surgery?

Clinical presentation: A 75-year-old male with previous 3 vessel CABG and bioprosthetic aortic valve (BAV) surgical replacement in 2013 was admitted with severe sepsis from diabetic foot ulcer complicated with Group A Streptococcus bacteremia and infective root aortitis. Imaging Findings: Initial technically limited transthoracic echocardiogram was followed by a transesophageal echocardiogram (TEE) that demonstrated a well seated BAV with mildly thickened leaflets but no vegetations, mild intra-valvular regurgitation, and 9 mm end-diastolic soft tissue echoreflectant thickening of the posterior aortic root (AoR) extending up 3 cm from the aortic annulus to the ascending aorta (Fig 1A,B). There were no signs of perivalvular abscess formation. Initial FDG PET-CT demonstrated heterogenous hypermetabolic activity at the annulus of the BAV (Fig 1C) and AoR (Fig 1D) consistent with aortitis. Decision-making: In the absence of guidelines for the management of these patients, a multidisciplinary team including cardiology, cardiothoracic surgery, and infectious disease opted for a conservative medical therapy instead of high-risk surgery. Patient then underwent left foot first digit amputation to achieve infectious source control. Upon completion of 4 out of 6 weeks of intravenous ceftriaxone 2 grams daily, repeat TEE showed improved AoR thickening to 6 mm (Fig 1E,F), no AoR abscess, and unchanged BAV structure and function. Repeat FDG PET-CT at the same time of TEE demonstrated persistent but improved hypermetabolic activity of the BAV annulus and AoR. After 10 weeks of IV antibiotics, repeat FDG PET-CT showed further decrease in metabolic activity on both areas. However, an Indium-111 labeled leukocyte scan showed no activity at the BAV annulus and root (Fig 1G) and therefore indicated healed AoR aortitis, which was further supported by significant decrease of ESR and CRP initial values of 126 mm/hr and 122.7 mg/L to 11 mm/hr and 3 mg/L, respectively. Patient is currently clinically stable 8 months later. Conclusion: This case illustrates that a conservative management of infective AoR aortitis with an extended course of intravenous antibiotics is a reasonable alternative to high-risk re-do valve and root surgery.

External evaluation of intravenous vancomycin population pharmacokinetic models in adults receiving high-flux intermittent haemodialysis.

Patients undergoing haemodialysis (HD) are at greater risk of methicillin-resistant Staphylococcus aureus infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model-informed dosing is commonly used. This study aimed to perform an external evaluation of published vancomycin popPK models developed for adults undergoing high-flux intermittent HD, and to create a dosing nomogram derived from the model that performed best. A literature review was conducted through PubMed and EMBASE to identify relevant popPK models. an external dataset was collected retrospectively from patients of 2 healthcare centres in Quebec, Canada. Selected models were implemented in NONMEM (v7.5; ICON Development Solutions). Predictive performance was assessed through prediction and simulation-based diagnostics. In total, 2386 vancomycin concentrations were collected from 274 patients and 476 antibiotic courses. Four vancomycin popPK models were selected for evaluation. None of the models demonstrated overall satisfactory or clinically acceptable predictive performance. Nonetheless, Bae et al.'s model performed best with a median prediction error of 16.25% and median absolute prediction error of 34.66%. Different predictive performance was also observed for vancomycin concentrations from samples collected during and between HD sessions. All evaluated models presented poor overall predictive performance. Further studies are required, through existing popPK model parameter re-estimation or new model development, to adequately describe vancomycin pharmacokinetics for our high-flux intermittent HD patient cohort.

Antimicrobial stewardship in sub-Saharan African community pharmacies: a systematic review of community pharmacists’ knowledge, practice and challenges faced

Abstract Introduction The indiscriminate use of antimicrobials contributes significantly to antimicrobial resistance (AMR). The World Health Organization (WHO) recommends antimicrobial stewardship (AMS) as one of the global sustainable development interventions to tackle AMR. Implementation of AMS interventions have been documented to be successful in high-income countries 1, however, there is paucity of data regarding the implementation and effectiveness of AMS in low-income settings including sub-Sahara Africa (SSA). Community pharmacies in the SSA play a critical role in the dispensing of medicines, including antibiotics. Aim To evaluate community pharmacists' knowledge, practice, and challenges faced in relation to AMS in SSA community pharmacies. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) framework guided the review. We searched six electronic databases (PubMed, Web of Science, ProQuest Central, Google Scholar, African Journal Online and Wiley Online library) from January 2010 to December 2022. Reference lists of included articles were screened for additional studies. Studies published in English that described AMS interventions, antibiotic dispensing practices, community pharmacists’ knowledge and perceptions of AMS/AMR were included. Literature reviews and systematic reviews were excluded. AMS in hospital pharmacy and animal studies were also excluded. Two reviewers independently screened the abstracts and full texts according to pre-defined inclusion criteria. Disagreements were resolved through discussion. The Mixed Methods Appraisal Tool (MMAT) was employed to assess the quality of the included studies2. Data were extracted using a standardised form in Microsoft excel and double checked for accuracy. Data were synthesised using narrative synthesis. The review protocol was registered with PROSPERO (CRD42023381320). The study did not require ethical approval because it did not involve conducting primary or secondary research involving human participants. Results The review identified 1972 articles, of which 23 studies met the inclusion criteria. Studies varied in settings, design, and data collection methods. Two broad categories were identified from the narrative synthesis. (1) Community pharmacists’ knowledge, attitude, perception, and dispensing practices (n=20). Studies reported that community pharmacists displayed an understanding of how antibiotics work. They also acknowledged threats posed by AMR. Some studies reported misconceptions on clear guidelines about the practical implementation of AMS, other studies described good adherence to antibiotic dispensing practices, including taking medication histories, assessing symptoms, advising on completion of antibiotic courses and making referrals. One study described the perception of community pharmacists of AMS as crucial for improving patient care. (2). Determinants of non-prescription antibiotic sales (n=3). The studies explored factors influencing the sale of antibiotics without prescription. Studies identified pharmacy owners’ expectations (profitability) and lack of public awareness regarding the risks of non-prescription antibiotic use as contributing factors. Limited patient access to doctors and low economic status in SSA were also cited as determinants. Conclusions Community pharmacists have knowledge of antibiotics, and they also acknowledged the importance of AMS. There were also positive dispensing practices despite existing challenges regarding implementation of AMS and sales of antibiotics without prescription. Further research should prioritize well-designed studies that evaluate the effectiveness of AMS in this setting and address the challenges identified. Heterogeneity of study methods limits the generalisability of findings.

Antibiotic prescribing in health and justice settings (HJS)-surveillance and opportunities for quality improvement

Abstract Introduction Improving surveillance of antibiotic prescribing and reducing health inequalities in antimicrobial resistance (AMR) are priorities in the new 5 year AMR national action plan (2024-2029)1. People in contact with the justice system are one of the inclusion groups in the CORE20plus5, a national NHE England approach to support reduction of health inequalities.2 Aim This project aimed to collate and analyse all antibiotic prescribing data from English prisons in order to identify opportunities for quality improvement. Method This project analysed antibiotic prescribing data from September 2022 to current date for the first time in HJS from the IT system used in all prisons in England. No ethical approval is required as surveillance is of anonymised data only. Data was broken down by age band (18 and under, 19-49, 50 and over), category of prison, region, ICB, individual prison and antibiotic type. The dashboard allows benchmarking across sites and comparison with primary care, as prisoners in HJS are considered to have similar infections to primary care patients. Results The majority of prescribing is in male prisoners, reflecting the male/female population split. The most frequently prescribed antibiotics are those used for: skin and soft tissue (including acne), respiratory tract, dental and urinary tract infections. A number of focus areas for quality improvement have been identified, including: Broad spectrum antibiotics (Cephalosporins, Co-amoxiclav and Quinolones), target of <10% total antibiotic prescribing in primary care, in HJS, currently 11%. Appropriate quinolone prescribing is a target in all settings due to recent MHRA alert3. Acne prescribing represents a significant proportion of antibiotic prescribing in HJS. Lymecycline 12%, whereas in primary care <3%. Duration of Antibiotic Courses: In primary care there is a medicines optimisation opportunity ambition to achieve 75% prescribing amoxicillin 500mg as 5 day duration. In HJS only 27% is for 5 days. When prescribing 100mg doxycycline for respiratory infections, NICE guidance recommends a 5 day course, but in HJS only 3% is prescribed as a 5 day course. For UTI in female prisons, nitrofurantoin 100mg MR is most commonly prescribed, NICE guidance for UTI in women is for 3 days; 47% in HJS are for 3 days, but 35% are 7 day courses. Discussion and Conclusion This dashboard provides insight into antibiotic prescribing data allowing opportunities for quality improvement opportunities to be identified and antimicrobial stewardship interventions to be evaluated. This work will progress to tackle the focus areas identified. Next steps are to work with antibiotic champions from HJS to co-produce intervention plans, share patient safety messages, trial available resources, rollout interventions and monitor impact via the dashboard. Limitations Indications are not available from the data but extrapolated from the antibiotic prescribed. The dashboard is currently an excel spreadsheet in NHSE. It will be moved to a platform that enables access by individual prisons.

Shorter courses of antibiotics.

Shorter courses of antibiotics.

Antibiotic-associated neutropenia is marked by the depletion of intestinal Lachnospiraceae and associated metabolites in pediatric patients.

Prolonged antibiotic exposure causes dangerous hematologic side effects, including neutropenia, in up to 34% of patients. Murine studies established a link between the intestinal microbiota and hematopoiesis. To identify factors that predispose to neutropenia in pediatric patients, we evaluated changes in microbiota-derived metabolites and intestinal microbiota composition after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics or at neutropenia onset (prospective arm). Some patients were enrolled in a retrospective arm in which a stool sample was collected at the time of neutropenia during antibiotic therapy and 2-4 weeks after completion of antibiotics with recovery of blood counts. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and the type of infection or antibiotic used; however, patients with neutropenia were admitted to the intensive care unit more often and received longer courses of antibiotics. Reduced intestinal microbiome richness and, specifically, decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism, and fatty acid metabolism that are known to be produced by Lachnospiraceae. Our study shows a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis.

P35 Pyrexia of unknown origin in a patient with long standing rheumatoid arthritis

Abstract Introduction Pyrexia of unknown origin (PUO) can be challenging in treated rheumatic auto-immune disease. Many conditions may have fever as part of the symptom complex, treatment may mask signs and symptoms and can also make opportunistic infection more likely. Unusual or fastidious infections can be particularly difficult to diagnose. We describe a case of ureaplasma infection that evaded detection for a prolonged period in a female with long standing rheumatoid arthritis (RA). Case description 47 year old female presented January 2023 with fevers, weight loss and persistently high CRP. RA diagnosed in 1998. Erosive wrist and MTP disease, initial RF 32, CCP 8. Treatment- 5-10 mg prednisolone since 1998, adalimumab 2010, rituximab 2013-2022. Normal Ig levels, IgG lamda paraprotein since 2016 (too low to quantify). Frequency and dysuria March 2022. Cystoscopy- small bladder; biopsies in May 2022 and August 2023 showed acute on chronic inflammatory infiltrate with granulation tissue. Interstitial cystitis diagnosed. She had recurrent episodes of pyuria and was given several courses of antibiotics, including meropenem, temocillin, fluconazole, gentamicin. Despite the recurrent pyuria no organisms were cultured. CT CAP February 2023 -ground glass opacity right lower lobe. Later CXR clear. Quantiferon negative, also negative 2016, 2019. Other normal / negative tests- TTG, HIV, Hep ABCE, TFTs, EBV viral load. EBV, CMV IgG +ve. CMV titres 696 c/ml June 2023. CD 19 undetectable. IgG4 0.02 g/L. MPO, PR3 negative. BK virus was detected in urine. There was no sustained response to iv methylprednisolone and a course of filgotinib given for possible systemic RA symptoms. She developed a dry cough and shortness of breath. PET-CT July 2023 - bilateral FDG avid large confluent areas of consolidation. Urine + bronchial washings were negative for TB growth at 42 days. However, in view of deterioration empirical TB treatment was started July 2023. CT urogram in September 2023 showed likely bilateral renal abcesses, as well as bilateral hydronephrosis. Left renal cyst aspirate was performed and empirical doxycycline started at 100 mg bd. Ureaplasma detected from the aspirate on PCR. 3 weeks doxycyline given with rapid resolution of fevers and CRP. February 2024- cystectomy and ileal conduit in for refractory interstitial cystitis with a poorly compliant, small capacity, thick walled fibrotic bladder which had caused bilateral ureteric obstruction. She has made a good recovery. TB treatment course was completed. Discussion This case shows the difficulties in diagnosing infection from a little known and difficult to detect organism, ureaplasma. Discovered in the 1950s, it has no cell wall and very small genome and is therefore an obligate parasite /saprophyte. Together with mycoplasma it belongs to the bacterial class of Mollicutes. It cannot be routinely cultured nor gram stained. PCR or specialist culture is required. It may be present as a commensal but has been implicated in symptomatic genitourinary infections. It has also been implicated in native and non-native joint infections, and in infants can cause a pneumonic illness. Empirical treatment may be indicated due to long turn around times for diagnosis. There is some evidence that reduced humoral immunity may be a contributory factor to infection. We have found a previous case described of ureaplasma renal abcesses in a patient with MS and neurogenic bladder treated with rituximab. Our patient had normal immunoglobulin levels though still had profound CD19 suppression. Further immune suppression resulted from methylprednisolone and course of filgotinib, which may have accelerated the course of infection. Ureaplasma and mycoplasma do not have a cell wall, thus making beta-lactam antibiotics and vancomycin ineffective. Cyclines, josamycin and fluroquinolones are effective, though there is increasing resistance developing. We gave a relatively long course of doxycycline as our patient was very unwell and had apparent extensive urinary tract involvement. BK virus seropositivity is present in 90% of the normal population and asymptomatic viruria in up to 20%. However, it is a cause of renal tract inflammation in the immunosuppressed – in particular post-transplant. We felt it was unlikely to be significant in our patient in view of the clinical picture, lack of BK viraemia and negative viral findings on bladder biopsy. Key learning points • Ureaplasma should be on the list of organisms to consider in cases of PUO when the more common infective causes have been ruled out, particularly in immune suppressed patients. Patience and close collaboration with colleagues is essential. This patient had multiple MDT meetings involving infectious disease, respiratory, secondary and tertiary care urology and rheumatology specialists. The collaboration was invaluable. A course of doxycycline may be considered as a relatively low risk approach while awaiting microbiological confirmation in such cases.

P17 Infectious sacroiliitis: an uncommon septic arthritis

Abstract Introduction Infectious sacroiliitis, an infection of the sacroiliac joint, can cause severe morbidity if not promptly treated. Staphylococcus aureus is a common pathogen, especially problematic in patients on chronic hydrocortisone therapy due to its immunosuppressive effects. This case report discusses the diagnosis and treatment challenges of infectious sacroiliitis in such immunocompromised patients, highlighting the necessity of a minimum six-week targeted antibiotic regimen to ensure bacterial eradication and prevent relapse. The report emphasises aggressive and sustained treatment for optimal outcomes in these vulnerable patients. Case description A 47-year-old man was admitted with fever, constant feeling of tiredness, and severe right-sided gluteal pain radiating to the right lower extremity, worsening with movement. He has a history of ACTH deficiency, managed with 25 mg of oral hydrocortisone daily. Examination revealed skin eczema, tenderness in the right gluteal region, and an inability to flex the right hip. His temperature was 39 °C, and CRP levels were over 400 mg/L (normal < 5 mg/L). Two sets of blood cultures showed Staphylococcus aureus. Echocardiogram ruled out of infective endocarditis. An MRI of the lumbar spine showed edema in the right posterior paraspinal muscles at L4, while a CT scan of the abdomen and pelvis revealed fat stranding around the second sacral vertebra and significant inflammation in the right iliacus and distal psoas muscles. The patient was treated with 21 days of intravenous flucloxacillin, resulting in negative blood cultures and improved inflammatory markers, leading to discharge. One week later, he was readmitted with severe gluteal pain and fever. Blood cultures again showed Staphylococcus aureus. A repeat MRI indicated an abnormal signal around the right sacroiliac (SI) joint, with extensive edema and swelling in the right gluteal, iliacus, posterior paraspinal, and obturator muscles, suggesting sacroiliitis. The patient received six weeks of intravenous flucloxacillin. After this extended antibiotic therapy, his pain and fever resolved, laboratory parameters normalised, and blood cultures were negative. Discussion Bacterial infection is a serious cause of arthritis, with infective sacroiliitis being particularly rare, accounting for just 1-2% of all septic arthritis cases. Diagnosing this condition can be challenging despite clear symptoms, often leading to delays. This case highlights several important aspects of managing severe musculoskeletal infections. Firstly, it emphasises the need for a comprehensive diagnostic approach, utilising blood cultures, imaging, and echocardiography to precisely identify the source and extent of the infection. Treating deep-seated musculoskeletal infections is especially challenging in patients with underlying conditions which can complicate the clinical picture and impact immune response. The recurrence of infection despite initial appropriate antibiotic therapy suggests the need for prolonged and potentially more aggressive antimicrobial treatment. Close monitoring for complications or recurrence is essential. The decision to restart IV flucloxacillin and extend the antibiotic course to at least six weeks represents a strategic adjustment based on clinical progression and imaging results. Given that the patient is currently on standard hydrocortisone therapy for ACTH deficiency, transitioning to modified-release hydrocortisone therapy may be a better option as it more closely mimics the circadian rhythm of glucocorticoids, normalises the immune cell profile, and reduces the incidence of recurrent infections. This case underscores the necessity for clinicians to remain vigilant for recurrent infections, considering extended or repeated imaging and microbiological studies in patients not responding as expected to initial therapy. It also highlights the importance of individualised treatment plans, especially for patients with complex medical histories and comorbidities, to achieve optimal clinical outcomes. Key learning points • Diagnostic challenges: Infectious sacroiliitis is rare and difficult to diagnose, requiring comprehensive approaches including blood cultures, imaging and echocardiography. • Immunocompromised patients: Patients on chronic hydrocortisone therapy are at higher risk for infections like sacroiliitis due to immunosuppression. Modified hydrocortisone may represent a superior option, as it more closely mimics the physiological circadian rhythm of glucocorticoids, normalises the immune cell profile, and reduces the incidence of recurrent infections. • Rare disease: Infectious sacroiliitis is a rare and often overlooked condition that requires a high index of suspicion for accurate diagnosis. Early recognition and prompt treatment are crucial to prevent serious complications and improve patient outcomes. • Prolonged treatment: Initial antibiotic therapy may lead to temporary improvement, but extended antimicrobial regimens (at least six weeks) are often necessary to prevent relapse. • Relapse management: The recurrent of symptoms and positive cultures necessitates vigilant monitoring and possibly more aggressive and prolonged antibiotic treatment. • Individualised care: Effective management of deep-seated infections in patients with complex medical histories requires tailored treatment plans and ongoing assessment to achieve optimal outcomes.

Predictors of Successful Antibiotic Treatment of Osteomyelitis in Diabetic Forefoot Infection.

Osteomyelitis (OM) associated with diabetic foot ulceration (DFU) is a growing public health challenge worldwide. Since 2012 the number of patients presenting with DFU per year to our centre has doubled. This study aims to evaluate outcomes from outpatient antibiotic therapy (OPAT) in the management of OM in DFU patients. A retrospective analysis was performed of medical notes, radiology, and vascular laboratory reports for all DFU patients with OM treated from April 2016 to April 2020. Variables analyzed included age, gender, site of OM, WIfI Score (Wound Ischaemia and foot Infection Score), probe-to-bone test (PTB), imaging (X-ray/magnetic resonance imaging (MRI), co-morbidities (peripheral arterial disease (PAD), chronic kidney disease (CKD), hypertension (HTN), smoking, ischemic heart disease (IHD), and dyslipidaemia. Outcomes evaluated were healing, recurrent DFU, and freedom from amputation at 12months. 185 patients were admitted with 264 infected digits (Male 223; Female 41). The mean age was 66years. Only 168 (63.6%) were fully healed at 12months. Of the 96 patients who failed to heal, 43 underwent a repeat course of prolonged antibiotics without improvement. Factors associated with treatment failure were PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene. Extended outpatient antibiotic therapy (with an inpatient multidisciplinary approach) is an effective treatment for digital OM in DFU with a success rate of 63%. In recurrence, repeating prolonged antibiotics is unlikely to achieve healing. PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene are predictors of treatment failure.

Gut Microbiome in Human Melioidosis: Composition and Resistome Dynamics from Diagnosis to Discovery

Abstract Background Melioidosis, attributable to the soil-dwelling bacterium Burkholderia pseudomallei, stands as a paramount global health challenge, necessitating extended courses of antibiotics. While murine studies identified the gut microbiota as a modulator of bacterial dissemination during melioidosis, the human intestinal microbiota during melioidosis remains uncharacterized. Here, we characterized gut microbiota composition and antimicrobial resistance (AMR) genes at diagnosis, during treatment, and postdischarge for melioidosis. We hypothesized that the gut microbiota of melioidosis patients would be extensively distorted. Methods In this prospective observational cohort, stool samples of patients with culture-confirmed melioidosis admitted to a tertiary care hospital in India were collected at diagnosis, 14 days after diagnosis, or discharge (whichever occurred first) and at 6 months postinfection. Family members or neighbors served as community controls. The gut microbiota and resistome were profiled by shotgun metagenomic sequencing. Results We longitudinally analyzed the gut microbiota of 70 fecal samples from 28 patients and 16 community controls. At diagnosis, the gut microbiota of patients differed from that of controls, characterized by high abundances of potentially pathogenic bacteria, a loss of butyrate-producing bacteria, and higher levels of AMR genes. Microbiota composition and resistome remained different from community controls at 6 months, driven by total antibiotic exposure. During hospitalization, gut microbiota profiles were associated with secondary Klebsiella pneumoniae infections. Conclusions This first study on gut microbiota composition and resistome in human melioidosis showed extensive disruptions during hospitalization, with limited signs of restoration 6 months postinfection. Given the adverse outcomes linked with microbiome perturbations, limiting microbiota disruptions or using microbiota-restorative therapies (eg, butyrate-producing probiotics) may be beneficial.

COVID-19 and COVID-19 Vaccine-Related Skin Ulcerations in the Lower Extremities: A Case Report and Literature Review

Several associations have been made between COVID-19 and vasculitis. Recent data also shows the prevalence and association of de novo vasculitis with either COVID-19 infection or COVID-19 post vaccination. In this article, we present the case of new-onset leukocytoclastic vasculitis, secondary to COVID-19 vaccination, that was complicated by severe infected and nonhealing ulcers in the lower extremities. Case A 53-year-old male patient presented to the dermatology clinics with a three-week history of painful necrotic patches coalescent of the lateral malleolus of the right and left ankles. History goes back to when the patient reported developing pruritic papules two weeks after receiving his second shot of the Pfizer BioNTech COVID-19 vaccine (BNT162b2). Punch biopsy was consistent with leukocytoclastic vasculitis. He was prescribed a four-week course of systemic corticosteroids and antibiotics as per cultures. Vascular assessment confirmed normal peripheral arterial and venous system. Two months later, the patient re-presented with fever and worsening of his lower extremity ulcers. He underwent debridement of his wounds. Intra-operative cultures revealed multidrug resistant bacteria. He required an additional debridement session a few days later and a 14-day course of Piperacillin-Tazobactam. The patient was subsequently discharged on corticosteroids and Azathioprine and followed up in the vascular surgery and rheumatology clinics. At four months follow-up, the patient's wounds were almost completely healed. Conclusion This article highlights a case of severe new-onset COVID-19 vaccine-associated leukocytoclastic vasculitis complicated with infected ulcers that required debridement twice in addition to a prolonged course of antibiotics and immunosuppression therapy. To our knowledge, none of the cases reported in the literature were this severe in nature. In this post-pandemic era, it must remain high on the differential list, and healthcare specialists should maintain a high index of suspicion when evaluating sudden new-onset skin lesions that do not have an immediately apparent etiology.

Novel CYCLIN-O pathogenic variants in a patient presenting with bronchiectasis secondary to reduced generation of multiple motile cilia.

Reduced generation of multiple motile cilia (RGMC) represents a rare variant of Primary Ciliary Dyskinesia (PCD), associated with CYCLIN-O (CCNO) mutations. We report a novel compound mutation in the CCNO gene in an adult Chinese Singaporean exhibiting chronic productive cough since childhood and recurrent sino-pulmonary infections. Low nasal nitric oxide and bronchiectasis suggests PCD. Bronchoscopy for epithelial and nasal brushings for ciliary studies were repeated after adequate treatment of lower respiratory tract infections. Demonstration of oligo-cilia via transmission electron microscopy, and detection of CCNO mutation through genetic analysis were utilized to diagnose RGMC. Repeated courses of antibiotics including nebulised antibiotics were used to treat recurrent infections and exacerbations. Airway clearance techniques, immunizations and collaboration with otorhinolaryngologist form part of the long-term management. Heightened clinical suspicion and adherence to established diagnostic algorithms are essential for timely recognition of this entity.

Lesion-like effect of gliosis secondary to deep brain stimulation electrode infection: illustrative case.

Deep brain stimulation (DBS) is commonly used to treat Parkinson's disease (PD) and other movement disorders when other treatments fail. Although DBS can significantly improve motor symptoms, it carries risks such as infections, which can require multiple surgeries and prolonged antibiotic therapy. Research on the long-term neurological effects of DBS-related infections is limited. A 58-year-old man with a 13-year history of PD, refractory to optimized clinical management, underwent subthalamic nucleus (STN) DBS after previous contralateral lesioning of the posterior subthalamic area. Postoperatively, the DBS lead migrated upward and was repositioned, but he developed perielectrode cerebritis 5 days later. The DBS system was completely removed, and he underwent a 28-day course of intravenous antibiotics. Initially, his motor symptoms remained unchanged, but 4 months later, he experienced a significant and sustained motor symptom improvement that continued until the last follow-up assessment (40 months). Magnetic resonance imaging performed 2 years after the explantation showed gliosis and hemosiderin deposition in the STN, suggesting that the infection-induced gliosis had a lesion-like effect, leading to the observed clinical improvement. This case suggests that infection-induced gliosis from DBS complications can unexpectedly result in long-term motor symptom improvements, potentially influencing future management strategies for similar cases. https://thejns.org/doi/10.3171/CASE24502.

Early-Life Infections, Antibiotics and Later Risk of Childhood and Early Adult-Onset Inflammatory Bowel Disease: Pooled Analysis of Two Scandinavian Birth Cohorts.

Childhood antibiotic use has been associated with inflammatory bowel disease (IBD), although the potential contribution of infection frequency remains uncertain. To explore the association between early-life infections, antibiotics and IBD development. We used population-based data from ABIS (Sweden) and MoBa (Norway) cohorts following children from birth (1997-2009) until 2021. Prospectively collected questionnaires identified infection frequency (any, gastrointestinal and respiratory) and antibiotics (any, penicillin and non-penicillin) until age 3. IBD diagnosis required ≥ 2 records in national health registries. Cohort-specific hazard ratios (aHR), adjusted for parental education, smoking and IBD were estimated and pooled using a random-effects model. Antibiotic analyses were adjusted for infection frequency. There were 103,046 children (11,872 ABIS and 91,174 MoBa), contributing to 1,663,898 person-years of follow-up, during which 395 were diagnosed with IBD. The frequency of any infection at 0 to < 1 and 1 to < 3 years showed a pooled aHR of 1.01 (95% confidence interval [CI] = 0.96-1.07) and 1.00 (95% CI = 0.99-1.01) per additional infection for IBD. Adjusting for infections, any versus no antibiotics in the first year was associated with IBD (pooled aHR = 1.33 [95% CI = 1.01-1.76]). The aHR for additional antibiotic course was 1.17 (95% CI = 0.96-1.44), driven by penicillin (per additional course, aHR = 1.28 [95% CI = 1.02-1.60]). Although antibiotics at 1 to < 3 years did not show an association with IBD or Crohn's disease, non-penicillin antibiotics were associated with ulcerative colitis (per additional course, aHR = 1.95 [95% CI = 1.38-2.75]). Early-life antibiotic use was, a significant risk factor for childhood and early adult-onset IBD, independent of infection frequency.

Can "LITE" Procedure Combined With a Short Course Antibiotic Treatment Be Effective in Treating the Chronic PJI?-A Prospective Randomized Controlled Trial.

The prevailing treatment for chronic periprosthetic joint infection (PJI) is a two-stage exchange, yet the optimal duration of antibiotic therapy following this procedure remains a topic of debate. This study aimed to determine whether a short course of postoperative antibiotic therapy can maintain infection control rates following a long interval two-stage exchange (LITE) for PJI. We conducted a prospective study enrolling patients with chronic PJI who underwent the LITE procedure at our institution from April 2018 to November 2021. Patients were randomly assigned to receive either a long course (12 weeks) or short course (2 weeks) of postoperative antibiotics. The pathogens, antibiotics, inflammatory markers, antibiotic-related complications, cases of reinfection, or re-operation were recorded. Continuous variables were analyzed using the two-sample t-test or Mann-Whitney U test, and categorical variables were analyzed using Fisher's exact tests. Kaplan-Meier survival analysis was used to compare infection control rates. A total of 60 patients with chronic PJI who completed the LITE procedure were included in the study (30 patients per group). All patients were followed for a minimum of 24 months (mean 39.2 ± 13.0 months). We observed that the infection control rate in the short-course group was not inferior to that in the long-course group (96.7% vs. 96.7%, p = 1.000). For patients with chronic PJI undergoing the LITE procedure, a 2-week course of postoperative antibiotics suffices to maintain infection control rates. Chinese Clinical Trial Registry: ChiCTR1900027089.

Knowledge and Attitude of self-medication with leftover antibiotics in Saudi Arabia: A cross-sectional study

Background Antimicrobial resistance is increasing at an alarming rate. The use of antibiotics without a prescription by a patient or other family members and their inappropriate storage have caused serious health issues as it would lead to antibiotic resistance and exposure to the risk of harmful adverse effects unnecessarily. Therefore, the study aimed to evaluate the current behaviour of antibiotic usage, storage, re-usage and misuse among the residents of Saudi Arabia. Methods This is a cross-sectional study. Our target study population was the residents of Saudi Arabia. Data were collected by an online questionnaire and analysed by SPSS. Results A total of 738 participants answered the online questionnaire from all ages, genders, nationalities, and socioeconomic backgrounds residing in different regions across the Kingdom of Saudi Arabia. 76.42% knew that an antibiotic is a chemical substance used to treat infections. The participants were questioned about when they started using antibiotics, to which 95.66% (n=706) responded after consulting a physician, 3.25% (n=24) said when they felt ill for any reason, and 1.08% (n=8) replied after first attempting herbal medicine. A total of 147 participants admitted that they store excess pills of antibiotics after being prescribed for an infection and reuse them later on for symptoms like sore throat and fever. Conclusions The results indicated that nearly half of the participants used leftover antibiotics. Participants having children in their homes significantly reuse antibiotics. However, one-third of the participants didn’t complete the antibiotics course. A large portion of the population, regardless of age, level of education, or professional background, have continued to store leftover antibiotics after an infection treatment and reuse them once they think they need them for new symptoms. This advice further revises the current measures to fill those gaps and reduce this habit.