Intravenous Antimicrobial Therapy Research Articles

Comparison of oral versus intravenous antimicrobial therapy for patients who were diagnosed with bloodstream infections due to Gram-negative bacilli after discharge from the emergency department: A retrospective analysis

IntroductionInfections caused by Gram-negative bacilli (GNB) in the emergency department (ED) are common, and the blood cultures taken at the visit can turn positive often after the discharge. However, the differences in the clinical outcomes depending on the subsequent decision-making, either to giving the patients intravenous or oral antibiotics remain unknown. MethodsA single-center retrospective observational study was conducted for the outcome of the patients whose blood cultures at the visit turned positive and detected GNB. The primary outcomes were 30- and 90-day all-cause mortality from the first positive blood cultures, comparing intravenous treatment (IVT) and oral treatment (OT). The propensity score analysis was used to adjust potential confounders. ResultsA total of 283 patients with GNB bloodstream infections (BSIs) diagnosed after ED discharge. No death occurred in either group within 30 days, with the average treatment effect (ATE) of OT being <0.001 (p = 0.45) after inverse probability weighting (IPW). At 90 days, mortality was 2.5 % for the OT group and 0 % for the IVT group (ATE 0.051; 96%CI 0.013–0.098; p = 0.001). ConclusionAll of patients treated with oral antibiotics were alive at 30 days, but had a higher 90-day mortality compared to those given intravenous agents. The results were consistent after adjusting the potential confounders by using IPW. Given the overall low mortality in both groups after 90 days, even though oral antibiotic therapy was associated with higher mortality statistically, one might consider this as an option especially when the patient's preference was compelling.

Exogenous Glucose Interferes with Antimicrobial-Mediated ROS Accumulation and Bacterial Death.

Glucose is widely used in the reconstitution of intravenous medications, which often include antimicrobials. How glucose affects antimicrobial activity has not been comprehensively studied. The present work reports that glucose added to bacteria growing in a rich medium suppresses the bactericidal but not the bacteriostatic activity of several antimicrobial classes, thereby revealing a phenomenon called glucose-mediated antimicrobial tolerance. Glucose, at concentrations corresponding to blood-sugar levels of humans, increased survival of Escherichia coli treated with quinolones, aminoglycosides, and cephalosporins with little effect on minimal inhibitory concentration. Glucose suppressed a ROS surge stimulated by ciprofloxacin. Genes involved in phosphorylated fructose metabolism contributed to glucose-mediated tolerance, since a pfkA deficiency, which blocks the formation of fructose-1,6-bisphosphate, eliminated protection by glucose. Disrupting the pentose phosphate pathway or the TCA cycle failed to alter glucose-mediated tolerance, consistent with an upstream involvement of phosphorylated fructose. Exogenous sodium pyruvate or sodium citrate reversed glucose-mediated antimicrobial tolerance. Both metabolites bypass the effects of fructose-1,6-bisphosphate, a compound known to scavenge hydroxyl radical and chelate iron, activities that suppress ROS accumulation. Treatment with these two compounds constitutes a novel way to mitigate the glucose-mediated antimicrobial tolerance that may exist during intravenous antimicrobial therapy, especially for diabetes patients.

The Diagnosis and Treatment of Acute Cholecystitis: A Comprehensive Narrative Review for a Practical Approach.

Acute cholecystitis (AC), generally associated with the presence of gallstones, is a relatively frequent disease that can lead to serious complications. For these reasons, AC warrants prompt clinical diagnosis and management. There is general agreement in terms of considering early laparoscopic cholecystectomy (ELC) to be the best treatment for AC. The optimal timeframe to perform ELC is within 72 h from diagnosis, with a possible extension of up to 7-10 days from symptom onset. In the first hours or days after hospital admission, before an ELC procedure, the patient's medical management comprises fasting, intravenous fluid infusion, antimicrobial therapy, and possible administration of analgesics. Additionally, concomitant conditions such as choledocholithiasis, cholangitis, biliary pancreatitis, or systemic complications must be recognized and adequately treated. The importance of ELC is related to the frequent recurrence of symptoms and complications of gallstone disease in the interval period between the onset of AC and surgical intervention. In patients who are not eligible for ELC, it is suggested to delay surgery at least 6 weeks after the clinical presentation. Critically ill patients, who are unfit for surgery, may require rescue treatments, such as percutaneous or endoscopic gallbladder drainage (GBD). A particular treatment approach should be applied to special populations such as pregnant women, cirrhotic, and elderly patients. In this review, we provide a practical diagnostic and therapeutic approach to AC, even in specific clinical situations, based on evidence from the literature.

Periportal Edema as an Extrarenal Manifestation of Acute Pyelonephritis.

Acute pyelonephritis is a common infection of the upper urinary tract that affects approximately 250,000 adults in the United States. Individuals with acute pyelonephritis require hospitalization and intravenous antimicrobial therapy. Diagnoses of acute pyelonephritis are made on the basis of clinical and laboratory findings. Individuals with complex or severe acute pyelonephritis undergo contrast-enhanced computed tomography (CT) for the diagnosis and assessment of perirenal abnormalities. However, extrarenal manifestations, such as periportal edema and gallbladder wall thickening, may complicate the diagnostic process. We report the case of a 42-year-old woman who presented with fever, dysuria, and flank pain-the hallmarks of urosepsis. CT results confirmed acute pyelonephritis accompanied by periportal edema and elevated levels of hepatic enzymes and C-reactive protein. Despite antibiotic intervention, febrile episodes persisted for 4 days and abated over a fortnight. The patient's blood and urine cultures yielded negative results, which may be attributed to her prior antimicrobial treatment. Recognition of extrarenal signs in acute pyelonephritis is crucial for obtaining accurate diagnoses and understanding their clinical implications.

Dalbavancina como tratamiento antibiótico de consolidación en endocarditis infecciosa, infección de dispositivos de estimulación cardiaca y bacteriemia: experiencia clínica de 7 años

IntroductionDalbavancin (DBV), a novel lipoglycopeptide with activity against Gram-positive bacterial infections, is approved for the treatment of acute bacterial skin and skin structure infections. It has linear dose-related pharmacokinetics allowing a prolonged interval between doses. It would be a good option for the treatment of patients with Gram-positive cardiovascular infections. Material and methodsRetrospective analysis of patients with cardiovascular infection (bacteremia, implantable electronic device infection and infective endocarditis [IE]) treated with DBV at Hospital Clínico San Carlos (Madrid) for 7 years (2016-2022). Patients were divided into 2 study groups: 1) IE, and 2) bacteremia. Epidemiological, clinical, microbiological and therapeutic data were analyzed. ResultsA total of 25 patients were treated with DBV for cardiovascular infection. IE was the most common indication (68%), followed by bacteremia (32%) with male predominance in both groups (64 vs. 62%) and median age of 67,7 and 57,5 years, respectively. Hundred percent of blood cultures were positive to Gram-positive microorganisms (Staphylococcus spp., Streptococcus spp. or Enterococcus spp.) in both study groups. Previously to DBV, all patients received other antibiotic therapy, both in the group of IE (median: 80 days) as in bacteremia (14,8 days). The main reason for the administration of DBV was to continue intravenous antimicrobial therapy outside the hospital in both the EI group (n=15) and the bacteremia group (n=8). DBV was used as consolidation therapy in a once- or twice-weekly regimen. Microbiological and clinical successes were reached in 84% of cases (n=21), 76,4% in IE group and 100% in bacteremia group. No patient documented adverse effects during long-term DBV treatment. ConclusionDBV is an effective and safety treatment as consolidation antibiotic therapy in IE and bacteremia produced by Gram-positive microorganisms.

Cefoxitin for Intra-amniotic Infections and Endometritis: A Retrospective Comparison to Traditional Antimicrobial Therapy Regimens Within a Healthcare System.

Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change. This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling. A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio, .37; 95% CI, .17-.76; P = .010). Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI.

Pediatric Outpatient Parenteral Antimicrobial Therapy (OPAT): Experience of Families During Implementation of the Program

Abstract Background Experience with ambulatory intravenous antimicrobial therapy in pediatrics is reported since 1973. This modality avoids hospitalization or helps for early discharge in a patient who, in addition to antibiotics, has no other criteria to remain hospitalized. Even though it reduces the risks and costs that hospitalization entails and allows the patient to remain inserted in his family its use is not widespread in Latin America. We report the experience of families during the implementation of outpatient parenteral antibiotic therapy (OPAT) in pediatric oncologic patients at Solca Guayaquil. Methods A pilot program for outpatient parenteral antibiotic therapy (OPAT) was started in March 2022. We included patients with a permanent central venous access (port-a-cath) who were otherwise clinical stable (afebrile &amp;gt; 48h, increasing absolute neutrophil count (&amp;gt;500 in hematologic malignancies, &amp;gt;100 in solid tumors), no transfusion requirement) and completed a social questionnaire described previously (SUAU C, Thelma et al) with a score &amp;gt; 9. Patients had follow up with pediatric infectious diseases once a week during therapy and received a certificate of completion on their last day with a QR code to complete an anonymous online survey regarding their experience with the program. Results From March to November 2022 there were 6 patients enrolled. Their mean age 9.6 years, 3 (50%) were male and mean duration of therapy 7.7 days. Response rate was 100%. Ronald Mc. Donald's house hosted 5 (83%) patients while 1 (17%) was staying at home. There was 1 (16.7%) readmission 72h after completion of the program. No disfunction of catheter, secondary infection or deaths were reported. Return to regular activities was possible for 4 (67%) of patients. The experience was considered excellent, good or average in 3(50%), 2(33%) and 1(17%) cases. Quality of care during OPAT was perceived as exceeding expectations, meeting expectations and no opinion in 2(33%), 3(50%), and 1(17%) respectively. Support received by hospital staff was pondered excellent and good in 3 (50%) each. All of the patients agreed that OPAT was better than staying admitted however 1 (17%) declared that would not take this modality again (referred as "stressful"). Conclusion The newly implemented OPAT program was perceived overall as a positive experience for patients and their families, there were no major complications. The feedback provided helped to improve the logistics of the program.

Real-World Usage of Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% in Patients with Multiple Myeloma Diagnosed with Secondary Immunodeficiency Disease

Introduction: In patients with mature B-cell malignancies such as multiple myeloma (MM), both the underlying disease and immunosuppressive therapy can result in patients developing secondary immunodeficiency disease (SID). SID often manifests in severe, recurrent, or persistent infections that can impair a patient's quality of life and are a major cause of morbidity and mortality in patients with MM, thereby resulting in significant clinical and socioeconomic burden. The use of immunoglobulin (Ig) replacement therapy is well established for the treatment of hypogammaglobulinemia in patients with primary immunodeficiency disease (PIDD). Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% is a dual-vial unit of IgG 10% and recombinant human hyaluronidase (rHuPH20). fSCIG 10% is approved in the USA for the treatment of adults and children aged 2 years or older with PIDD, and in the EU for adults and children of any age with PIDD or SID. fSCIG 10% is not fully integrated into standard of care for patients with SID in many countries, in part owing to comparatively less familiarity of hematologists and oncologists with the evidence supporting the use of fSCIG 10% than for intravenous IgG therapy in patients with SID. Therefore, the HyMMy study (NCT05879757) aims to generate real-world evidence to gain a better understanding of patterns of fSCIG 10% use and outcomes in patients with MM and SID. Methods: HyMMy is a prospective, noninterventional, observational study that will be conducted at 30 centers in Europe and South America. It is planned for 100 patients to be enrolled and observed over a 12-month follow-up period. The overall duration of the study will be 38 months. Patients will be eligible for inclusion if they are aged 18 years or older, have a diagnosis of MM, and fulfill the diagnosis criteria for SID: patient suffers from severe, recurrent, or persistent infection despite appropriate anti-infective treatment, and has proven specific antibody failure or a serum IgG trough level of less than 4 g/L (excluding paraprotein). Patients may enter the study after being diagnosed with SID and no more than 30 days after fSCIG 10% treatment initiation, or with no more than 2 doses of fSCIG 10% already infused ( Figure). Patients newly starting fSCIG 10% have a 30-day window from enrollment to inclusion. Patients will be excluded if they have PIDD, have received Ig treatment or prophylaxis within 3 months of enrollment, have an ongoing serious infection requiring intravenous antimicrobial therapy, have a history of malignancy other than MM within 3 years of enrollment, or have had major surgery within 2 weeks of enrollment. The primary endpoint is to characterize the real-world infusion parameters of fSCIG 10% administration (dosing and administration characteristics; treatment interval; infusion volume, sites, rate, and duration; training visits; and fSCIG 10% discontinuation, interruption, or switch to other treatment). Secondary endpoints will examine the disease course and clinical management of MM (including overall survival and healthcare resource utilization) in patients treated with fSCIG 10%. The exploratory endpoints include: burden of infection; infection rate, type, duration, and severity; patient-reported outcomes pertaining to health-related quality of life, collected via questionnaire at the patients' visit; and overall physician assessment of fSCIG 10% utilization, tolerability, and effectiveness, as measured by a 5-point Likert scale questionnaire. Results: Patient recruitment started in June 2023. Interim analysis is planned after enrollment of the first 50 patients, and the estimated end of the study is 2026. Conclusions: HyMMy is the first prospective, observational study that focuses on the assessment of fSCIG 10% utilization patterns in adults with MM diagnosed with SID. The study will help to improve understanding of the treatment patterns and options available for patients with SID and hematologic malignancies, in particular MM. Takeda Development Center Americas, Inc. funded this study. Takeda Pharmaceuticals International AG funded writing support.

Brucellar, Pyogenic, and Tuberculous Spondylodiscitis at Tertiary Hospitals in Saudi Arabia: A Comparative Retrospective Cohort Study.

Spondylodiscitis is rare yet the most common form of spinal infection. It is characterized by inflammation of the intervertebral disk space and adjacent vertebral body. In Western countries, the incidence of spondylodiscitis is increasing. Clinical outcomes most commonly reported in the literature are the 1-year mortality rate (range, 6%-12%) and neurologic deficits. This multicenter retrospective cohort study assessed patients diagnosed with infectious spondylodiscitis who received treatment at King Abdulaziz Medical City in Riyadh and Jeddah, Saudi Arabia. All enrolled patients were ≥18 years old and were diagnosed per radiologic and microbiological findings and clinical manifestations between January 2017 and November 2021. This study enrolled 76 patients with infectious spondylodiscitis, with a median age of 61 years. All patients presented with back pain for a median 30 days. Patients were stratified into 3 groups based on the causative pathogen: brucellar spondylodiscitis (n = 52), tuberculous spondylodiscitis (n = 13), and pyogenic spondylodiscitis (n = 11). All laboratory data and biochemical markers were not significantly different. However, C-reactive protein, erythrocyte sedimentation rate, and white blood cells were significantly different in the pyogenic spondylodiscitis group, with medians of 121 mg/dL (P = .03), 82 mmol/h (P = .04), and 11.2 × 109/L (P = .014), respectively. Back pain is a common clinical feature associated with infectious spondylodiscitis. The immense value of microbiological investigations accompanied with histologic studies in determining the causative pathogen cannot be emphasized enough. Treatment with prolonged intravenous antimicrobial therapy with surgical intervention in some cases produced a cure rate exceeding 60%.

Low Vitamin C Concentrations in Patients with Community-Acquired Pneumonia Resolved with Pragmatic Administration of Intravenous and Oral Vitamin C.

Community-acquired pneumonia (CAP) is characterized by elevated markers of inflammation and oxidative stress and depleted circulating concentrations of the antioxidant nutrient vitamin C. A feasibility trial of intravenous and oral vitamin C supplementation, matched to the timing of intravenous and oral antibiotic formulations, was carried out and changes in vitamin C status were monitored to determine whether saturating status could be achieved throughout the administration period. Patients with moderate and severe CAP (CURB-65 ≥ 2; n = 75) who were receiving intravenous antimicrobial therapy were randomized to placebo (n = 39) or intravenous vitamin C (2.5 g per 8 h; n = 36) before moving to oral vitamin C (1 g three times daily) when prescribed oral antimicrobials. Blood samples were collected at baseline and then daily whilst in the hospital. Vitamin C concentrations were determined by high-performance liquid chromatography. The inflammatory and infection biomarkers C-reactive protein and procalcitonin were elevated at baseline (158 (61, 277) mg/L and 414 (155, 1708) ng/L, respectively), and vitamin C concentrations were depleted (15 (7, 25) µmol/L). There was an inverse association between vitamin C and C-reactive protein concentrations (r = -0.312, p = 0.01). Within one day of intervention initiation, plasma vitamin C concentrations in the vitamin C group reached median concentrations of 227 (109, 422) µmol/L, and circulating concentrations remained at ≥150 µmol/L for the duration of the intervention, whilst median vitamin C concentrations in the placebo group remained low (≤35 µmol/L). There was a trend toward decreased duration of hospital stay (p = 0.07) and time to clinical stability (p = 0.08) in the vitamin C group. In conclusion, patients with moderate to severe CAP have inadequate plasma vitamin C concentrations for the duration of their hospital stay. The administration of intravenous or oral vitamin C, titrated to match the antimicrobial formulation, provided saturating plasma vitamin C concentrations whilst in the hospital. There were trends toward shorter duration of hospital stay and time to clinical stability. Thus, larger trials assessing the impact of intravenous and oral vitamin C intervention on CAP clinical outcomes are indicated.

Lumbar spine epidural abscess and facet joint septic arthritis in a pediatric patient.

A 13-year-old girl presented with lower back pain that began 7 days earlier after a volleyball workout. She had no history of trauma or fever. On physical examination, a contraction of the left paravertebral muscles associated with pain on flexion-extension of the spine and a positive left Lasègue's sign were evident. She had no neurological deficits in the lower limbs. Chest and lumbosacral X-rays were unremarkable, and a laboratory investigation revealed neutrophilia and elevated C-reactive protein (75.7 mg/L; normal value < 5). Urine and blood cultures were carried out before starting ceftriaxone. She developed a fever (38.8 °C) 1 day after admission, and the blood culture was positive for methicillin-sensitive Staphylococcus aureus. A lumbosacral magnetic resonance imaging (MRI) scan was performed considering the clinical and microbiological evidence and suspecting an osteoarticular infection. The MRI revealed a small amount of interarticular fluid in the left L4-L5 hemivertebral region and a posterior spinal epidural abscess on the left side extending from L4 to L5-S1 (Fig. 1). The diagnosis was lumbar spine epidural abscess (SEA) and facet joint septic arthritis (SAFJ). As the girl did not present with neurological symptoms, no surgical treatment was indicated, and cefazolin was administered intravenously with rapid resolution of the fever and pain. She was discharged after 4 weeks of intravenous antimicrobial therapy, which was followed by 4 more weeks of oral antibiotic therapy with levofloxacin. The 3-month follow-up MRI showed complete regression of the epidural fluid and almost complete normalization of the signal abnormalities in the L4-L5 soft tissues (Fig. S1). Facet joint septic arthritis is a rare condition.1Mas-Atance J. Gil-García M.I. Jover-Sáenz A. Curià-Jové E. Jové-Talavera R. Charlez-Marco A. et al.Septi carthritis of a posteriorlumbarfacet joint in an infant: a case report.Spine (Phila Pa 1976). 2009; 34: E465-E468Crossref PubMed Scopus (10) Google Scholar Few pediatric cases have been described, mainly in immunosuppressed patients. The most commonly associated pathogen is S. aureus.2Cabet S. Perge K. Ouziel A. Vandergugten S. Guibaud L. Ferry T. et al.Septic arthritis of facet joint in children: a systematic review and a 10-year consecutive case series.Pediatr Infect Dis J. 2021; 40: 411-417Crossref PubMed Scopus (0) Google Scholar The mechanism of the spread of this infection is not understood, but contamination may originate from direct inoculation, contiguity, or hematogenous dissemination. In the present case, the patient had no history of lumbar or epidural injections, so the most likely origin was hematogenous dissemination. The coexistence of localized epidural, articular, and paravertebral abnormalities on an MRI examination acquired only a few days after symptom onset led us to speculate that the infection originated in the left L4-L5 zygoapophyseal joint and spread to contiguous tissues, both inside and outside the lumbar canal. The three most common presenting symptoms of spinal epidural abscess are back pain, fever, and neurological deficit; however, these symptoms do not always occur together, contributing to the delayed diagnosis, which is reported in 50%–75% of cases.3Reihsaus E. Waldbaur H. Seeling W. Spinal epidural abscess: a meta-analysis of 915 patients.Neurosurg Rev. 2000; 23: 175-204Crossref PubMed Google Scholar Surgery is reserved for nonantibiotic responders or in cases of neurologic deficit. Lumbar SEA and SAFJ are clinical emergencies with significant morbidity and mortality, particularly when there is a delayed diagnosis. Therefore, early clinical suspicion, diagnosis, and treatment are essential to obtain a favorable outcome.4Davis D.P. Wold R.M. Patel R.J. Tran A.J. Tokhi R.N. Chan T.C. et al.The clinical presentation and impact of diagnostic delays on emergency department patients with spinal epidural abscess.J Emerg Med. 2004; 26: 285-291Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar The authors declares that there is no conflict of interest regarding the publication of this paper. The following is the supplementary data to this article: Download .docx (2.14 MB) Help with docx files Multimedia component 1

Effectiveness of oral cephalexin in antibiotic-course completion for methicillin-susceptible Staphylococcus aureus-induced bacteremic vertebral osteomyelitis

BackgroundMethicillin-susceptibleStaphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO.MethodsThis retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment.ResultsAmong 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5–80.5] years; Charlson Comorbidity Index 2 [0–4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500–2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32–61; 21–86), 29 (19–82; 8–251), and 86 (59–125; 37–337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5–350) days.ConclusionsIn patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.

Safety and feasibility of outpatient parenteral antimicrobial therapy for patients with spinal infection

Outpatient parenteral antimicrobial therapy (OPAT) is a cost-effective method of administering intravenous antimicrobial therapy. Although OPAT is well established in the UK and US healthcare systems, few centres in Europe perform it. Here we analysed OPAT for the treatment of patients with spinal infections at our institution. In this retrospective study, patients with spinal infection who required intravenous (i.v.) antimicrobial treatment between 2018 and 2021 were analysed. The duration of short-term antimicrobial treatment for skin and soft tissue infections and complex infections requiring long-term antimicrobial treatment, such as spinal bone or joint infections, were analysed. All patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed. For this study a total of 52 patients who were treated via OPAT due to spinal infections were analyzed. In 35 cases (69.2%) complex spinal infection was reason for i.v. antimicrobial therapy. Surgery was required in 23 of these 35 patients (65.7%). The average hospital stay for these patients was 12 ± 6 days. The remaining 17 patients were treated for an infection of the soft tissue or the skin and hospital stay for these patients was on average 8 ± 4 days. Gram-positive organisms were isolated in 64.4%. Staphylococcus aureus followed by other Staphylococcus species, was the most common detected organism. After discharging i.v. antimicrobial treatment was given for an average of 20 ± 14 days. The duration of antimicrobial treatment for soft tissue was 10.8 ± 8 days, and for complex infections 25.1 ± 18 days. The mean follow-up was 21 ± 14 months. There was one case of readmission due to treatment failure. There were no difficulties encountered in implementing OPAT. OPAT is a feasible and effective option for delivering intravenous antimicrobial therapy to patients with spinal infections who can be managed without hospitalisation. OPAT offers patient-centred treatment at home while avoiding the risks associated with hospitalisation, with high levels of patient satisfaction.

STIMULAN® IN ORTHOPAEDIC SURGERY: TECHNIQUE AND INDICATIONS FOR USE

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution.Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection.We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well.

A rare case report of ruptured splenic abscess causing pneumoperitoneum in a tertiary care centre

Splenic abscess is a very rare entity but potentially a life threatening disease. In autopsy studies, the incidence of splenic abscess is found to be 0.05 to 0.7%. The most common cause of splenic abscess is through haematogenous spread. It usually occurs due to spread of infection from endocarditis or some contiguous infection sites. High risk individuals include immunocompromised patients, hemoglobinopathies, and diabetes mellitus. Early in diagnosis of these abscesses can be done by the combination of clinical suspicion and computed tomography scan of the abdomen. The management of these abscesses includes medical therapy, CT-guided percutaneous aspiration, and splenectomy. Recent studies have stressed on the change in clinical spectrum, thereby indicating that intravenous antimicrobial therapy alone for patients with splenic abscess has a significant role in its management. However, many studies reveal that splenectomy is necessary for a ruptured splenic abscess with peritonitis.

Observational Study on Clinical Features and Management of Skull Base Osteomyelitis in Hospitalised Patients at a Tertiary Care Hospital.

1. To study the various clinical presentations, microbiological and radiological profiles in patients of skull base osteomyelitis, to know about the underlying comorbidities or immunocompromised status and its relation to the disease and its management. 2. To study the effect of long term intravenous antimicrobial therapy with respect to clinical outcomes and radiological improvement and to study the long term outcomes of the treatment. This is an observational prospective and retrospective study. Thirty adult patients who were diagnosed with skull base osteomyelitis by clinical/microbiological and or radiological features were treated with long term intravenous antibiotics according to pus culture and s for 6-8weeks and they were followed up for 6months. Clinical improvement in symptoms and signs, radiological imaging features and pain score were assessed after 3 and 6months. We noticed in our study that skull base osteomyelitis are more common in older patients with male predominance. Presenting symptoms include ear discharge, otalgia, hearing, cranial nerve palsy. Immunocompromised state, mainly Diabetes mellitus is closely associated with skull base osteomyelitis. Majority of patients showed Pseudomonas related species on pus culture and sensitivity. All the patients showed temporal bone involvement in CT and MRI. Other bones involved were shenoid, clivus and occipital bone. Majority showed good clinical response to intravenous ceftazidime, combination of piperacillin and tazobactum, followed by combination of piptaz and Ciprofloxacin. Treatment duration was 6-8weeks. All patients showed clinical improvement in symptoms and relief in pain after 3 and 6months. Skull base osteomyelitis is a rare condition, most commonly seen in elderly patients with diabetes mellitus and or other immunocompromised condition. Pseudomonas related species are the major causes of skull base osteomyelitis. Long term pus culture and sensitivity bases intravenous antibiotic therapy is the main stay of treatment.

Physician Financial Incentives for Use of Outpatient Intravenous Antimicrobial Therapy: An Interrupted Time Series Analysis.

In 2011, policymakers in British Columbia introduced a fee-for-service payment to incentivize infectious diseases physicians to supervise outpatient parenteral antimicrobial therapy (OPAT). Whether this policy increased use of OPAT remains uncertain. We conducted a retrospective cohort study using population-based administrative data over a 14-year period (2004-2018). We focused on infections that required intravenous antimicrobials for ≥10 days (eg, osteomyelitis, joint infection, endocarditis) and used the monthly proportion of index hospitalizations with a length of stay shorter than the guideline-recommended "usual duration of intravenous antimicrobials" (LOS < UDIVA) as a surrogate for population-level OPAT use. We used interrupted time series analysis to determine whether policy introduction increased the proportion of hospitalizations with LOS < UDIVA. We identified 18 513 eligible hospitalizations. In the pre-policy period, 82.3% of hospitalizations exhibited LOS < UDIVA. Introduction of the incentive was not associated with a change in the proportion of hospitalizations with LOS < UDIVA, suggesting that the policy intervention did not increase OPAT use (step change, -0.06%; 95% confidence interval [CI], -2.69% to 2.58%; P = .97 and slope change, -0.001% per month; 95% CI, -.056% to .055%; P = .98). The introduction of a financial incentive for physicians did not appear to increase OPAT use. Policymakers should consider modifying the incentive design or addressing organizational barriers to expanded OPAT use.

An evaluation of risk factors for readmission in patients receiving outpatient parenteral antimicrobial therapy.

Outpatient parenteral antimicrobial therapy (OPAT), when required, is beneficial to patients and healthcare systems by reducing hospital length-of-stay, providing cost savings, and improving patient satisfaction. The purpose of this study is to determine readmission rates and associated risk factors in patients receiving OPAT at home. This retrospective study included hospitalized patients 15 years and older who were discharged on intravenous antimicrobial therapy via OPAT at home between January 2018 and December 2019. Patients receiving antimicrobials at a skilled nursing facility, long-term acute care, or dialysis center, and those who began OPAT at home directly from the outpatient setting were excluded. The primary outcome of this study was all-cause 30-day readmission rate. Secondary outcomes included 90-day readmission rate, rates of complications related to OPAT, emergency department visits during OPAT, and predictors of all-cause 30-day readmission through a logistic regression analysis. Two hundred individual patients were included in the analysis; 60% were male and the mean age was 49 years. The most common indications for OPAT at home were bone and joint infection (52%) and bacteremia (26%). Forty patients (20%) experienced an unplanned, all-cause 30-day readmission, with a total of 48 readmission events. Of the 40 patients who were readmitted within 30 days, 20 (50%) were due to non-OPAT related reasons. Sixty patients (30%) experienced an OPAT-related complication, and chronic kidney disease was found to be an independent predictor of readmission (OR: 2.8, 95% CI: 1.0-7.6). Patients receiving OPAT at home are at increased risk for early hospital readmission, but it is often due to reasons not associated with OPAT. Patients with chronic kidney disease beginning OPAT at home should be closely monitored after discharge.

Opportunities, associations, and impact of early intravenous to oral antimicrobial switch for hospitalized patients in Ethiopia.

Short intravenous antimicrobial therapy for 2-3 days followed by its per oral comparable antimicrobial course is a crucial part of the antimicrobial stewardship program. However, nothing is known about this practice in Ethiopian hospitals. Therefore, this study assessed the proportion, associations, and outcomes of early intravenous to per oral antimicrobial switch for patients who were admitted to the three wards of Ambo University Referral Hospital. A hospital-based prospective cohort pilot study was conducted. During the 3-month period, 117 patients met initial inclusion criteria and were followed until Day 3 of intravenous antimicrobial. Of these, 92 (78.6%) subsequently met criteria for early intravenous to per oral switch and are the cohort investigated in this study. Written informed consent was sought from participants and/or parents or guardian for ages 15-17 years. Logistic regression models and independent t-tests were done with a significance of p ⩽ 0.05. Out of 92 study participants, early intravenous to per oral antimicrobial switch was done only for 36 (39.1%). The only independent predictors for lack of early intravenous to per oral antimicrobials switch were poly-pharmacy (adjusted odds ratio = 3.4 at 95% confidence interval, 1.036-11.16; p = 0.044). There was a significant difference in terms of mean length of hospital stay (8.80 ± 3.57 versus 3.17 ± 0.74; p < 0.0001), in-hospital complication rate (95% versus 5%; p < 0.0001), and the mean cost of healthcare in Ethiopian Birrs (652.29 ± 403.29 versus 126.67 ± 29.47; p < 0.0001) between the comparator/early intravenous to per oral not switched and early switched group, respectively. The proportion of early intravenous to per oral antimicrobial switch was unsatisfactory. There was a significant difference between the intervention and comparator groups in terms of length of hospital stay, in-hospital complications, and extra cost. Therefore, implementation of interventions that improve the practice of early intravenous to per oral switch is needed urgently.

長期間の抗菌薬経静脈投与を要した頭蓋底骨髄炎例

Skull-base osteomyelitis occurs as a result of spread of inflammatory disease around the temporal bone into the adjacent skull base, and carries a poor prognosis. Occasionally, patients present with paralysis of the lower cranial nerves, which further worsens the survival. Prolonged intravenous antibiotic therapy for six to eight weeks is needed for treatment. Herein, we present a case of skull-base osteomyelitis caused by Pseudomonas aeruginosa that developed in a 78-year-old male patient with diabetic nephropathy who was under maintenance hemodialysis. He presented to our hospital with the complaints of earache and otorrhea on the left side. Exploratory tympanotomy revealed pus and granulation tissue filling the tympanic cavity and mastoid, and destruction of the tympanic portion of the temporal bone; based on the findings and results of pus culture, we made the diagnosis of skull-base osteomyelitis caused by Pseudomonas aeruginosa. While the osteomyelitis was gradually improving with intravenous meropenem, the patient desired early discharge from the hospital. Therefore, the intravenous antibiotic therapy was switched earlier than intended to oral antimicrobial therapy, which led to progression of the disease, and the patient presented with lower cranial nerve palsies three months after his discharge. He was initiated again on intravenous meropenem. While the osteomyelitis improved gradually with the intravenous antimicrobial therapy for two months, the levels of inflammatory markers, such as the serum c-reactive protein, increased again soon after discontinuation of the intravenous antibiotic therapy. Therefore, we decided to continue the patient on intravenous meropenem every other day administered at the outpatient clinic after dialysis. The treatment was continued for four months after discharge, and the improvement was maintained. We reaffirmed the importance of long-term intravenous antibiotic therapy to treat skull-base osteomyelitis. Intravenous antibiotic administration every other day at the outpatient clinic after dialysis could be a useful treatment strategy to treat skull-base osteomyelitis in patients under maintenance hemodialysis.