Long-term Antimicrobial Therapy Research Articles

A Review of the Clinical Utilization of Oral Antibacterial Therapy in the Treatment of Bone Infections in Adults.

Chronic osteomyelitis in adults is managed with prolonged courses of intravenous antibiotics in conjunction with surgical debridement of necrotic bone. Over the past 40 years, there has been no paradigm shift in this approach, as randomized controlled trials of this standard of care compared to alternatives such as prolonged oral antibiotics are scarce. However, there have been many small trials, case reports, and review papers evaluating the effectiveness of oral treatment for chronic osteomyelitis. The oral route for infections requiring prolonged treatment is intuitively and practically more favorable due to several advantages, the most important of which is the avoidance of long-term IV antimicrobial therapy with its complications, inconvenience, and cost. In this paper, we review the literature evaluating oral antibiotic therapy in the management of chronic bone infections since 1975. The majority of osteomyelitis infections are caused by Staphylococcus aureus, hence we focus on its treatment using oral antibiotics; however, we also emphasize subpopulations of patients with diabetes, implanted hardware, and with less common bacterial organisms. The primary objective of this review is to promulgate clinical recommendations on the use of oral antibiotics in bone infections in the context of initial therapy, transition from intravenous therapy, and the role of chronic suppression. The secondary objective is to summarize current knowledge of the specific oral antimicrobial agents that are commonly utilized, together with a synopsis of the available literature pertaining to their pharmacokinetic/pharmacodynamic properties and duration of therapy in bone infection.

Ag+-Adsorbing Semiconducting Polymer Nanosponge for Smart Local Treatment of Wound Infection.

Nanoplatform combined with photothermal therapy (PTT) and silver nanoparticles have been widely used to combat bacterial infections. However, the development of environmentally benign antibacterial nanoplatforms with controllable and long-term antibacterial activity is still challenging. Herein, we synthesized an Ag+-adsorbing organic semiconducting polymeric nanosponge (PDPP3T NPe@Ag+) to realize Ag+ enhanced photothermal anti-infective therapy. Furthermore, the PDPP3T NPe@Ag+ sponge can also spatiotemporally release silver ions in a pH/NIR light-responsive manner for controllable and long-term antimicrobial therapy. Owing to good biocompatibility and controlled release of silver ions, PDPP3T NPe@Ag+ can effectively kill bacteria in vitro and promote wound healing in vivo. We expect that this antimicrobial platform could be utilized as a robust antibacterial agent for infective therapy.

P252 Proposed plan for oxygen therapy as an adjuvant to antibiotics in cystic fibrosis

There is a clear need for new antibiotics to improve the efficacy of long-term antimicrobial therapy in pwCF. Cefiderocol is currently licensed for the treatment of infections due to Gram-negative organisms with limited treatment options. The aim of this study was to determine the susceptibility of a broad range of CF Gram-negative pathogens to cefiderocol and relevant comparator antibiotics.

Antimicrobial Therapy Duration for Bloodstream Infections Caused by Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex: A Retrospective Cohort Study.

Ideal therapy duration for Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex (ABC) bloodstream infections (BSI) is not defined, especially in the context of carbapenem resistance. In this study, we compared short- (≤7 days) and long-term (>7 days) antimicrobial therapy duration for these infections. We performed a retrospective cohort study in two tertiary-care hospitals in Porto Alegre, Brazil, from 2013 to 2019. Eligible patients aged ≥18 years were included and excluded for the following criteria: polymicrobial infections, treatment with non-susceptible antibiotics, complicated infections, or early mortality (<8 days of active antimicrobial therapy). The 30-day mortality risk was evaluated using a Cox regression model. We included 237 BSI episodes, 51.5% caused by ABC and 48.5% by Pseudomonas aeruginosa. Short-term therapy was not associated with 30-day mortality, adjusted hazard ratio 1.01, 95% confidence interval 0.47-2.20, p = 0.98, when adjusted for Pitt score (p = 0.02), Charlson Comorbidity Index score (p < 0.01), and carbapenem resistance (p < 0.01). Among patients who survived, short-term therapy was associated with shorter hospital stay (p < 0.01). Results were maintained in the subgroups of BSI caused by carbapenem-resistant bacteria (p = 0.76), ABC (p = 0.61), and Pseudomonas aeruginosa (p = 0.39). Long-term therapies for non-complicated Pseudomonas aeruginosa and ABC BSI were not superior to short-term therapy for 30-day mortality.

Ocular Mycobacterium haemophilum infection originating in the cornea: a case report

BackgroundMycobacterium haemophilum is a slow-growing non-chromogenic nontuberculous Mycobacterium species that can cause skin infection or arthritis in an immunocompromised population or in children. Primary infection of the healthy adult cornea is rare. The special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical manifestation and treatment process of corneal infection and notify the awareness of M. Haemophilus keratitis among clinicians. This is the first case report of primary M. haemophilum infection in the cornea of healthy adults reported in the literature.Case presentationA 53-year-old healthy goldminer presented with left eye redness and a history of vision loss for four months. The patient was misdiagnosed with herpes simplex keratitis until M. haemophilum was detected using high-throughput sequencing. Penetrating keratoplasty was performed, and a large number of mycobacteria were detected by Ziehl-Neelsen staining of the infected tissue. Three months later, the patient developed conjunctival and eyelid skin infections that manifested as caseous necrosis of the conjunctiva and skin nodules. After excision and debridement of the conjunctival lesions and systemic antituberculosis drug treatment for 10 months, the patient was cured.ConclusionM. haemophilum could cause primary corneal infection in healthy adults, which is an infrequent or rare infection. Owing to the need for special bacterial culture conditions, conventional culture methods do not provide positive results. High-throughput sequencing can rapidly identify the presence of bacteria, which aids in early diagnosis and timely treatment. Prompt surgical intervention is an effective treatment option for severe keratitis. Long-term systemic antimicrobial therapy is crucial.

Outcomes and risk factors for failure after débridement, antibiotics, and implant retention for elbow periprosthetic joint infection

Evidence for the management of periprosthetic joint infection (PJI) after total elbow arthroplasty is sparse, particularly in regard to débridement, antibiotics, and implant retention (DAIR). This study explored the outcomes of DAIR and analyzed risk factors for failure. A retrospective cohort study of patients 18years or older diagnosed with elbow PJI and managed with DAIR between January 1, 2003, and December 31, 2018, at a single institution was performed. Twenty-six elbows met the inclusion criteria during the study period. All DAIR procedures included in this study represented an attempt to manage an acute PJI with surgical irrigation and débridement without removal of the elbow arthroplasty components, followed by long-term systemic antimicrobial therapy. DAIR failure was defined as recurrence of PJI, unplanned re-operation for infection, or death secondary to infection. A Cox proportional hazards model was used to identify possible risk factors for failure. DAIR failed in 17 cases of elbow PJI with a failure rate of 65% at 2years (95% confidence interval: 41.3%-79.6%). The median time to failure from DAIR was 43days (interquartile range: 27-114). We found that DAIR failed in all cases with sinus tracts or negative cultures. The group with favorable outcomes had a shorter median duration of symptoms (5 vs. 18days, P=.65) and a higher proportion of monomicrobial infections (58.8% vs. 88.9%, P=.19) compared to those with unfavorable outcomes. However, with the numbers available, none of the possible risk factors analyzed for association with failure reached statistical significance. DAIR for elbow PJI was associated with high rates of failure. Possible risk factors for failure may include the presence of sinus tract, longer duration of symptoms, and culture-negative infection. Although the relatively low morbidity of DAIR compared with total elbow arthroplasty implant resection for a one-stage or two-stage reimplantation is attractive, patients considered for DAIR must know that the chance of success is limited to approximately 35%.

What is the role of the clinical microbiology laboratory in the care of diagnostically challenging OPAT patients? Illustrative cases and literature review.

Optimal care of patients requiring long-term outpatient parenteral or oral antimicrobial therapy by infectious diseases (ID) specialists is facilitated by an accurate microbiologic diagnosis. Close collaboration between ID specialists and the clinical microbiology laboratory for routine or specialized molecular testing can result in more accurate diagnoses, streamlined antimicrobial regimens, and improved patient outcomes.

Анализ эффективности применения витаминно-минерального комплекса на течение беременности

Pregnancy increases the need for vitamins, which is almost impossible to compensate for by changing dietary intake. This need is increased by negative environmental impacts, several diseases of the gastrointestinal tract and liver, long-term illnesses, antimicrobial therapy, and other factors. Objective. To study the effect of vitamin and mineral complex (VMC) “Miteravel Plus” on overall well-being and sleep quality, skin, hair, and nail conditions, as well as gastrointestinal tract function in pregnant women and in women in the preconception period. Patients and methods. This prospective observational study included 1544 patients: 246 women preparing for pregnancy and 1298 pregnant women. All patients took “Miteravel Plus” one capsule once a day. The duration of VMC administration was left to the discretion of pregnant women and their attending physicians. Two questionnaires were carried out during the study: before and 1 month after the use of VMC. Results. Administration of VMC helped to decrease nausea and vomiting in the first trimester of pregnancy, increase physical activity, improve sleep quality and conditions of skin, hair, and nails (p &lt; 0.05). Conclusion. Vitamin and mineral complex “Miteravel Plus” compensates for a greater demand for vitamins and micronutrients in the preconception period and during pregnancy, improving the overall well-being of women in early gestation. Key words: pregnancy, dyssomnia, nausea and vomiting of pregnancy, gastrointestinal function

Polycaprolactone-Coated Alginate/b-Tricalcium Phosphate Beads to Locally Deliver Vancomycin: A Pilot Study

Orthopedic device-related infections (ODRI) are difficult to control and the management of ODRI most frequently includes surgery and long-term antimicrobial therapy. Local application of vancomycin through a biodegradable carrier like alginate would provide a valuable tool, although it is hard to control the drug-release for a prolonged period of time due to its permeability. Coating with hydrophobic polymer such as polycaprolactone (PCL) may sustain the vancomycin release. We fabricated four types of vancomycin containing alginate/b-TCP beads (uncoated, coated with 1.25 w/v%, 2.5 w/v%, and 5.0 w/v% PCL). Scanning electron microscope (SEM) revealed that b-TCP particles were uniformly distributed on the surface of the uncoated beads and the most homogenous coating layer was observed using 2.5 w/v% PCL. Vancomycin release and its bioactivity were measured at the designated time points (1, 4, 12, 24 hours, then every day until disintegration). Burst release occured on the first hour, day 1, 2 and 6 respectively. The beads without coating dissolved at day 3, and those with different coatings dissolved at day 5, 6, and 9. The minimum concentration of the vancomycin in the elution was approximately 5 mg/L, higher than the vancomycin’s minimum inhibitory concentrations (MICs) for Methicillin-resistant Staphylococcus aureus (MRSA). PCL-coated alginate/b-TCP beads loaded with vancomycin may provide a potential local drug delivery device for the adjuvant antimicrobial therapy of the ODRI.

Successful management of a mediastinum abscess with sternum destruction caused by MSSA bloodstream infection

BackgroundMultiple deep organ abscesses associated with Staphylococcus aureus bloodstream infection (SAB) have a high mortality rate, requiring rapid removal or drainage of infective foci with long-term appropriate antimicrobial therapy. Cases in which infective foci cannot be completely removed are challenging for their management.Case presentationA 77-year-old man developed multiple deep organ abscesses associated with SAB. The left anterior chest subcutaneous abscess continued into the right anterior mediastinum and had extensively destroyed the sternum. Necrotizing fasciitis was observed in the bilateral feet. The anterior mediastinum abscess was drained percutaneously, and the chest wall abscess was incised cautiously without causing an external pneumothorax. On the next day, right-sided pyothorax had developed, requiring pleural drainage. On the third day, debridement of anterior chest wall abscess followed by concurrent thoracoscopic pleural curettage and debridement of bilateral feet were performed. Thorough sternal debridement was not performed, considering the risk of respiratory failure due to the sternal defects. On the 24th day, sternum debridement and incisional drainage of sciatic rectus fossa abscess, which had been present since the time of admission, were performed to control persistent infection. The caudal half of the sternal body was resected, leaving the costal cartilage attachments. The general condition further improved without postoperative respiratory failure after the second surgery, leading to a transfer to the general ward on the 43rd day.ConclusionsWe successfully treated the severe multiple deep organ abscesses, including a mediastinum abscess with sternum destruction, by repeated removal of the infective foci while avoiding respiratory failure due to excessive debridement of the anterior chest wall, including the sternum.

Severe mandibular osteomyelitis and exfoliation of a mandibular canine tooth in a Vietnamese potbellied pig

A 10-year-old male castrated Vietnamese potbellied pig presented for evaluation of a dermal mass present on the left cervico-mandibular region. The patient had a mass removed 6 years earlier from the same region, which was diagnosed as squamous cell carcinoma on histopathology. On physical examination, all vital parameters, including heart rate, respiratory rate and temperature, were within normal reference ranges, and the owner reported a normal appetite with no recent history of weight loss. Upon intubation for the dermal mass removal, a large heterogeneous mass of material was observed in the rostral aspect of the left mandible (Figure 1). Once removed, the mass appeared to be grossly composed of foodstuffs, hair, and a firm, mineralized segment of unknown material (Figure 2a). Within the contents of this debris, the left mandibular canine tooth (304) or tusk was identified. For the size of the mass of material, there was minimal inflammation associated with the gingiva and the mucosa (Figure 2b). There did not appear to be any evidence of displacement of the remaining teeth in the area. The periodontal attachment appeared to be normal in the remaining teeth. Computed tomography (CT) of the head was performed with the patient anaesthetized as previously described1 and positioned in sternal recumbency. Findings included severe, multifocal, chronic periodontal disease. The left mandibular canine tooth (304) or tusk was absent, and there was a large bony defect associated with the left mandibular body along the alveolar margin. The bony defect continued to affect the buccal aspect of the mandibular body (Figure 3). There was also extensive periapical lysis and evidence of external tooth resorption of the right mandibular canine tooth (404). The radiographic dental abnormalities were consistent with severe diffuse mandibular osteomyelitis characterized by multifocal moth-eaten bone lysis and irregular periosteal new bone formation, and multiple draining tracts from the right ventral mandible. Additional radiographic findings included absence of all premolar and molar teeth except the right first maxillary premolar (105), multifocal periapical lysis of the remaining teeth, bilateral medial retropharyngeal lymphadenopathy, and evidence of bilateral otitis externa and right otitis media. Miniature companion pigs (MCPs) are increasing in popularity as companion animal pets in North America.2 While data for exact numbers are limited, MCPs first appeared in the United States in the 1980s, with a dramatic increase in popularity over the past 17 years.3 With the increase in numbers, preventive care strategies are essential to improve animal health and welfare. Commonly reported dental pathologies in MCPs include missing teeth (most commonly the first mandibular premolar), periodontal disease, and tooth resorption.4 Early diagnosis of dental disease and mandibular osteomyelitis is important for companion animal pigs, considering their potentially long life span. Extraction of an infected tusk can be quite challenging. In cases of severe infection and disease, the integrity of the mandible can be affected to the point where it can be unstable after the extraction.5 Osteomyelitis can be managed with long-term antimicrobial therapy, including oral, injectable, and regional infusion of antibiotic-impregnated compounds, depending on lesion location.6 Removal of the infected nidus, in many cases the tooth, is critical for a positive long-term outcome. A complete oral assessment with inclusion of dental radiographs in MCPs should be considered for proper preventative dental care.4 As evidenced by our case, CT is also beneficial for a thorough oral evaluation and dental assessment. The authors declare no conflict of interest. This case represents a retrospective clinical case report and not a prospective study that requires institutional approval. The authors received no specific funding for this work. Open access funding provided by the Iowa State University Library.

Efficacy and Safety of Dalbavancin Monotherapy as Salvage Treatment for Bone and Joint Infection

Bone and joint infection (BJI) treatment is challenging with significant morbidity and mortality. Dalbavancin is a semi-synthetic lipoglycopeptide analogue of the teicoplanin class that exhibits bactericidal activity and a long half-life. The use of dalbavancin may be an option in cases of gram-positive BJI. From November 2017 to April 2019, dalbavancin was used in monotherapy as a salvage option for BJI, as follows: 1500 mg, 1st (D1) and 8th (D8) days, repeated if needed. The follow-up period was of 6 months for osteomyelitis and 1 year for prosthetic joint infections (PJIs). The demographics of the 16 patients showed that 75% were men (n=12), with a mean age of 77.8 years [64-90]. The BJI characteristics: 5 cases of vertebral osteomyelitis; 12 cases of lower limb BJI {8 joint infections, among which were 6 PJIs (4 knees, 2 hips) and 4 cases of foot osteomyelitis)}; 2 cases of shoulder PJI. The debridement, antibiotics, irrigation, and implant retention (DAIR) procedure was performed in 83.4% (5/6) of cases. Monobacterial biopsy was obtained in 75% (n=12) of patients with majority of staphylococcus (15/25) dalbavancin susceptible micro-organismes): 14 Staphylococcus aureus (10/14 methicillin susceptible). Twelve patients received 2 doses of dalbavancin. The mean duration of the 1st antibiotherapy was 18.3 days [0-49]. The clinical success rate was 75% at the end of follow-up with no major side effects of dalbavancin. This report highlights the potential role and efficiency of dalbavancin in treating fragile patients who require long-term antimicrobial therapy with excellent tolerance profiles.

Mixed Vaginitis Due to Bacterial Vaginosis and Candidiasis.

The aim of the study was to review recent clinic cases with mixed vaginitis due to bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) with reference to demographics, clinical presentation, diagnosis, and treatment. This is a retrospective chart review of patients defined with mixed vaginitis due to BV and VVC in academic vaginitis clinic over 3 years (2018-2021). Thirty-eight women, mean age 32.6 years, met mixed vaginitis definition criteria. Diagnosis was invariably suspected clinically and rapidly confirmed using standard point of care diagnostic tests. Most patients (>90%) had a history of long-standing recurrent vaginitis both BV and VVC. Condom use was infrequent at 30% and 100% of yeast isolates were Candida albicans. Dual antimicrobial therapy achieved short term therapeutic success in 66.7% with failure in part due to fluconazole resistant C. albicans strains. Mixed vaginitis is not uncommon and serves as a significant therapeutic challenge requiring initial dual antimicrobial therapy and additional consideration for long-term antimicrobial therapy.

Brucella aortitis managed with debridement, extra-anatomical bypass, and long-term antimicrobial therapy.

This report aims to review the management and outcomes of Brucella-associated mycotic aortic aneurysms. This is a retrospective chart review at a tertiary-level healthcare system. IRB approval was waived per policy. We describe a case of Brucella aortitis acquired from habitual contact with wild hogs. Clinical presentation included lower back pain and elevated white blood cell count. Diagnosis was confirmed with imaging showing an infrarenal abdominal aortic aneurysm and serology revealing elevated Brucella antibodies titers. The patient was initially managed with endovascular aortic repair and combined oral and intravenous antibiotics therapy. He then underwent explanation and extra-anatomical bypass due to symptomatic periaortic infection and interval development of type I endoleak. The patient was asymptomatic after his final operation at 24months of follow-up and remained on suppressive oral antibiotic therapy. An aortic aneurysm secondary to Brucella is a rare entity. A detailed history of long-term exposure to animals may be a clue to obtain serologic testing. Operative debridement and re-establishing of reliable blood flow combined with long-term antibiotic suppression are the mainstay of treatment.

Increased diversity, fungal burden, and virulence of oral Candida spp. in patients undergoing anti-tuberculosis treatment

Some studies have demonstrated a high prevalence of Candida species in patients with tuberculosis (TB). This is most likely due to long-term antimicrobial therapy. To date, no longitudinal studies addressed the effects of anti-TB treatment on the fungal burden and virulence of Candida spp. This study investigated the prevalence and virulence of Candida spp. in the oral cavity of 30 TB patients at different stages of treatment through a cohort study. These results were compared with those of 60 systemically healthy individuals in a cross-sectional study.Oral rinse samples from TB patients were collected before 45 and after 120 days of treatment. In the control group, the biological samples were collected only once. Candida spp. were identified by restriction fragment length polymorphism (RFLP) assays, and the following virulence factors were studied: phospholipase C and proteinase production, as well as Candida spp. biofilm and hyphae formation.The clinical diagnosis of TB and its treatment time were associated with the greater fungal burden (p < 0.0001), presence of non-albicans Candida (NAC) species (p = 0.0003), and increased virulence factors when compared with the Candida spp. isolated from systemically healthy individuals. The results showed that anti-TB treatment time was responsible for the increased fungal burden and isolation of NAC in TB patients (p = 0.0233).The increased prevalence, quantification, and virulence of Candida spp. isolated from the oral cavity of TB patients highlight the greater risk of oral lesions and cases of systemic dissemination in these patients.

Treatment of Nocardial Brain Abscess in a Patient With Systemic Lupus Erythematosus and Idiopathic Thrombocytopenic Purpura: Case Report and a Review of the Literature

Brain abscesses due to Nocardia species account for 1-2% of all cerebral abscesses, often in immunosuppressed individuals, with a mortality three times higher than other cerebral abscesses. Early diagnosis and management are vital for good outcomes.We report a case of a right frontal Nocardia brain abscess in an immunosuppressed 38-year-old female. She presented with headaches, confusion, memory deficits, and personality change. She remained systemically well, with normal inflammatory markers. She underwent two open surgical drainages, with excision of the abscess wall. She made an excellent recovery with minimal edema and no contrast enhancement on imaging at eight weeks postoperatively.Management of Nocardia brain abscess includes a prompt diagnosis with direct microscopic examination and initiation of correct antibiotic therapy for good outcomes. We recommend open surgical resection, including excision of the abscess wall, followed by long-term antimicrobial therapy, to enhance the rate of recovery.

Imaging of Cardiac Device-Related Infection

Cardiac devices are frequently used in different cardiovascular conditions for the purpose of morbidity or mortality prevention. These include cardiac implantable electronic devices (CIED) like permanent pacemakers and implantable cardiac defibrillators, ventricular assistance devices (VADs), left atrial appendage occlusion (LAAO) devices like the Watchman™, atrial and ventricular septal occluders like the Amplatzer™, among others. In the past years, there has been an increase in the development of these devices as a result of a rise in the number of indications for implantation, paired with the aging and more medically complex patient population. This has led to an increase in the incidence of cardiac device-related infections, one of the most feared and serious complications which is associated with significant morbidity, mortality and financial burden. Accurate diagnosis of cardiac device-related infections is essential given the management implications which often involve removal of the infected device, removal of other prosthetic material and long-term antimicrobial therapy. Clinical and laboratory data are useful diagnostic tools but multimodality imaging is often necessary. The recently published 2020 European Heart Rhythm Association International Consensus document, which is endorsed by many expert societies, has recommended the use of multimodality imaging for the diagnosis of CIED infections. (1) This allows better disease characterization by identifying abnormal fluid collections and guiding aspiration for both diagnostic and therapeutic purposes (i.e. soft tissue ultrasound and computed tomography), evaluation for local extent of disease (i.e. transesophageal echocardiogram to evaluate for concomitant infective endocarditis), embolic manifestation of disease (i.e. computed tomography and magnetic resonance imaging) and metabolic tissue characterization (positron emission tomography and tagged white blood cell scan). (2) In addition, computed tomography (CT) allows for pre-procedural planning which has shown to be associated with better procedural outcomes.

Metal-Organic Framework Enhanced Cellular and Humoral Immune Response Against Sepsis Causing Infection

Urinary tract infection (UTI) is the most common adult bacterial infections worldwide, with ~80% of all uncomplicated UTI caused by uropathogenic E. coli (UPEC). While anyone can develop a UTI, women in their 20’s and postmenopausal women are at particularly high risk—indeed, half of all women will develop a UTI in their lifetime. Even with antibiotic therapy, 25-50% of patients will experience recurrence within a year.1 Initial and subsequent UTIs can alter bladder epithelial cell barrier function, which in turn creates an environment more favorable to subsequent infection.2 This results in recurrent UTI, which requires long-term antimicrobial therapy and can reoccur in a patient indefinitely, causing a lifetime of pain, discomfort, and an elevated risk of septicemic death.3 Unfortunately, antibiotic resistance makes treating UTIs less effective. Indeed, 10–25% of uncomplicated UTI patient isolates are resistant to trimethoprim/sulfamethoxazole (TMP/SMX)—the standard-of-care antibiotic regime for UTI.4 , 5 Alarmingly, >70% of postmenopausal recurrent UTI patients are either allergic or resistant to TMP-SMX.5 Given the ubiquity of these infections and the high likelihood of recurrence, the societal cost is estimated to be over $5 billion each year in the US alone.6 A prophylactic or therapeutic vaccine would be an ideal first line of defense against UTIs for high risk groups, but no FDA-approved vaccines against UTI—or indeed any pathogenic E. coli infection—exist.7

Prospective Pilot Study of Cyclophosphamide as an Adjunct Treatment in Patients With Adult-Onset Immunodeficiency Associated With Anti-interferon-γ Autoantibodies.

BackgroundAdult-onset immunodeficiency associated with interferon-γ autoantibody (IGA) is an emerging disease. The majority of patients require both antimicrobial and immunosuppressive treatments. However, anti-CD20 therapy is not fully accessible in a resource-limited setting to date.BackgroundThe objectives of this work were to study the efficacy of cyclophosphamide treatment and the role of laboratory biomarkers for disease progression monitoring.MethodsA prospective pilot cohort study was conducted among patients with anti-interferon-γ autoantibodies (IGA) who had recurrent infections and required long-term antimicrobial therapy between 2015 and 2018. The patients were categorized into 2 groups: receipt of intravenous cyclophosphamide (IVCY) and receipt of anti-CD20 therapy (RTX). Clinical and laboratory data were determined.ResultsA total of 17 IGA patients were enrolled. Prolonged fever was the most common manifestation, and the most common infection identified was nontuberculous mycobacterial infections. Both were found in 88.24% of all patients.After completion of IVCY, 9/11 patients achieved complete remission and tended to reach remission faster compared with individuals in the RTX group. The median duration from treatment initiation to remission (interquartile range) was 84 (42–154) days in the IVCY group and 99 (51–202) days in the RTX group. In remission patients, the biomarkers of interest had normalized after treatment, except interferon γ autoantibody titers. There were no differences in adverse events among the 2 groups.ConclusionIVCY may be considered as alternative therapy in this population, especially in resource-limited countries. A comparable clinical outcome to RTX may support its use on a larger scale. However, further study is encouraged.

The direct anterior approach: treating periprosthetic joint infection of the hip using two-stage revision arthroplasty.

Either one- or two-stage revision arthroplasties can be used for the treatment of chronic periprosthetic joint infection (PJI) after total hip arthroplasty (THA). We report our results following two-stage revision surgery performed through the direct anterior approach (DAA) interval using a custom-made articulating spacer. Between 2009 and 2014, 49 patients (49 consecutive procedures) had surgery through either a DAA or extended DAA approach. Each patient received perioperative intravenous administration of antibiotics. A custom-made spacer was implanted after explanting cup and stem and following extensive debridement. Broad-spectrum antibiotics were administered during the immediate perioperative period and then adjusted according to the infecting organism. Complication rates and eradication rates were observed. WOMAC patient assessments were administered preoperatively and one-year postoperatively. Of the 49 study patients, five had a recurrence of the infection after the second-stage revision, five had a proximal periprosthetic fracture during the first stage procedure and one patient had a transient femoral nerve palsy that resolved fully within the first postoperative year. 30 different microorganisms were identified on intraoperative specimens. The average time between first and second stage procedure was 65.7days (range 21-132days). Eradication of infection was defined as healed wound without fistula, no drainage, no recurrence of the infection, no subsequent surgical intervention for persistent or perioperative infection after second stage revision and no long-term (> 6months) antimicrobial suppression therapy. Eradication rate of infection in our study was 89.8%. Postoperative WOMAC scores improved significantly CONCLUSION: The preliminary clinical results for the custom-made spacer technique implanted through the DAA are promising. Therefore, we believe the DAA can be used safely as a standard operative approach for two-stage revision procedures.