Oral Suppressive Therapy Research Articles

Trichosporon inkin and Cutibacterium acnes bioprosthetic aortic valve endocarditis and prosthetic aortic root abscess with multi-focal emboli

This report presents the first case of a patient with dual pathogen-associated bioprosthetic aortic valve endocarditis, prosthetic aortic root abscess and multifocal septic emboli, caused by both Trichosporon inkin and Cutibacterium acnes. A 67-year-old male with a prosthetic aortic root replacement, bioprosthetic aortic valve and pacemaker presented with pyrexia, right arm numbness and confusion. Multiple left-sided embolic infarcts were found on brain imaging, eye examination was consistent with right-sided fungal endophthalmitis, and an aortic valve vegetation and aortic root abscess were visualised on trans-oesophageal echo. Pre-operative blood cultures were negative. Revision surgery tissue samples grew Trichosporon inkin and Cutibacterium acnes. Post-operatively, he was treated with 42 days of meropenem and 150 days of antifungals (ambisome plus flucytosine plus intravitreal voriconazole, followed by oral voriconazole), after which he was switched to long term oral suppressive therapy with doxycycline and fluconazole. Twelve months post operatively, he is well and there is no evidence of recurrence. Trichosporon prosthetic valve endocarditis has a 62% one-year mortality rate. This case presented additional complexity: dual infection with Cutibacterium acnes, multi-focal embolic disease, difficulty in obtaining a pre-operative microbiological diagnosis, and difficulty with antifungal treatment (toxicity risk, drug interactions, minimal evidence-based for treatment). Managing complex cardiothoracic infections involving prosthetic material, such as that described, requires a multi-disciplinary approach, involving cardiothoracic surgeons, infection specialists and pharmacists, and other allied health professionals if necessary, to optimise patient care and reduce morbidity and mortality.

Peri-Prosthetic Joint Infection in Patients Prescribed Suppressive Antibiotic Therapy Undergoing Primary Total Joint Arthroplasty: A 1:4 Case Control Matched Study.

Background: Oral suppressive antibiotic therapy (SAT) has emerged as a potential means to increase rates of infection-free survival in many complex peri-prosthetic joint infection (PJI) cases after total joint arthroplasty (TJA). The purpose of the present study is to evaluate the risk of PJI of a new primary TJA in patients on oral SAT. Patients and Methods: A retrospective matched cohort study from five hospitals in a 20-year period within a large hospital network was performed. Inclusion criteria consisted of patients over age 18 undergoing primary TJA, with any order for oral long-term (>6 months duration) SAT, and minimum of one-year clinical follow-up. Patients were matched 1:4 on age, gender, body mass index (BMI), hip or knee surgery, diabetes mellitus, smoking status, and indication for primary TJA. Student t-test, Fisher exact, and χ2 tests were utilized for group comparisons. Our study was powered to detect a 10.5% increase in PJI incidence compared with a 1% baseline rate of PJI. Results: We identified 45 TJA in 33 patients receiving SAT, which were matched to 180 control cases. There was no difference in the rate of development of PJI at any time point within follow-up between the SAT cohort and control group (2.22% vs. 1.11%; p = 0.561). Conclusions: We found a 2.22% rate of PJI in a cohort of patients receiving SAT identified over a 20-year period. As the clinical scenario of primary TJA while on SAT is rare but likely to become more prevalent, future large-scale studies can be performed to better clarify rates and risk of PJI in this population.

LONG-TERM ORAL SUPPRESSIVE ANTIBIOTIC THERAPY FOR PROSTHETIC VALVE ENDOCARDITIS WITH PERIVALVULAR EXTENSION

LONG-TERM ORAL SUPPRESSIVE ANTIBIOTIC THERAPY FOR PROSTHETIC VALVE ENDOCARDITIS WITH PERIVALVULAR EXTENSION

TRICUSPID VALVE INFECTIVE ENDOCARDITIS REQUIRING VALVE REPLACEMENT THREE TIMES IN AN IV DRUG USER

TRICUSPID VALVE INFECTIVE ENDOCARDITIS REQUIRING VALVE REPLACEMENT THREE TIMES IN AN IV DRUG USER

Diffuse Geometric Erosions on the Skin of a Premature Infant, Fraternal Twin Unaffected

Diffuse Geometric Erosions on the Skin of a Premature Infant, Fraternal Twin Unaffected

Outpatient parenteral antimicrobial therapy (OPAT) for aortic vascular graft infection; a five-year retrospective evaluation

ObjectivesAn estimated 1% of endovascular aneurysm repair (EVAR) devices become infected, carrying a high mortality rate. Surgical explantation is recommended and prognosis is guarded. This retrospective cohort analysis focuses on the role of outpatient parenteral antimicrobial therapy (OPAT) in the management of aortic vascular graft infections following EVAR.MethodsPatients who received OPAT for aortic graft infections (AGI) following EVAR from 2014 to 2018 inclusive were identified using the OPAT database. Clinical, microbiological and radiological data were collected. Survivors were followed up for a median of 36 months (range 25–60) after first presentation with infection. Outcomes were assessed.ResultsEleven cases with 20 OPAT episodes were identified: 10/11 male, median age 76 (IQR 71–81). Median time to presentation was 7 months (range 0–81 months) after EVAR. OPAT lead to a 55% reduction in length of hospital stay. One patient had graft explantation; four others had temporising measures. Eight of 11 were alive a median of 36 months after presentation with infection, having had a median of 2 re-treatments on OPAT (range 1–3). Seven of the eight survivors were on continuous suppressive oral antimicrobials; three were also intermittently on intravenous antibiotics for flares of infection. Patient/ infection outcomes were cure (1/11), improved (7/11), failure (3/11).ConclusionAGI following EVAR usually presents in the first year after graft deployment. OPAT has an important peri-operative role in patients suitable for curative surgery. OPAT followed by oral suppressive antimicrobial therapy can be a feasible long-term treatment for non-curative management of AGI. Survival in our cohort was longer than expected, and OPAT was feasible despite the complexity of these infections. OPAT can avoid multiple and lengthy hospital admissions and maximise time at home and quality of life in this cohort with life-limiting infection.

Neonatal Herpes Simplex Virus: The Long Road to Improved Outcomes.

Herpes simplex virus (HSV) acquired during delivery places the neonate at risk for mortality or long-term neurodevelopmental disability. Exposure generally occurs from recurrent genital herpes infection, although primary infections result in the highest risk of neonatal disease. Neonates generally present in the second or third week of life with lesions. Encephalitis with seizures indicates the presence of central nervous system involvement, and other end organs may also be impacted. Clinical suspicion for neonatal HSV infection warrants immediate initiation of appropriate antiviral therapy. In the last 50 years, antiviral therapy has progressed from agents with prohibitive toxicity or cumbersome administration to herpes virus-specific agents that dramatically improve clinical outcomes with manageable toxicity. Multicenter clinical trials have demonstrated the superiority of high-dose intravenous acyclovir for acute therapy, followed by long-term oral suppressive therapy. This work has dramatically reduced morbidity and mortality from neonatal HSV, representing the benchmark for future clinical trials in neonatal pharmacotherapy.

Irrigation, Débridement, and Implant Retention for Recurrence of Periprosthetic Joint Infection Following Two-Stage Revision Total Knee Arthroplasty: A Matched Cohort Study

BackgroundWe investigated clinical/functional outcomes and implant survivorship in patients who underwent 2-stage revision total knee arthroplasty (TKA) after periprosthetic joint infection (PJI), experienced acute PJI recurrence, and underwent irrigation, débridement, and polyethylene exchange (IDPE) with retention of stable implant. MethodsTwenty-four patients (24 knees) were identified who underwent 2-stage revision TKA for PJI, experienced acute PJI recurrence, and then underwent IDPE between 2005 and 2016 (minimum 2-year follow-up). After IDPE, intravenous antibiotics (6 weeks) and oral suppression therapy (minimum 6 months) were administered. Data were compared with 1:2 matched control group that underwent 2-stage revision TKA for chronic PJI and did not receive IDPE. ResultsAverage IDPE group follow-up was 3.8 years (range, 2.4-7.2). Reinfection rate after IDPE was 29% (n = 7): 3 of 7 underwent second IDPE (2 of 3 had no infection recurrence) and 5 (one was patient who had recurrent infection after second IDPE) underwent another 2-stage revision TKA. Control group reinfection rate was 27% (n = 13) (P = .85). For IDPE group, mean time to reinfection after 2-stage revision TKA was 4.6 months (range, 1-8 months) (patients presented with acute symptoms less than 3 weeks duration). At latest follow-up, mean Knee Society Score was 70 (range, 35-85) in IDPE group and 75 (range, 30-85) in control group (P = .53). ConclusionIDPE for acute reinfection following 2-stage revision TKA with well-fixed implants had a 71% success rate. These patients had comparable functional outcome as patients with no IDPE after 2-stage revision TKA. IDPE followed by long-term suppression antibiotic therapy should be considered in patients with acute infection and stable components.

1087. Aortic Graft Infections Caused by Propionibacterium acnes at the Minneapolis Veterans Affairs Health Care System (MVAHCS) 2007–2017

Background Propionibacterium acnes is a Gram-positive microaerophilic bacterium and part of the human skin flora. The ability of P. acnes to cause infections has been recognized, particularly in the presence of hardware. We aimed to define the frequency of P. acnes infections, with a focus on aortic graft infection.MethodsWe used microbiology laboratory records at the Minneapolis Veterans Affairs Health Care System to identify all P. acnes cultures from January 2007 to January 2017. We retrospectively reviewed all adult (≥18 years) patient’s medical records to identify associated infectious syndromes. Case definitions by the management of Aortic Graft Infection Collaboration were used to classify aortic graft infection cases.ResultsWe identified 328 positive P. acnes cultures during the study period. P. acnes was classified as a pathogen in 48 (15%), a pathogen of undetermined significance in 70 (21%), and a contaminant in 210 (64%) cases. We identified three cases aortic graft infection which accounted for (2.5%) of infections caused by P. acnes. Median age (range) at presentation was 74 years (67–83). Symptoms included pain (n = 3), fever (n = 2), and altered mental status (n = 1). None were hypotensive. All patients had at least one revision for endoleak prior to presentation. Median time from symptom onset to diagnosis was 120 days (78–140). Microbiological diagnosis was obtained by blood cultures, percutaneous peri-graft tissue aspiration, and operative culture in each patient, respectively. Infection was complicated by metastatic abscess in one patient. All cultures grew on Day 7. All patients were treated with IV ceftriaxone, and two were transitioned to life-long oral suppressive antibiotic therapy. Two patients had complete removal of infected material. No relapse was documented and survival was 100% at 1 year follow-up.ConclusionAortic graft infection is an uncommon subset of infections caused P. acnes. Clinical course is indolent and diagnosis is delayed due to nonspecific clinical presentation. In contrast to endovascular graft infection caused by other organisms, mortality is low when treated with appropriate antibiotic therapy and removal of infected material. The current laboratory practice of holding blood cultures for 5 days may need to be altered when P. acnes is a potential cause of infection.Disclosures All authors: No reported disclosures.

A Comparison of Cefazolin Versus Ceftriaxone for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia in a Tertiary Care VA Medical Center.

Cefazolin and ceftriaxone are frequently used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, especially in the realm of outpatient parenteral antimicrobial therapy. Both antimicrobials have been associated with favorable clinical outcomes for mixed MSSA infections. However, limited published data exist specifically comparing the use of these agents for the treatment of MSSA bacteremia. We conducted a retrospective cohort study of Veteran patients with MSSA bacteremia who received ≥14 days of cefazolin or ceftriaxone between 2009 and 2014. Rates of treatment failure were compared between both groups. Treatment failure was defined as therapy extension, incomplete therapy, unplanned oral suppressive therapy, relapse of infection, or hospital admission or surgery within 90 days. Out of 71 patients, 38 received treatment with cefazolin and 33 with ceftriaxone. The overall rate of treatment failure was 40.8%, with significantly more failures among patients receiving ceftriaxone (54.5% versus 28.9%; P = .029). Factors associated with treatment failure included longer duration of parenteral therapy, heart failure, and treatment in an external skilled nursing facility as compared with treatment in the Department of Veterans Affairs attached Community Living Center. Ceftriaxone had a higher rate of treatment failure than cefazolin for the treatment of MSSA bacteremia in a Veteran population. Potential reasons for this could include the higher protein binding of ceftriaxone, ultimately resulting in lower serum concentrations of free drug, or other unknown factors. Further studies are warranted to confirm these results.

Role of Suppressive Oral Antibiotics in Orthopedic Hardware Infections for Those Not Undergoing Two-Stage Replacement Surgery.

Background. The use of suppressive antibiotics in treatment of orthopedic hardware infections (OHIs), including spinal hardware infections, prosthetic joint infections, and infections of internal fixation devices, is controversial. Methods. Over a 4-year period at 2 academic medical centers, patients with OHI who were treated with debridement and retention of hardware components, with single-stage exchange, or without surgery were studied to determine whether use of oral antibiotics for at least 6 months after diagnosis impacts successful treatment of the infection at 1 year after diagnosis. Results. Of 89 patients in the study, 42 (47.2%) were free of clinical infection 1 year after initial diagnosis. Suppressive antibiotics used for at least 6 months after diagnosis was not associated with being free of clinical infection (adjusted odds ratio [aOR], 5.29; 95% confidence interval [CI], .74-37.80), but being on suppressive antibiotics at least 3 months after diagnosis was associated with being free of clinical infection (OR, 3.50; 95% CI, 1.30-9.43). Causative organisms impacted the likelihood of success; patients with methicillin-resistant Staphylococcus aureus as well as with Gram-negative rods were both less likely to have achieved clinical success at 1 year after surgery (aOR = 0.018, 95% CI = .0017-.19 and aOR = 0.20, 95% CI = .039-.99, respectively). Conclusions. Oral suppressive antibiotic therapy in treatment of OHI with retention of hardware for 3 months, but not 6 months, postdiagnosis increases the likelihood of treatment success. The organisms implicated in the infection directly impact the likelihood of treatment success.

Persistent Bloodstream Infection with P. aeruginosa in a Patient with an Aortic Root Graft and a New Diagnosis of Lung Cancer

Pseudomonas aeruginosa is the third most common gram-negative pathogen causing bloodstream infection (BSI) and is associated with an elevated mortality rate of up to 42%. The primary sources of infection are the pulmonary system, indwelling catheters, urinary tract, and soft tissue. BSI caused by vascular graft infection is 1-6% depending on the location of the graft. There is increasing prevalence of resistance of P. aeruginosa to antimicrobial agents, and oral agents are usually not considered as treatment of choice for P. aeruginosa BSI. Here, we report a case of persistent BSI with P. aeruginosa with the aortic graft as the primary source of infection. Patient did not go through aortic graft extraction due to new diagnosis of end stage lung cancer but was successfully managed by oral suppression therapy after failing a prolonged course of IV antibiotic therapy.

Diagnosis of infected total hip arthroplasty.

Despite the battery of available tests, the diagnosis of periprosthetic joint infection (PJI) remains a challenge. A comprehensive medical history and physical examination with appropriate radiographs followed by erythrocyte sedimentation rate and serum C-reactive protein are the first-line screening test for patients with suspected hip PJI. The second line of investigation of patients with abnormal serology or a strong suspicion for PJI, is joint aspiration. Aspirates should be sent for assessment of white blood cell count, polymorphonuclear percentage, leukocyte esterase strip test, and microbiology. If the first attempt fails, the joint should be re-aspirated at a different time. The International Consensus recommends against infiltration of saline or other fluids into a "dry" joint. In patients not planned for surgery but need further evaluation for PJI, a nuclear imaging study may help. In others with a planned revision surgery, intraoperative samples for frozen section and culture study are the best measures available. Treatment strategies for PJI are well established in the literature. Poor surgical candidates receive oral suppressive antibiotic therapy alone. Acute PJI, presenting within 4 weeks of the index surgery, or as a result of bacteraemia, may be treated with irrigation and debridement and implant retention. Chronic PJI, occurring more than 4 weeks after initial surgery, is treated with 1-stage or 2-stage revision arthroplasty. In some persistent infections or patients who refuse to undergo revision surgery, salvage procedures may be needed.

Safe Prevention of the Primary Cesarean Delivery

Safe Prevention of the Primary Cesarean Delivery

Staphylococcus aureus osteitis of the dens: A rare location

An immunocompetent 84-year-old woman was admitted for severe neck pain with a fever. Magnetic resonance imaging showed osteitis of the dens. She had methicillin-susceptible Staphylococcus aureus bacteremia related to a dental extraction. She then developed an infection of a hip prosthesis due to the same organism. Her treatment consisted in intravenous antibiotics followed by oral suppressive antibiotic therapy for 2years. Exchange arthroplasty was not performed given the advanced age of the patient, her unwillingness to undergo the procedure, and the risk of neurological complications during endotracheal intubation. The outcome was favorable at last follow-up more than 2years after antibiotic treatment initiation.

Acyclovir Dosing in the Neonatal Period and Beyond

You have been consulted to recommend antiviral therapy for a 3-week-old infant who presented with herpetic vesicles at 7 days of age. There has been no evidence of dissemination infection or encephalitis, and the working diagnosis is the skin-eye-mucous membrane presentation of neonatal herpes simplex infection. The infant is nearing completion of a 14-day course of intravenous acyclovir. You have asked the resident on your service to look up the dosing recommendations for oral suppressive therapy for this infant. The resident has been looking at drug dosing applications (Apps) on his smart phone for several minutes in an effort to answer this question. He looks up at you with a bewildered expression and asks, “Am I looking for something in meters squared or milligrams per kilo? Are the doses the same for herpes simplex and varicella? What is the evidence for doing this, anyway?”

Can Infection Associated With Rib Distraction Techniques Be Managed Without Implant Removal?

Retrospective clinical cohort study of infections in patients treated using rib distraction techniques. To determine if patients with early onset spinal deformity, who develop infection around their rib distraction implant, can be successfully managed without implant removal. Vertical Expandable Prosthetic Titanium Rib (VEPTR) has gained wide acceptance for the management of progressive complex spinal deformity in children. Many children in this population have significant comorbidities and low body mass index putting them at high risk for infection. Typically, the protocol for treating all but early infection recommends implant removal. The purpose of this study is to determine if a VEPTR infection can be managed effectively without implant removal. This is an institutional review board-approved retrospective review of medical records of all patients who had VEPTR procedures and developed infections at PCMC from 2002 to 2008. Ninety-seven patients underwent 678 VEPTR procedures. Nineteen infections developed in 16 patients, with a 2% overall rate of infection per procedure. The average body mass index (16.2) and absolute neutrophil count (8.2) were predictably low for this population. The diagnosis was varied. Infection was associated with initial implantation (31%), expansion (47%), exchange (5%), and revision (21%). Seventeen of 19 infections followed a wound dehiscence. Thirteen infections were classified as superficial and six deep. All patients were treated with initial irrigation and debridement (I&D) and intravenous antibiotics. The average duration of intravenous therapy was 58 days, followed by oral suppressive therapy for 34 days (2-126). Three patients required more than one debridement to control the infection (range, 2-4 I&D). No patient has required VEPTR removal to resolve the infection. These data suggest that infections involving VEPTR instrumentation without fusion procedures can be effectively managed without implant removal. Nutrition and improved soft tissue management may be significant in reducing the incidence of infection in this patient population.

Congenital herpes simplex II (HSV-2) with limb abnormalities

Background and aimsThe classical presentation of congenital HSV infection is grouped vesicles on an erythematous base and/or widespread skin erosions. Associated limb malformations have been reported only once.MethodsWe present a...

Novel Mutations in a Patient Isolate of Streptococcus agalactiae with Reduced Penicillin Susceptibility Emerging after Long-Term Oral Suppressive Therapy

Penicillin nonsusceptibility has been demonstrated in group B streptococci (GBS), but there is limited information regarding mechanisms of resistance. We report a case of GBS with reduced susceptibility to penicillin emerging after long-term suppressive oral penicillin therapy for a prosthetic joint infection. Molecular characterization of the isolate before and after long-term penicillin therapy revealed 5 mutations in the ligand-binding regions of PBP1a, -2a, and -2x not previously reported in GBS.

Prosthetic hip infection due to Cryptococcus neoformans: case report

Prosthetic joint infections due to Cryptococcus neoformans have not been described before. We report a case of a prosthetic hip joint infection due to C. neoformans. An 84-year-old man with chronic lymphocytic leukemia presented with progressive left groin pain and fever. There was radiographic evidence of prosthesis loosening, and an aspirate of the left hip joint grew C. neoformans. The patient was treated with amphotericin B with good initial symptomatic response. The patient elected not to undergo revision arthroplasty, and oral suppressive therapy with fluconazole was initiated. After 10 months of fluconazole therapy, the prosthesis was removed secondary to pain and increased instability of the implant. Despite excellent penetration of fluconazole into the joint fluid and reports of successful outcome in patients with native joint cryptococcal infections as well as prosthetic joint infections due to Candida spp., suppressive fluconazole therapy failed. The failure may have been due to an unfavorable interaction between the organism and immune mechanism as well as reduced activity of fluconazole in biofilm.