Fungal Prosthetic Joint Infection: A Case Series and Review of the Literature.

INTRODUCTION: Fungal prosthetic joint infections comprise less than 1% of prosthetic joint infections. Thus, little is known regarding optimal management. This study aims to characterize the microbiology, surgical and medical management, and outcomes for these complex infections. The objectives of this study were to assess the impact of surgical approach, antifungal treatment, fungal species, and time to onset of infection from initial surgery on patient outcomes. METHODS: A retrospective record review over 12 years was performed in two health systems that included patients with a deep culture positive for a fungal isolate and the presence of a prosthetic joint. A literature review was performed using the same inclusion criteria. A total of 289 cases were identified and analyzed. RESULTS: Candida was the most common isolate, and a two-stage revision was the most commonly employed surgical modality. The type of surgical intervention had a statistically significant relationship with outcome (P = 0.022). CONCLUSIONS: Two-stage revision with extended antifungal therapy is preferred in these infections due to higher rates of positive outcomes.

Prosthetic joint infections may be caused by fungal organisms, but as this is rare, it is not known how to best treat these infections. This study explores the types of fungal organisms involved in these infections, options for surgical and medical treatment, and patient outcomes. We analyzed records over 12 years at two health systems and the currently published works on this topic. A total of 289 records were analyzed. The fungus Candida was the most common infectious cause, and a two-stage revision surgery was most commonly performed. We found that the type of surgical intervention was correlated with the patient outcome and that two-stage revision with a long course of antifungal medications is preferred in these infections.

The Role of Community Pharmacies in Providing Access to HIV Post-exposure Prophylaxis (PEP).

HIV affects an estimated 1.2 million individuals in the United States and is disproportionately concentrated among African Americans, Latinos, and people of multiple races. Post-exposure prophylaxis (PEP) substantially decreases HIV transmission when started within 72 h after exposure, but problems of accessibility have hindered its widespread usage in communities at risk for HIV infection. Pharmacy-initiated PEP access was first permitted in New York City in 2017, allowing pharmacists to provide a 7-day supply of PEP without a prescription for consumers at high risk for HIV infection. It was expected that the broad reach and accessibility of community pharmacies would increase timely access to PEP for all individuals, especially those who already face significant barriers to accessing the healthcare system. Since then, eleven other states have followed suit and expanded the scope of outpatient pharmacy practice in order to increase the availability of HIV PEP but prescribing laws in over 75% of the US have not been changed. Much of the existing literature on HIV prevention focuses on PrEP access barriers with limited information on PEP access in the US. In this paper, we review the current status of pharmacist-initiated PEP in the US as part of the End the HIV Epidemic (EHE) initiative.

Serratia Marcescens, a Rare and Devastating Cause of Endocarditis: A Case Report and Review of the Literature.

Serratia marcescens is a gram-negative bacillus that is an opportunistic agent in respiratory tract infections, urinary tract infections, and septicemia. It is rarely a cause of infective endocarditis, but in cases of endocarditis, it follows a rapid and devastating course. A previously healthy female in her mid-50s presented with fever, abdominal pain, right lower extremity pain, and diarrhea. Blood cultures were positive for S. marcescens , and additional evaluation revealed infarction in the spleen and kidneys, raising concern for endocarditis with associated embolic phenomena. The patient was subsequently found to have an embolus in the right popliteal artery and underwent a right popliteal thromboembolectomy. Antimicrobial therapy with cefepime and gentamicin was begun. A transesophageal echocardiogram revealed a large, mobile mitral valve vegetation. Care was complicated by intracranial hemorrhage, and the decision was made to withdraw care. A review of the databases Embase and PubMed revealed 63 additional cases of S. marcescens endocarditis. Analysis of these cases demonstrated a preponderance of aortic and mitral valve involvement, not tricuspid valve involvement, despite a risk factor of intravenous drug use in over 60% of cases. Mortality was 50%, and sequelae such as congestive heart failure and renal insufficiency occurred in the majority of survivors. In conclusion, S. marcescens is a rare but devastating cause of endocarditis with a primary risk factor of intravenous drug use but with a predilection for left-sided valvular lesions, not right-sided lesions.

Is Long-acting Cabotegravir a Pre-exposure Prophylaxis Option for Women of Childbearing Potential?

Long-acting cabotegravir (CAB-LA) provides an exciting new option for pre-exposure prophylaxis (PrEP) in multiple populations. In this Perspective, we consider the unique pharmacokinetics of CAB-LA and the potential impact on the prescribing of CAB-LA, specifically in cis-women of reproductive potential.

Pleural Effusion/Empyema With Mycobacterium kansasii.

Mycobacterium kansasii is a nontuberculous mycobacterium that causes pulmonary symptoms, commonly associated with underlying conditions, including malignancy, prior transplant, and HIV. However, rarely does Mycobacterium kansasii present with pleural effusion. We present a case of a 56-year-old female who presented with dyspnea and chest pain, and sputum culture was positive for acid-fast bacilli. A CT scan revealed a left-sided pleural effusion. Based on a thorough review of the literature using Embase and PubMed, we found that only 22 cases of a Mycobacterium kansasii pleural effusion have been reported. We provide a discussion on maintaining a broad differential in the treatment of immunocompromised individuals with Mycobacterium infection.

Dynamic modeling of hospitalized COVID-19 patients reveals disease state-dependent risk factors.

OBJECTIVE: The study sought to investigate the disease state-dependent risk profiles of patient demographics and medical comorbidities associated with adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. MATERIALS AND METHODS: A covariate-dependent, continuous-time hidden Markov model with 4 states (moderate, severe, discharged, and deceased) was used to model the dynamic progression of COVID-19 during the course of hospitalization. All model parameters were estimated using the electronic health records of 1362 patients from ProMedica Health System admitted between March 20, 2020 and December 29, 2020 with a positive nasopharyngeal PCR test for SARS-CoV-2. Demographic characteristics, comorbidities, vital signs, and laboratory test results were retrospectively evaluated to infer a patient's clinical progression. RESULTS: The association between patient-level covariates and risk of progression was found to be disease state dependent. Specifically, while being male, being Black or having a medical comorbidity were all associated with an increased risk of progressing from the moderate disease state to the severe disease state, these same factors were associated with a decreased risk of progressing from the severe disease state to the deceased state. DISCUSSION: Recent studies have not included analyses of the temporal progression of COVID-19, making the current study a unique modeling-based approach to understand the dynamics of COVID-19 in hospitalized patients. CONCLUSION: Dynamic risk stratification models have the potential to improve clinical outcomes not only in COVID-19, but also in a myriad of other acute and chronic diseases that, to date, have largely been assessed only by static modeling techniques.

Effects of antibiotic treatment on microbiota, viral transmission and viral pathogenesis of MoMuLV ts1 infected BALB/c mice.

The effects of normal and altered intestinal microbiota on murine retroviral transmission via the gastrointestinal tract (GIT) are diverse. The role of orally administered antibiotic treatment (ABX) on viral transmission, GIT microbial dysbiosis and subsequent pathogenesis of Moloney Murine Leukemia virus-temperature sensitive 1 (ts1) on BALB/c mice were studied. BALB/c mice were divided into four groups: ABXts1-Treatment/Infection;ABX-Treatment/No infection;ts1-No treatment/Infection;Ctrl (control)-No treatment/No infection. ABXts1 and ABX groups showed a significant phylogenetic shift (ANOSIM p-value = 0.001) in alpha and beta diversity comparisons for microbial community composition compared to Ctrl group. Mice in the ABXts1 and ABX groups showed megacolon compared to ts1 and Ctrl groups; ABXts1 and ts1 groups showed hepatosplenomegaly, thymus enlargement, and mesenteric lymphadenopathy compared to ABX and Ctrl groups. Ctrl group had no abnormal manifestations. ABX treatment and ts1 infection uniquely affect microbial community when compared to control: ABXts1 and ABX groups significantly reduce microbiome diversity by over 80% and ts1 group by over 30%. ABXts1 and ts1 groups' viral load and clinical manifestations of infection were comparable; antibiotic treatment did not notably affect ts1 infection. Transmission and pathophysiology of ts1 infection were not significantly altered by the microbial composition of the GI tract, but ts1 viral infection did result in microbial dysbiosis independent of antibiotic treatment.

Budget constrained machine learning for early prediction of adverse outcomes for COVID-19 patients.

The combination of machine learning (ML) and electronic health records (EHR) data may be able to improve outcomes of hospitalized COVID-19 patients through improved risk stratification and patient outcome prediction. However, in resource constrained environments the clinical utility of such data-driven predictive tools may be limited by the cost or unavailability of certain laboratory tests. We leveraged EHR data to develop an ML-based tool for predicting adverse outcomes that optimizes clinical utility under a given cost structure. We further gained insights into the decision-making process of the ML models through an explainable AI tool. This cohort study was performed using deidentified EHR data from COVID-19 patients from ProMedica Health System in northwest Ohio and southeastern Michigan. We tested the performance of various ML approaches for predicting either increasing ventilatory support or mortality. We performed post hoc analysis to obtain optimal feature sets under various budget constraints. We demonstrate that it is possible to achieve a significant reduction in cost at the expense of a small reduction in predictive performance. For example, when predicting ventilation, it is possible to achieve a 43% reduction in cost with only a 3% reduction in performance. Similarly, when predicting mortality, it is possible to achieve a 50% reduction in cost with only a 1% reduction in performance. This study presents a quick, accurate, and cost-effective method to evaluate risk of deterioration for patients with SARS-CoV-2 infection at the time of clinical evaluation.

Time between diagnosis and achievement of virologic suppression in people living with HIV.

PURPOSE: Data support the individual and public health advantages of shortened time intervals between HIV diagnosis, initiation of antiretroviral therapy (ART), and virologic suppression. The time from HIV diagnosis to linkage to care, initiation of ART, and virologic suppression was evaluated in newly diagnosed, ART-naive individuals after structured programmatic changes were implemented to reduce time to virologic suppression (TVS). METHODS: The retrospective cohort included newly diagnosed, ART-naive adult patients receiving care in a Midwestern Ryan White Clinic. Study periods were between January 1, 2015, and December 31, 2015 (delayed treatment group) and January 1, 2017, and December 31, 2017 (rapid treatment group). Changes during the intervention time period were related to access to care and ART. The primary outcome of time from HIV diagnosis to virologic suppression was compared between the groups. Secondary outcomes included the time from diagnosis to linkage to care and the time to initiation of ART. RESULTS: Twenty-four and 35 individuals were included in the control and intervention groups, respectively. Median (interquartile range) time from diagnosis to viral suppression was 137 (77-318) days in the delayed treatment group vs 76.5 (51-151) days in the rapid treatment group (P = 0.021). Time from diagnosis to first clinic visit remained similar (median of 13.5 vs 15 days, P = 0.859), while time from first clinic visit to initiation of ART decreased significantly (median of 15 vs 0 days, P < 0.001). CONCLUSION: Time from first clinic visit to ART initiation was significantly shortened in this intervention and was the driving force to decreasing TVS. Additional research into barriers impacting time from diagnosis to linkage to care are needed to further shorten TVS.

Use of an On-Site Outpatient Pharmacy for Acquisition of Antiretroviral Medications Compared to Off-Site Pharmacy Options: Impact on Retention in Care and Clinical Outcomes in People Living With HIV.

BACKGROUND: Few published studies have examined the relationship between pharmacy location and retention in care or clinical outcome in people living with HIV (PLWH). OBJECTIVE: The study purpose was to determine whether using an on-site/in-clinic pharmacy to obtain antiretroviral therapy increased retention in care and virologic suppression rates. METHODS: PLWH attending a Ryan White outpatient clinic in an academic center were matched based on age and insurance. Rates of retention in care ( ≥2 medical visits/calendar year) were assessed between patients using a pharmacy on-site in the clinic versus patients use off-site pharmacy options. Virologic suppression [viral load(VL)<200 copies/mL], completing ≥2 VL, and CD4 count were compared between pharmacy types. RESULTS: 137 on-site pharmacy patients and 274 off-site pharmacy patients met inclusion and matching criteria. 91.2% of on-site pharmacy users attended ≥2 clinic visits compared to 83.2% of off-site pharmacy users (P = .0275) and were approximately twice as likely to complete ≥2 clinic visits (odds ratio: 2.032; 1.071-3.857). A similar proportion of the on-site pharmacy group achieved virologic suppression compared to the off-site pharmacy group (92.7% vs 89.1%; P = .239, respectively). CONCLUSIONS: On-site pharmacies may provide an opportunity to positively impact retention in care and clinical outcomes for PLWH.

Efficacy of tocilizumab in COVID-19: A systematic review and meta-analysis.

The efficacy of tocilizumab (TOC), monoclonal antibody against interleukin-6 (IL-6) receptor, in patients with coronavirus disease-2019 (COVID-19) patients has led to conflicting results. We performed a systematic review and meta-analysis to compare the efficacy of addition of TOC to standard of care (SOC) versus SOC in patients with COVID-19. We performed a comprehensive literature search of PubMed, Embase, Web of Science, WHO COVID, LitCOVID, and Cochrane databases. Pooled outcomes (overall mortality, need for mechanical ventilation, intensive care unit admission, and secondary infections) were compared using DerSimonian-Laird/Random-effects approach. Risk difference (RD), confidence interval (CI), and p values were generated. A total of 23 studies with 6279 patients (1897 in TOC and 4382 in SOC group, respectively) were included. The overall mortality was lower in TOC group compared to SOC group (RD: -0.06; CI: -0.12 to -0.01; p = .03). Subgroup analysis including studies with only severe cases revealed lower mortality (RD: -0.12; CI: -0.18 to -0.06; p < .01) and need for mechanical ventilation (RD: -0.11; CI: -0.19 to -0.02; p = .01) in TOC group compared to SOC group. The addition of TOC to SOC has the potential to reduce mortality and need for mechanical ventilation in patients with severe COVID-19. Randomized controlled trials are needed to validate this.

Clinical Characteristics and Outcomes of Staphylococcus lugdunensis Prosthetic Joint Infections: A Multicenter Retrospective Analysis.

Staphylococcus lugdunensis has been increasingly recognized as a cause of serious infections, particularly prosthetic joint infections (PJIs). The aim of this study was to describe the clinical characteristics, treatments, and outcomes of S lugdunensis PJIs. This was a retrospective multicenter study of consecutive adult patients with S lugdunensis PJIs from January 2007 through December 2017; 28 patients met inclusion criteria. The knee was the most commonly affected joint (67.9%), followed by the hip (25%). Clinical and microbiologic characteristics, treatment modalities, and outcomes were evaluated. Thirteen (46.4%) patients had two-stage revision, 9 (32.1%) had debridement with or without revision, 5 (21.4%) had no surgical intervention, and 1 (3.6%) had one-stage revision. Twenty-four (85.7%) patients had monomicrobial infection with S lugdunensis, whereas 4 had polymicrobial. Two patients had concomitant bacteremia. All isolates, except 1, were susceptible to oxacillin. Three patients with no surgical intervention received oral antibiotics, 2 were not treated, and 1 was discharged to hospice. Relapse was observed in 2 of 13 (15%) patients who had two-stage revision, 4 of 9 (44%) who had debridement, and 6 of 6 (100%) who had no surgical intervention or one-stage revision regardless of antibiotic treatment regimen. There was a significant difference in cure rate for patients who underwent two-stage revision compared with other treatment modalities (85% vs 33%, P=.009). Appropriate management of S lugdunensis PJI includes both aggressive surgical treatment and a prolonged course of antibiotics and is associated with excellent clinical response. Regardless of route or duration of antibiotic therapy, relapse is high for patients not treated with two-stage revision. [Orthopedics. 2020;43(6):345-350.].

Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation.

BACKGROUND: Limited data exist on the use of a boosted protease inhibitor plus <2 active nucleoside/nucleotide reverse transcriptase inhibitors without use of additional classes of antiretroviral (ARV) therapy in treatment-experienced patients with background resistance. OBJECTIVE: To evaluate clinical outcomes in HIV-infected patients harboring single- or multiclass resistant virus and receiving once-daily tenofovir/emtricitabine (TDF/FTC) plus darunavir/ritonavir (DRV/r) administered for >24 weeks. METHODS: This was a single-center chart review of HIV-infected patients receiving daily TDF/FTC plus DRV/r and identified with resistant virus (including, but not limited to, an M184V/I). The primary outcome was HIV viral load (VL) <200 copies/mL (cp/mL) at last measurement. Additional end points included virological rebound (VR), resuppression, or failure (VF); VL <40 cp/mL at last measurement; and development of additional mutations. RESULTS: Of 171 eligible patients, 32 were included in the study and received DRV 800 mg/r 100 mg daily with fixed-combination TDF/FTC. All patients had a baseline M184V/I mutation, with 10 (31%) having resistance to TDF; 27 (84%) achieved a VL <200 cp/mL, and 25(78%) had a VL <200 cp/mL at the last reading; 22 (69%) achieved a VL <40 cp/mL. VF occurred in 6/32 (19%) patients and VR in 1/32 (3%) patients. Conclusion and Relevance: Although providing a regimen containing ≤2 active drugs, the use of once-daily DRV/r plus TDF/FTC in treatment-experienced patients with single-/multiclass resistant virus resulted in virological suppression in more than three-fourths of patients. These retrospective data suggest that despite the presence of an M184V/I, this combination may be an option in patients seeking a once-daily ARV therapy to improve adherence.

Hemophagocytic Lymphohistiocytosis in the Elderly.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of massive, dysregulated cytokine release and secondary multiorgan failure and is associated with high mortality. Primary HLH occurs predominately in infants and young children with a genetic predisposition. Acquired HLH is less well characterized and usually occurs in younger adults in the setting of severe inflammation triggered by infection or malignancy. Little is known about the disease in elderly. We report 3 patients >50 years old who presented with multiorgan failure and shock without an identifiable source and were ultimately diagnosed with acquired HLH. We performed a literature review of HLH in adults >50 years of age and identified an additional 68 cases. Mean age was 62 years, with male predominance. Most cases were triggered by infection (49%) followed by malignancy (27%). Nineteen patients were treated with the HLH-94 protocol, 11 received corticosteroids and the remainder received non-HLH specific interventions. Overall mortality was 62%.

Analysis of a ten step protocol to decrease postoperative spinal wound infections.

AIM: To define a ten-step protocol that reduced the incidence of surgical site infection in the spine surgery practice of the senior author and evaluate the support for each step based on current literature. METHODS: In response to unexplained increased infection rates at our institution following spine surgery, a ten-step protocol was implemented: (1) preoperative glycemic management based on hemoglobin A1c (HbA1c); (2) skin site preoperative preparation with 2% chlorhexidine gluconate disposable cloths; (3) limit operating room traffic; (4) cut the number of personnel in the room to the minimum required; (5) absolutely no flash sterilization of equipment; (6) double-gloving with frequent changing of outer gloves; (7) local application of vancomycin powder; (8) re-dosing antibiotic every 4 h for prolonged procedures and extending postoperative coverage to 72 h for high-risk patients; (9) irrigation of subcutaneous tissue with diluted povidone-iodine solution after deep fascial closure; and (10) use of DuraPrep skin preparation at the end of a case before skin closure. Through an extensive literature review, the current data available for each of the ten steps was evaluated. RESULTS: Use of vancomycin powder in surgical wounds, routine irrigation of surgical site, and frequent changing of surgical gloves are strongly supported by the literature. Preoperative skin preparation with chlorhexidine wipes is similarly supported. The majority of current literature supports control of HbA1c preoperatively to reduce risk of infection. Limiting the use of flash sterilization is supported, but has not been evaluated in spine-specific surgery. Limiting OR traffic and number of personnel in the OR are supported although without level 1 evidence. Prolonged use of antibiotics postoperatively is not supported by the literature. Intraoperative use of DuraPrep prior to skin closure is not yet explored. CONCLUSION: The ten-step protocol defined herein has significantly helped in decreasing surgical site infection rate. Several of the steps have already been shown in the literature to have significant effect on infection rates. As several measures are required to prevent infection, instituting a standard protocol for all the described steps appears beneficial.

Evaluation of Serum Creatinine Changes With Integrase Inhibitor Use in Human Immunodeficiency Virus-1 Infected Adults.

This retrospective chart review evaluated changes in serum creatinine and creatinine clearance (CrCl) after initiation of an integrase inhibitor (INSTI)-based regimen as initial treatment in human immunodeficiency virus-infected adults. Serum creatinine and CrCl changes were similar to those seen in clinical trials for INSTIs. No renal-related serious adverse events or discontinuations occurred.

Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.

Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure.