Effective use of a two-dose regimen of dalbavancin to treat prosthetic joint infections and spinal hardware infections.

PURPOSE: Dalbavancin is an attractive antibiotic for the treatment of Gram-positive musculoskeletal infections given its long half-life and prolonged duration in cortical bones. For certain patient populations compliance with antibiotic regimens can be problematic. Therefore, the purpose of this study was to assess the effectiveness, tolerance, and compliance of treating prosthetic joint and spinal hardware infections with a unique two-dose regimen of dalbavancin. METHODS: Identification of patients that had prosthetic joint infections and spinal hardware infections from January 1, 2017, through December 31, 2021, that had received a two-dose regimen of dalbavancin for these infections was conducted. Patient demographics, infection recurrence, compliance and adverse drug reactions to the two-dose regimen of dalbavancin were recorded. Furthermore, preserved clinical isolates from these infections were assessed for susceptibility to dalbavancin with microbroth dilutions. RESULTS: All patients were fully compliant with the two dose dalbavancin regimen and no patient had any adverse reactions to the two-dose dalbavancin regimen. Thirteen of fifteen patients (85.7%) have not had any recurrence of their infections and all preserved clinical isolates showed susceptibility to dalbavancin. DISCUSSION: The two-dose regimen of dalbavancin is an effective and attractive option in treating prosthetic joint and spinal hardware infections to forgo long term central venous access and ensure compliance. However, the use of rifampin and suppression antibiotics still needs to be considered when treating these infections. Nonetheless this study supports that a two-dose dalbavancin regimen is a viable alternative in certain clinical settings and consideration for a randomized controlled clinical trial should be entertained to prove its non-inferiority to conventional treatments.

Predictors of Nonadherence Among Patients With Infectious Complications of Substance Use Who Are Discharged on Parenteral Antimicrobial Therapy.

Background: The management of invasive infections related to substance use disorder (SUD) needing parenteral antimicrobial therapy is challenging and may have poor treatment outcomes including nonadherence and lack of completion of parenteral antimicrobial therapy. Methods: In this retrospective cohort of 201 patients with invasive infections related to SUD, we looked at frequency and determinants of unfavorable outcomes including nonadherence. Results: Seventy-nine percent of patients with SUD-related infection completed parenteral antibiotic therapy in skilled nursing facilities. A total of 21.5% of patient episodes had documentation of nonadherence. Nonadherence was higher in patients with active injection drug use (IDU) (28.5% versus 15% in non IDU; adjusted odds ratio [OR] 2.36; 95% confidence interval [CI], 1.1-5.5; P = .024), patients with active SUD in the prior year (24.5% vs 11%, P = .047), patients with use of more than 1 illicit substance (30.3% vs 17%, P = .031), as well as in people experiencing homelessness (32.8% vs 15.7% in stably housed, P = .005). In a multivariate model, nonadherence was significantly associated with IDU (OR, 2.38; 95% CI, 1.03-5.5) and homelessness (OR, 2.25; 95% CI, 1.01-4.8) Medication for opioid use disorder was prescribed at discharge in 68% of overall cohort and was not associated with improved outcomes for any of the above groups. Conclusions: Nonadherence to parenteral antimicrobial therapy is high in the most vulnerable patients with unstable high-risk SUD and adverse social determinants of health.

Severe Infective Endocarditis Caused by Bartonella rochalimae.

A 22-year-old man from Guatemala sought care for subacute endocarditis and mycotic brain aneurysm after living in good health in the United States for 15 months. Bartonella rochalimae, a recently described human and canine pathogen, was identified by plasma microbial cell-free DNA testing. The source of infection is unknown.

Single-Agent and Fixed-Dose Combination HIV-1 Protease Inhibitor Drugs in Fission Yeast (Schizosaccharomyces pombe).

Successful combination antiretroviral therapies (cART) eliminate active replicating HIV-1, slow down disease progression, and prolong lives. However, cART effectiveness could be compromised by the emergence of viral multidrug resistance, suggesting the need for new drug discoveries. The objective of this study was to further demonstrate the utility of the fission yeast cell-based systems that we developed previously for the discovery and testing of HIV protease (PR) inhibitors (PIs) against wild-type or multi-PI drug resistant M11PR that we isolated from an infected individual. All thirteen FDA-approved single-agent and fixed-dose combination HIV PI drugs were tested. The effect of these drugs on HIV PR activities was tested in pure compounds or formulation drugs. All FDA-approved PI drugs, except for a prodrug FPV, were able to suppress the wild-type PR-induced cellular and enzymatic activities. Relative drug potencies measured by EC50 in fission yeast were discussed in comparison with those measured in human cells. In contrast, none of the FDA-approved drugs suppressed the multi-PI drug resistant M11PR activities. Results of this study show that fission yeast is a reliable cell-based system for the discovery and testing of HIV PIs and further demonstrate the need for new PI drugs against viral multi-PI resistance.

Potential Use of Adjuvant Bacteriophage Therapy With Debridement, Antibiotics, and Implant Retention Surgery to Treat Chronic Prosthetic Joint Infections.

The number of arthroplasties conducted annually continues to increase; however, approximately 1%-2% of all knee and hip arthroplasties will become infected. These prosthetic joint infections are costly, difficult to treat, and cause significant morbidity and mortality as a direct result of conventional surgical and medical managements. In this perspective, we discuss factors that make these infections arduous to treat as well as the potential use of adjuvant bacteriophage therapy with debridement, antibiotics, and implant retention surgery to cure these infections without removing the infected prosthesis. We also provide rationale as to why future clinical trials evaluating this novel therapeutic will need to be designed as noninferiority trials, and we compare this approach to 2-stage revision surgery. If bacteriophage therapy continues to show effectiveness, this could revolutionize the treatment of prosthetic joint infections and pioneer new treatments for similar infections.

Early Use of the Palliative Approach to Improve Patient Outcomes in HIV Disease: Insights and Findings From the Care and Support Access (CASA) Study 2013-2019.

Young men of color who have sex with men (yMSM) living with human immunodeficiency virus (HIV) in syndemic environments have been difficult-to-retain in care resulting in their being at-risk for poor health outcomes despite availability of effective once-daily antiretroviral treatment (ART). Multiple methods have been implemented to improve outcomes for this cohort; none with sustainable results. Outpatient HIV staff themselves may be a contributing factor. We introduced multidisciplinary staff to the concept of using a palliative approach early (ePA) in outpatient HIV care management to enable them to consider the patient-level complexity of these young men. Young MSM (18-35 years of age) enrolled in and cared for at the intervention site of the Care and Support Access Study (CASA), completed serial surveys over 18 months. Patients' Global and Summary quality of life (QoL) increased during the study at the intervention site (IS) where staff learned about ePA, compared with patients attending the control site (CS) (p=.021 and p=.018, respectively). Using serial surveys of staff members, we found that in the era of HIV disease control, outpatient staff are stressed more by environmental factors than by patients' disease status seen historically in the HIV epidemic. A Community Advisory Panel of HIV stakeholders contributed to all phases of this study and altered language used in educational activities with staff members to describe the patient cohort.

Change in hospital antibiotic use and acquisition of multidrug-resistant gram-negative organisms after the onset of coronavirus disease 2019.

Interrupted time series segmented regression was conducted to trend antibiotic use and multidrug-resistant gram-negative (MDRGN) acquisition relative to COVID-19 in an academic hospital. Total antibiotic use and antibiotic use related to pneumonia was higher in the period after the onset of COVID-19 compared to the similar calendar period in 2019. Furthermore, MDRGN acquisition increased 3% for every increase in positive COVID-19 tests per week.

Temperature, humidity, and latitude analysis to predict potential spread and seasonality for COVID-19.

Background: A significant number of infectious diseases display seasonal patterns in their incidence, including human coronaviruses. Betacoronaviruses such as MERS-CoV and SARS-CoV are not thought to be seasonal. Methods: We examined climate data from cities with significant community spread of COVID-19 using ERA-5 reanalysis, and compared to areas that are either not affected, or do not have significant community spread. Results: To date, Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, has established significant community spread in cities and regions along a narrow east west distribution roughly along the 30-50° N' corridor at consistently similar weather patterns consisting of average temperatures of 5-11°C, combined with low specific (3-6 g/kg) and absolute humidity (4-7 g/m3). There has been a lack of significant community establishment in expected locations that are based only on population proximity and extensive population interaction through travel. Conclusions and Relevance: The distribution of significant community outbreaks along restricted latitude, temperature, and humidity are consistent with the behavior of a seasonal respiratory virus. Additionally, we have proposed a simplified model that shows a zone at increased risk for COVID-19 spread. Using weather modeling, it may be possible to predict the regions most likely to be at higher risk of significant community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19).

Importance: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies. Objective: To examine the association of climate with the spread of COVID-19 infection. Design, Setting, and Participants: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020. Main Outcomes and Measures: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis. Results: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30° N to 50° N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 °C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m3). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8° N) had 3136 deaths and 80 757 cases, Moscow, Russia (56.0° N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2° N), had 0 deaths and 31 cases. Conclusions and Relevance: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

Dalbavancin Use in Vulnerable Patients Receiving Outpatient Parenteral Antibiotic Therapy for Invasive Gram-Positive Infections.

INTRODUCTION: Dalbavancin is approved for acute bacterial skin and skin structure infections (ABSSSIs) but offers a potential treatment option for complicated invasive gram-positive infections. Importantly, dalbavancin's real benefits may be in treating complicated infections in vulnerable patient populations, such as persons who inject drugs (PWID). METHODS: A multicenter retrospective analysis was performed from March 2014 to April 2017 to assess 30- and 90-day clinical cure and adverse drug events (ADEs) in adult patients who received ≥ 1 dose of dalbavancin for a non-ABSSSI indication. RESULTS: During the study period, 45 patients received dalbavancin, 28 for a non-ABSSSI indication. The predominant infections treated included osteomyelitis (46%), endovascular infection (25%) and uncomplicated bacteremia (14%). Half of the patients had positive Staphylococcus aureus in cultures, 29% methicillin resistant and 21% methicillin susceptible. Most patients were prescribed dalbavancin as sequential treatment with a median of 13.5 days of prior antibiotic therapy. The most common reason for choosing dalbavancin over standard therapy use was PWID (54%). Seven patients were lost to follow-up at day 30. Of the remaining evaluable patients, 30-day clinical cure was achieved in 15/21 (71%) patients. The most common reason for failure was lack of source control (4/6, 67%). At day 90, relapse occurred in two patients. Three patients had a potential dalbavancin-associated ADE: two patients with renal dysfunction and one patient with pruritus. CONCLUSIONS: This study demonstrates a possible role for dalbavancin in the treatment of non-ABSSSI invasive gram-positive infections in select vulnerable OPAT patients.

HIV Viral Dynamics of Lopinavir/Ritonavir Monotherapy as Second-Line Treatment: A Prospective, Single-Arm Trial.

BACKGROUND: Characterizing viral response to lopinavir/ritonavir (LPV/r) monotherapy as second-line treatment may guide recommendations for resource-limited settings (RLS). METHODS: We conducted a 48-week prospective, single-arm study of LPV/r monotherapy in patients failing first-line therapy in Nigeria. The primary outcome was sustained HIV-1 viral load (VL) <400 copies/mL at 48 weeks. RESULTS: Of 30 enrolled patients, 28 (93%) achieved viral suppression on LPV/r, while 29 (96%) experienced low-level viremia. At 48 weeks, 9 (30%) met the primary outcome of sustained viral suppression; 14 (47%) patients were suppressed on LPV/r in a snapshot analysis. Detectable VLs at 12 and 24 weeks were strongly associated with treatment failure at 48 weeks. New resistance mutations were not detected. The trial was stopped early due to treatment failure. CONCLUSION: In this study, the rate of virologic failure among patients on a second-line lopinavir monotherapy regimen was relatively high and predicted by early detectable viremia. However, no LPV/r-associated resistance mutations were detected despite fluctuating low-level viremia, demonstrating the high genetic barrier to resistance of the protease inhibitor class which could be useful in RLS.

Epidemiology of blood stream infection in adult extracorporeal membrane oxygenation patients: A cohort study.

PURPOSE: The purpose of our study was to characterize the epidemiology of blood stream infection (BSI) in adult extracorporeal membrane oxygenation (ECMO) patients at a single tertiary care academic medical center with standardized post-cannulation antibiotic prophylaxis practices. METHODS: A single-center retrospective cohort study was performed over a five-year period. BSI incidence was characterized and patients who developed BSI during ECMO were compared with those who did not. RESULTS: Nineteen of 145 VV ECMO patients (13.1%) developed BSI while 7 of 123 VA ECMO patients (5.7%) developed BSI. When accounting for total ECMO days, the incidence rate was 8 BSIs per 1,000 ECMO days for both VV and VA ECMO patients. VV ECMO patients with BSI had longer ECMO runs and more red blood cell transfusion (both p<0.05). VA ECMO patients who developed BSI had longer ECMO runs and more platelet transfusion (both p<0.05). In VV ECMO patients there was an association between renal failure and BSI and in VA ECMO patients there was an association between hepatic failure and BSI. CONCLUSIONS: BSIs are common in ECMO patients even with post-cannulation antimicrobial prophylaxis and are associated with ECMO duration, blood transfusion, and organ failure. Further work is needed to clarify the optimal duration and type of antimicrobial prophylaxis, as well as surveillance strategies for BSIs during adult ECMO.

Decontamination and Lung Transplantation of a Patient With Cystic Fibrosis With Resistant Infections.

We describe the use of a decontamination protocol that allowed for successful lung transplantation in a patient with cystic fibrosis with necrotizing pneumonia from highly antibiotic-resistant pathogens (Burkholderia and Psuedomonas species). This strategy may allow for successful lung transplantation in patients with cystic fibrosis with multidrug-resistant infections previously considered nontransplantable.

Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected recipients.

BACKGROUND: Protease inhibitors (PI) pose a challenge post-transplant due to significant drug interactions with calcineurin inhibitors, prompting many clinicians to convert patients to non-interacting regimens prior to transplant. The purpose of this study was to examine the impact of PI-based regimens on graft outcomes in HIV-infected renal transplant recipients. METHODS: In this retrospective cohort study, 50 HIV-infected renal allograft recipients (27 receiving a PI regimen, 23 receiving a non-PI regimen) transplanted between 2003-2015 were analyzed. RESULTS: Cumulative rejection rates at 12 and 36 months were 41% and 54% in the PI group vs 52% and 86% in the non-PI group. At last follow-up, the overall risk of acute rejection in the PI group was 46% lower compared with the non-PI cohort (P = 0.12). Patients who received a PI-based regimen had significantly reduced graft failure rates (P = 0.027). There was no difference between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies, despite longer follow-up time in the PI group. CONCLUSIONS: Our study suggests that PI-based antiretroviral therapy regimens are associated with improved graft survival and that patients can achieve adequate outcomes on a PI-based regimen when necessary. Due to study limitations, further studies are needed to determine the optimal immunosuppression/antiretroviral therapy regimen post-transplant.

Healthcare-Associated Infections in Cardiac Surgery Patients With Prolonged Intensive Care Unit Stay.

BACKGROUND: Healthcare-associated infections (HAIs) are responsible for many deaths of hospitalized patients each year. Patients with prolonged hospitalization are at high risk for HAIs. Increased efforts have been made to decrease these infections, but a recent report from the Centers for Disease Control suggests that some HAIs may be increasing. We hypothesized that HAIs would remain frequent among cardiac surgery patients with prolonged intensive care unit stay and would be associated with increased mortality. METHODS: We performed a retrospective cohort study of adult cardiac surgery patients with prolonged intensive care unit stay (more than 7 days) over a 3-year period. Mortality differences were calculated based on whether particular HAIs occurred. Multivariable logistic regression was used to examine risk factors associated with the development of HAI. The relationship between HAI and mortality was estimated using propensity score adjusted logistic regression analysis. RESULTS: Of 2,595 patients, 388 (15.0%) had a prolonged intensive care unit stay. Of these patients, 48.5% had at least one HAI. Unadjusted inhospital mortality for patients with HAI was 28.7%, versus 13.0% for patients without. Red blood cell transfusion was associated with increased HAI risk. After propensity score adjustment, surgical site infection and central line associated blood stream infection were associated with increased mortality. The HAIs caused by vancomycin-resistant Enterococcus sp, methicillin-resistant Stapholococcus aureus, and multidrug-resistant organisms appeared to be associated with disproportionally high mortality. CONCLUSIONS: Healthcare-associated infections remain frequent among cardiac surgery patients with prolonged intensive care unit stay and are associated with increased mortality. Evidence-based strategies are needed to reduce these infections.

Diarrhea, bacteremia and multiorgan dysfunction due to an extraintestinal pathogenic Escherichia coli strain with enteropathogenic E. coli genes.

A 55-year-old man with well-controlled HIV had severe diarrhea for 3 weeks and developed multiorgan dysfunction and bacteremia due to Escherichia coli. The genome of the patient's isolate had features characteristic of extraintestinal pathogenic E. coli and genes distantly related to those defining enteropathogenic E. coli.

Anal Cancer Screening in an Urban HIV Clinic: Provider Perceptions and Practice.

In this article, we sought to understand the perceptions and practice of providers on anal cancer screening in HIV-infected patients. Providers in an academic outpatient HIV practice were surveyed. Data were analyzed to determine the acceptability and perceptions of providers on anal Papanicolaou tests. Survey response rate was 55.3% (60.7% among male and 47.4% among female providers). One-third of the providers had received screening requests from patients. Female providers had higher self-rated comfort with anal Papanicolaou tests, with a mean score of 7.1 (95% confidence interval [CI] 4.7-9.5) compared to 3.6 (95% CI 1.5-5.7) for male providers, P = .02. Sixty-seven percent of male providers and 37.5% of female providers would like to refer their patients for screening rather than perform the test themselves. Only 54.2% of our providers have ever performed anal cytology examination. Our survey revealed that not all providers were comfortable performing anal cancer screening for their patients.

Implementation of HIV Palliative Care: Interprofessional Education to Improve Patient Outcomes in Resource-Constrained Settings, 2004-2012.

Palliative care (PC), introduced early in the management of chronic illness, improves patient outcomes. Early integration of a palliative approach for persons with HIV has been documented to be effective in identifying and managing patient-level concerns over the past decade in African settings. The experience of implementing PC in multiple African and other resource-constrained settings (RCSs) emphasizes the need for essential palliative competencies that can be integrated with chronic disease management for patients and their families facing life-limiting illness. This article is an historical description of how basic palliative competencies were observed to be acceptable for health workers providing outpatient HIV care and treatment during eight years of U.S. implementation of "care and support," a term coined to represent PC for persons living with HIV in RCS. The need for team building and interprofessional education is highlighted. The model is currently being tested in one U.S. city and may represent a mechanism for expanding the palliative approach into management of chronic disease. Such competencies may play a role in the development of the patient-centered medical home, a critical component of U.S. health care reform.

Pain Management for Persons Living With HIV Disease: Experience With Interprofessional Education in Nigeria.

CONTEXT: Pain management (PM) has not been routinely incorporated into HIV/AIDS care and treatment in resource-constrained settings. OBJECTIVES: We describe training for multidisciplinary teams tasked with integrating care management into HIV clinics to address pain for persons living with HIV in Nigeria. METHODS: Education on PM was provided to mixed-disciplinary teams including didactic and iterative sessions following home and hospital visits. Participants identified challenges and performed group problem solving. RESULTS: HIV trainers identified barriers to introducing PM reflecting views of the patient, providers, culture, and the health environment. Implementation strategies included (1) building upon existing relationships; (2) preliminary advocacy; (3) attention to staff needs; and (4) structured data review. CONCLUSION: Implementing PM in Nigerian HIV clinics requires recognition of cultural beliefs.