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.

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.

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.

Calcified granulomatous disease: occupational associations and lack of familial aggregation.

PURPOSE: The acute host response to histoplasma capsulatum infection varies according to exposure and susceptibility. Late sequelae include calcifications in the lung, thoracic lymphatics, and spleen. Determinants of calcified granuloma formation are poorly studied and may differ from those affecting acute response. We examined the occupational associations and familial aggregation of radiographic calcified granulomatous disease to characterize the determinants of calcified granuloma formation. METHODS: We analyzed prospectively collected cross-sectional data including computed tomograms from 872 adult members of the Old Order Amish of Lancaster County. RESULTS: Granulomas were present in 71 % of participants. Granulomas were present in the lung of 57 % of participants, in the hilar or mediastinal lymph nodes of 55 % of participants, and in the spleen of 29 % of participants. No significant differences were observed in the presence of granulomas between men and women. Each year of age was associated with 4 % higher odds of splenic calcifications, and a primary occupation of farming was associated with an 84 % higher odds of splenic calcifications. A compelling pattern of familial aggregation was not observed. CONCLUSIONS: Calcified granulomatous disease does not appear to aggregate in families. Determinants influencing patterns of granulomatous disease include occupation, age, and geographic location.

Influenza B-induced refractory cardiogenic shock: a case report.

BACKGROUND: An association between influenza A viruses and myocarditis was noted during the 1918 influenza pandemic. Since then, the link between the influenza B virus and fulminant myocarditis or cardiogenic shock has been rarely reported. CASE PRESENTATION: In February 2013, a 50 year-old-woman without known heart disease presented in profound cardiogenic shock with a left ventricular ejection fraction of 10%. Her presentation was preceded by six days of fever, chills, myalgia and fatigue. She had a junctional tachycardia, a troponin I of 12.6 ng/ml and her coronary angiography demonstrated normal coronary arteries. Percutaneous extracorporeal membrane oxygenation was required. An endotracheal aspirate at admission was positive for influenza B. All other respiratory, blood and urine cultures were negative. On day 7, a repeat echocardiography demonstrated significant recovery of left ventricular function with an ejection fraction of 50%. She was later discharged home in good condition. CONCLUSIONS: Influenza B infection can be complicated by fulminant cardiomyopathy leading to cardiogenic shock in adults without preexisting cardiac disease.

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.

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.

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.

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.

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.

Indicators of adherence to antiretroviral therapy treatment among HIV/AIDS patients in 5 African countries.

As the HIV epidemic threatens the social fabric of countries struggling with HIV prevalence rates as high as 10% to 30%, access to antiretroviral therapy (ART) alone is only the beginning of the clinical challenge. There is a need to identify adherence indicators that will ensure long-term treatment success. A cross-sectional review of 921 adult patients on ART for at least 1 year was conducted. Through an administered adherence survey, key indicators were found to be highly correlated with patient adherence. The adherence rate in this sample was 72% after being on treatment for an average of 15 months. This data suggest that having a high perceived quality of care and owning one's own home positively affected patients' adherence. Indicators such as alcohol use in the last month and a high level of depression negatively affected patients' adherence. Targeting specific indicators for specific interventions will guard against nonadherence, leading to treatment failure.

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.

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.

Viral load decay in antiretroviral-naïve patients receiving once-daily tenofovir and emtricitabine plus twice-daily nevirapine.

PURPOSE: The once-daily nucleoside reverse transcriptase inhibitor backbone of tenofovir and emtricitabine has been proven effective in combination with efavirenz and protease inhibitors in large clinical trials. This study evaluated tenofovir and emtricitabine in combination with nevirapine. METHODS: Viral load was assessed at baseline, Day 3, and Day 7 in addition to Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84 in 10 antiretroviral-naïve patients participating in an open-label clinical trial of tenofovir and emtricitabine once daily in combination with nevirapine twice daily. RESULTS: All patients achieved viral decay with this combination. Two patients discontinued prior to virologic suppression, one with a viral load of 55 copies/mL. Virologic suppression (<50 copies/mL) was achieved by Week 24 in the remaining 8 patients. An undetectable viral load was maintained during > or =60 weeks follow-up. CONCLUSION: In this study of treatment-naïve patients, the combination of tenofovir and emtricitabine plus twice-daily nevirapine produced sustained viral load decay in patients including those with a high baseline viral load.

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.

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.

Tenofovir and abacavir combination therapy: lessons learned from an urban clinic population.

Regimens containing abacavir (ABC), tenofovir (TDF), and lamivudine (3TC) have recently been demonstrated to have high failure rates. This poses a clinical dilemma of how to manage patients currently being treated with other regimens containing tenofovir/abacavir. We evaluated the outcomes of tenofovir/abacavir regimens in our clinical practice through a retrospective review of 2655 charts. Two hundred patients (7%) were on a tenofovir/abacavir-containing regimen. Fifty-nine patients met the criteria for analysis and were grouped into three groups: (1) antiretroviral naïve, (2) virally suppressed patients switched to TDF/ABC, and (3) patients with failure of their first antiretroviral regimen. Rates of viral suppression in the naïve, switch, and first-failure groups were 95%, 86%, and 46%, respectively. In the first-failure group, viral suppression was 66% without and 18% with a preexisting M184V. A composite analysis of the groups revealed a success rate of 86% when the regimen contained zidovudine (ZDV) and 62% when it did not. No K65R mutations were noted. These findings support continued caution in the use of TDF/ABC in combination. However, these data suggest that this combination may be successfully used in selected situations such as in combination with ZDV. In patients already virally suppressed on a TDF/ABC-containing regimen, considerations include continuing the regimen or adding zidovudine, in the attempt to protect against the development of a K65R mutation and/or virologic failure, versus changing a stable regimen.