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Background Texas has one of the highest rates of uninsured populations in the US (Fig1). We hypothesized that those without insurance were more likely to be hospitalized for COVID-19 but were at higher risk for severe disease and mortality due to uncontrolled medical illness prior to hospitalization. Methods We conducted a retrospective analysis of patients hospitalized in 81 hospitals in Dallas- Ft. Worth (DFW) area. All inpatients and outpatients with COVID-19 from 3/1/2020 to 4/1/2021 were included to examine risk for hospitalization. Subset analysis included those hospitalized with COVID-19. Data presented is comparison between Medicaid and uninsured population as they were similar in age distribution (Fig 2). Results 198, 174 COVID-19 unique individuals were identified; 7.5% had Medicaid and 25.1% were uninsured. Among Medicaid, 29.6% were hospitalized vs. 25.8% of Medicaid vs. uninsured (adjusted odds ratio (aOR) 1.26 (1.20, 1.33). Among the 71,778 (∼36%) hospitalized for COVID-19, comparing Medicaid vs. uninsured: 44.9 vs. 56.3% had ICU care; 51.4% vs. 80.2% had pneumonia, 41.1% vs. 67.5% had respiratory failure with higher odds of developing these outcomes in uninsured (see Table 1). Median duration of hospital stay was longer in uninsured than Medicaid ( see Table 2a) and mortality in the hospital was 7.4% vs. 7.9% among Medicaid vs. uninsured (p< 0.0001). Thirty-day readmission rates were lower for Medicaid vs. uninsured (Table 3). In the year prior to the COVID-19 hospitalizations, use of health care among the uninsured was lower compared to Medicaid patients for outpatient, inpatient, and ER visits (p< 0.0001 for all comparisons; see Table 2b). Conclusion Uninsured in North Texas had lower odds of hospitalization vs. Medicaid patients, likely due to younger age, but once hospitalized had higher risk for COVID pneumonia, ICU care, and respiratory failure. Median number of days was higher among uninsured but in-hospital mortality was higher among Medicaid population. Prior contact with healthcare system was lower among uninsured and 30-day readmissions were also lower, suggesting barriers accessing health care. Poorer outcomes among uninsured once hospitalized may be due to untreated co-morbidities (Fig 3). Expansion of Medicaid has the potential of ameliorating these disparities. Figure 3Conclusion graphic Disclosures Mamta K. Jain, MD, MPH, Gilead Sciences: Grant/Research Support|GSK/ViiV: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Regeneron: Grant/Research Support Mae Thamer, PhD, Gilead: Grant/Research Support Kavita Bhavan, MD, MPH, Gilead: Grant/Research Support.

Background Lack of childcare has been linked to missed healthcare appointments, especially among lower-income women. The COVID-19 pandemic created additional stressors for many low-income families that already struggled to meet childcare and healthcare needs, impacting women’s health and daily life experiences in unknown ways. By exploring the experiences of women who were referred for childcare services at a US safety-net health system, we aimed to understand the challenges women faced in managing their health and childcare needs during the COVID-19 pandemic. Methods We conducted semi-structured interviews with participants in Dallas County, TX between August 2021 and February 2022. All participants were referred from the county’s safety-net hospital system’s women’s health clinics to an on-site drop-off childcare center by staff who identified lack of childcare as a barrier to accessing healthcare. Participants were the primary caregiver for at least 1 child ≤ 13 years. Interviews were conducted in English or Spanish. We analyzed data using thematic content analysis. Results We interviewed 22 female participants (mean age 34 years); participants had on average 3 children and primarily identified as Hispanic or African American. Three interrelated themes emerged from the data: disruptions in access to healthcare, the inextricable link between childcare and health, and emotional distress. Conclusions Our findings emphasize the intersectionality of family and social context with a patient’s health and add to our understanding of childcare as a social need.

Aim To compare the efficacy of Negative Pressure Wound Therapy (NPWT) with and without irrigation with 0.1% polyhexanide-betaine. Methods We randomized 150 subjects in a 16-week RCT to compare healing in patients with diabetic foot infections. NPWT delivered at 125 mm Hg continuous pressure. NPWT-I were administered at 30 cc per hour. Results There were no differences clinical treatment or outcomes: wound area after surgery (18.5 ± 19.0 vs. 13.4 ± 11.1 cm2, p = 0.50), duration of antibiotics (39.7 ± 21.0 vs. 38.0 ± 24.6 days, p = 0.40), number of surgeries (2.3 ± 0.67 vs. 2.2 ± 0.59, p = 0.85), duration of NPWT (148.1 ± 170.4 vs. 114.5 ± 135.1 h, p = 0.06), healed wounds (58.7% vs. 60.0%, p = 0.86), time to healing (56.3 ± 31.7 vs. 50.7 ± 27.8, p = 0.53), length of stay (13.8 ± 6.4 vs. 14.5 ± 11.2 days, p = 0.42), re-infection (20.0% vs. 22.7%, p = 0.69, and re-hospitalization (17.3% vs. 18.7, p = 0.83). Conclusions The addition of irrigation to NPWT did not change clinical outcomes in patients with diabetic foot infections. Clinical trial number NCT02463487, ClinicalTrials.gov .

The aim of this study was to report clinical outcomes of moderate and severe foot infections in patients without diabetes. Medical records of 88 nondiabetic patients with foot infections treated at a safety net hospital were retrospectively reviewed. Patients were grouped by the presence of soft-tissue infection (STI) or osteomyelitis (OM). The diagnosis of OM was determined by positive bone culture or histopathology. STIs were defined by negative bone biopsy or negative imaging with magnetic resonance imaging or computed tomography/dual-modality radiolabeled white blood cell single-photon emission computed tomography. Patient outcomes were recorded ≤1 year after admission. Eighty-eight nondiabetic patients admitted to our institution for moderate or severe foot infections were included, 45 OM and 43 STI. No differences were noted in patient characteristics except that OM patients had a higher prevalence of neuropathy (66.7% versus 39.5%, p = .02). OM patients required surgery more often (97.8% versus 67.4%, p.01), a greater number of surgeries (2.0 ± 1.2 versus 1.4 ± 1.3, p = .02), and more amputations (75.6% versus 11.6%, p.01) than STI patients. OM patients had a higher proportion of wounds that healed (82.2% versus 62.8%, p = .04). There were no significant differences in reinfection (35.6% versus 25.6%, p = .36), foot-related readmission to hospital (35.6% versus 23.3%, p = .25), or total duration of antibiotics (13.9 ± 10.2 versus 13.5 ± 12.9, p = .87) between OM and STI patients. In conclusion, OM patients required more surgeries and amputations than patients with STIs; however, they had similar rates of reinfection and readmission within a year after the index hospitalization.

Background Distinguishing osteomyelitis from soft-tissue infection of the foot is important because osteomyelitis is associated with more operations, amputation, and prolonged antibiotic exposure. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely ordered inflammatory biomarkers for evaluating foot infection. When initial evaluation is inconclusive, advanced imaging is indicated, and high clinical or radiographic suspicion of osteomyelitis may indicate bone biopsy to identify organisms and antibiotic sensitivity. Although ESR and CRP levels are helpful for distinguishing osteomyelitis from soft-tissue infections in patients with diabetes-related foot infections, parameters regarding optimal cutoff values for those tests have not, to our knowledge, been defined. Questions/purposes (1) What are the optimal cutoff values for ESR and CRP to differentiate osteomyelitis from soft-tissue infection in patients with diabetes-related foot infection? (2) Can a diagnostic algorithm be derived to guide interpretation of ESR and CRP to improve recognition of osteomyelitis in the setting of diabetic foot infection? Methods The medical records of 1842 patients between 18 and 89 years of age treated at our institution between January 1, 2010 and February 6, 2017 for foot infection were reviewed. For inclusion, patients must have had a diagnosis of diabetes mellitus, moderate or severe infection, ESR and CRP values within 72 hours of admission, either advanced imaging (MRI or single-positron emission computed tomography/computed tomography [SPECT/CT]) or bone biopsy during admission and must not have had comorbidities that could affect ESR and CRP, such as autoimmune disorders. As such, 1489 patients were excluded, and 353 patients were included in the study. Osteomyelitis was diagnosed by positive bone culture or histopathology. Osteomyelitis was considered to be absent if there was a negative MRI or SPECT/CT result, or negative bone culture and histology findings if imaging was inconclusive. We identified 176 patients with osteomyelitis and 177 with soft-tissue infection. A blinded investigator performed the statistics. Optimal cutoffs of ESR and CRP were determined using receiver operative characteristic (ROC) analysis. A diagnostic algorithm was determined using epidemiologic principles of screening evaluations. Results An ESR of 60 mm/h and a CRP level of 7.9 mg/dL were determined to be the optimal cutoff points for predicting osteomyelitis based on results of the ROC analysis. The ESR threshold of 60 mm/h demonstrated a sensitivity of 74% (95% confidence interval [CI], 67-80) and specificity of 56% (95% CI, 48-63) for osteomyelitis, whereas the CRP threshold of 7.9 mg/dL had a sensitivity of 49% (95% CI, 41-57) and specificity of 80% (95% CI, 74-86). If the ESR is 60 mm/h and CRP level is > 7.9 mg/dL, the likelihood of osteomyelitis is high, and treatment of suspected osteomyelitis should be strongly considered. Conclusions While ESR is better for ruling out osteomyelitis initially, CRP helps distinguish osteomyelitis from soft-tissue infection in patients with high ESR values. Further prospective studies addressing the prognostic value of ESR and CRP are needed, and a more comprehensive diagnostic algorithm should be developed to include other diagnostic tests such as probe-to-bone and imaging. Level of evidence Level III, diagnostic study.

Background Nearly 20% of people in the United States use drugs each year. People who use drugs (PWUD) are predisposed to complex infections that require long term intravenous (IV) antibiotics. A frequent clinical quandary in PWUD is safe administration of extended IV antibiotics. Current standard of care is IV antibiotic administration in skilled nursing facilities. In this system, PWUD frequently do not finish antibiotic therapy, resulting in avoidable complications of untreated infections and increased healthcare utilization. We present a pilot study of ten patients with a history of addiction who required long-term IV antibiotics to evaluate the feasibility of self administered outpatient parenteral antibiotic therapy (S-OPAT) for PWUD. Methods Ten patients who had a history of mild addiction and stable housing, social support and transportation were enrolled at Parkland Health and Hospital System to complete S-OPAT. We extracted demographic, drug use, clinical and access to care variables and patients were followed with weekly clinical appointments. Addiction severity was defined using the National Institute of Drug Abuse (NIDA) -Modified ASSIST Score. We completed post-intervention surveys to evaluate the impact of the intervention on provider-patient trust. Results A total of 10 patients were enrolled in S-OPAT (Table 1). The patients were 48 years old on average, all were male and seven were Hispanic. All patients had stimulant use disorder and no patients had commercial insurance. Treated infections were bone/ joint and skin/soft tissue in origin. All patients completed their antibiotic course, nearly all appointments were attended (96%) and there were no 30-day hospital readmissions (Table 2). More than two-third of patients experienced improvement in addiction severity with progress in multiple psychosocial factors including housing instability, social support and legal problems (Figure 1; Table 2). Table 1. Demographic, substance use and clinical variables among people who use drugs enrolled in the pilot project for S-OPAT (N=10). Table 2. Clinical, drug use and psychosocial outcomes among people who use drugs and received S-OPAT (N=10). Addiction severity was defined using the National Institute of Drug Abuse (NIDA) -Modified ASSIST Score. Figure 1. Progression of addiction severity before and after completion of self-administered outpatient parenteral antibiotic therapy pilot among patients with a history of drug use (N=10). Addiction severity was defined using the National Institute of Drug Abuse (NIDA) -Modified ASSIST Score. Conclusion We demonstrate that PWUD can successfully complete S-OPAT with simultaneous improvement in addiction severity and psychosocial factors. We hope to create a framework for the patient-centered administration of extended courses of antibiotics for PWUD and to advocate for the expansion of individualized approaches to extended courses of IV antibiotics for PWUD. Disclosures All Authors: No reported disclosures

Purpose: Influenza/pneumonia is the eighth leading cause of death in the United States. The 2020-2021 influenza season is predicted to be further impacted by COVID-19 infections. Historical data reflect disproportionate morbidity and mortality rates in the Hispanic population for influenza and COVID-19. Influenza vaccination rates remain low in the Hispanic community. We aim to improve vaccination through a community-led event, partnering with the Cristo Rey School Dallas, located in a zip code with a higher age-adjusted influenza/pneumonia mortality rate. A survey was administered to adults attending the Influenza vaccine event to understand attitudes and perceptions about influenza, vaccination, and effective messaging strategies for the campaign. Methods: Messaging was cocreated with student health ambassadors to promote immunization and delivered through trusted sources. The health department administered vaccines to individuals >age 3 at no cost. Adults were asked to complete a 19-question survey postvaccination offered in both English and Spanish. Results: Two hundred and forty-one of 394 (61.2%) participants completed the survey. Ninety-eight percent identified as Hispanic/Latino, and the majority of surveys were administered in Spanish. Among Spanish language participants, the church bulletins (57.3%) and Spanish language radio (30.5%) were reported to be most effective modes of messaging versus word of mouth (32.9%) and social media (26.3%) for English-speaking participants. Sixteen percent of participants surveyed had never received an influenza vaccine before this event. Conclusion: Cocreated messaging delivered by trusted sources in the Hispanic community led to a successful Influenza vaccine drive with the Dallas County health department.

Background We aimed to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections (DFIs). Methods Thirty-five patients with DFIs were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histologic analysis initially and for recurrence. Fisher exact and χ2 tests were used for dichotomous variables and Student t and Mann-Whitney U tests for continuous variables (α = .05). Results Twenty-four patients were diagnosed as having osteomyelitis and 11 as having soft-tissue infections. Four patients (16.7%) with osteomyelitis had reinfection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), reulceration (20.8%), readmission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed as having osteomyelitis versus soft-tissue infections. There were no differences in osteomyelitis reinfection (16.7% versus 45.5%; P = .07), wounds that failed to heal (8.3% versus 9.1%; P = .94), reulceration (20.8% versus 27.3%; P = .67), readmission for DFIs at the same site (16.7% versus 36.4%; P = .20), amputation at the same site after discharge (12.5% versus 36.4%; P = .10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate of 8.3% to 20.8%. Conclusions Most osteomyelitis markers were similar to markers in soft-tissue infection. Commonly reported surrogate markers were not shown to be specific to identify patients who failed osteomyelitis treatment compared with patients with soft-tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.

Background: Palliative use of continuous IV inotrope therapy has shown to improve quality of life and reduce hospital readmissions for patients with end-stage heart failure (HF) who are otherwise ineligible to receive advanced therapies. Administration of home inotrope therapy generally requires a hospice or home-health agency, placing this option out of reach for patients who lack funding. As such, underinsured patients are relegated to the difficult choice of either remaining in the hospital to receive IV inotropes, or going home without the therapy for as long as their symptoms allow. To address this issue at our large county safety-net hospital, we developed and implemented a patient self-administered home inotrope therapy program. Methods: A multidisciplinary team of physicians, pharmacists, nurses, and social workers was assembled to pilot the program. Eligible patients were provided with a peripherally inserted central venous catheter (PICC) and a portable infusion pump. They were then instructed on proper use of the pump, medication administration, medication bag changes, and IV line care using a nursing teach-back technique. After proper understanding was demonstrated, patients were discharged home with weekly follow up in heart failure clinic for PICC-care and medication exchanges. Results: During the initial 12 months of the program, 5 patients were deemed eligible for enrollment. Total hospitalized days for these patients was 277 (mean = 55.4 days) in the one year prior to enrollment and 12 (mean = 2.4 days) while enrolled for a cumulative period of 288 days (Figure 1). One patient was able to secure funding for advanced therapies, two patients died while enrolled, and two patients are currently enrolled and alive. Discussion: A self-administered home IV inotrope therapy program is a feasible alternative for palliation in unfunded patients with end-stage HF who are otherwise not candidates for advanced therapies, allowing for more days at home in the end of life. Thus far, the cost impact of the program has been mitigated by the cost savings for inpatient hospitalizations. Studies to assess patient-centered outcomes, and overall cost savings are ongoing.

Magnetic resonance imaging (MRI) is the recommended diagnostic imaging technique for diabetic foot osteomyelitis (DFO). The gold standard to diagnose osteomyelitis is bone biopsy with a positive culture and/or histopathology finding consistent with osteomyelitis. The purpose of this study is to assess the accuracy of MRI readings in biopsy-proven diabetic foot osteomyelitis with a second read done by a blinded, expert musculoskeletal radiologist. A retrospective chart review of 166 patients who received a bone biopsy to confirm the diagnosis of a suspected DFO at a large county hospital between 2010 and 2014. A second, blinded musculoskeletal radiologist reviewed the images for accuracy, once the official reading was recorded. Imaging results were correlated with the final diagnosis of osteomyelitis determined by bone biopsy. In 17 of 58 patients (29.3%), the diagnosis of DFO by MRI was not confirmed by bone biopsy. There were 12 false positives and 5 false negatives. After the second expert read, there were 5 false positives and 4 false negatives. The overall accuracy was 84% for the second read. Our study demonstrated results comparable to the previously reported meta-analysis findings. There is a clear variation on the read of MRI that could lead to an incorrect diagnosis of DFO. An integrated approach with evaluation of clinical findings, communication with radiologist about the MRI results when indicated, and bone biopsy is warranted for accurate diagnosis management of DFO.

In this study, we assessed the effectiveness of inflammatory markers to diagnose and monitor the treatment of osteomyelitis in the diabetic foot. We evaluated 35 consecutive patients admitted to our hospital with infected foot ulcers. Patients were divided in two groups based on the results of bone culture and histopathology: osteomyelitis and no osteomyelitis. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNFα), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP1α) were measured at baseline after 3 and 6 weeks of standard therapy. PCT levels in the osteomyelitis group were significantly higher at baseline than in the group with no osteomyelitis (P = 0·049). There were no significant differences between the two groups in the levels of the other markers. CRP, ESR, PCT and IL-6 levels significantly declined in the group with osteomyelitis after starting therapy, while MCP-1 increased (P = 0·002). TNFα and MIP1α levels were below range in 80 out of 97 samples and therefore not reported. Our results suggest that PCT might be useful to distinguish osteomyelitis in infected foot ulcers. CRP, ESR, PCT and IL-6 are valuable when monitoring the effect of therapy.

BACKGROUND: Distinguishing osteomyelitis from soft-tissue infection of the foot is important because osteomyelitis is associated with more operations, amputation, and prolonged antibiotic exposure. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely ordered inflammatory biomarkers for evaluating foot infection. When initial evaluation is inconclusive, advanced imaging is indicated, and high clinical or radiographic suspicion of osteomyelitis may indicate bone biopsy to identify organisms and antibiotic sensitivity. Although ESR and CRP levels are helpful for distinguishing osteomyelitis from soft-tissue infections in patients with diabetes-related foot infections, parameters regarding optimal cutoff values for those tests have not, to our knowledge, been defined. QUESTIONS/PURPOSES: (1) What are the optimal cutoff values for ESR and CRP to differentiate osteomyelitis from soft-tissue infection in patients with diabetes-related foot infection? (2) Can a diagnostic algorithm be derived to guide interpretation of ESR and CRP to improve recognition of osteomyelitis in the setting of diabetic foot infection? METHODS: The medical records of 1842 patients between 18 and 89 years of age treated at our institution between January 1, 2010 and February 6, 2017 for foot infection were reviewed. For inclusion, patients must have had a diagnosis of diabetes mellitus, moderate or severe infection, ESR and CRP values within 72 hours of admission, either advanced imaging (MRI or single-positron emission computed tomography/computed tomography [SPECT/CT]) or bone biopsy during admission and must not have had comorbidities that could affect ESR and CRP, such as autoimmune disorders. As such, 1489 patients were excluded, and 353 patients were included in the study. Osteomyelitis was diagnosed by positive bone culture or histopathology. Osteomyelitis was considered to be absent if there was a negative MRI or SPECT/CT result, or negative bone culture and histology findings if imaging was inconclusive. We identified 176 patients with osteomyelitis and 177 with soft-tissue infection. A blinded investigator performed the statistics. Optimal cutoffs of ESR and CRP were determined using receiver operative characteristic (ROC) analysis. A diagnostic algorithm was determined using epidemiologic principles of screening evaluations. RESULTS: An ESR of 60 mm/h and a CRP level of 7.9 mg/dL were determined to be the optimal cutoff points for predicting osteomyelitis based on results of the ROC analysis. The ESR threshold of 60 mm/h demonstrated a sensitivity of 74% (95% confidence interval [CI], 67–80) and specificity of 56% (95% CI, 48–63) for osteomyelitis, whereas the CRP threshold of 7.9 mg/dL had a sensitivity of 49% (95% CI, 41–57) and specificity of 80% (95% CI, 74–86). If the ESR is < 30 mm/h, the likelihood of osteomyelitis is low. However, if ESR is > 60 mm/h and CRP level is > 7.9 mg/dL, the likelihood of osteomyelitis is high, and treatment of suspected osteomyelitis should be strongly considered. CONCLUSIONS: While ESR is better for ruling out osteomyelitis initially, CRP helps distinguish osteomyelitis from soft-tissue infection in patients with high ESR values. Further prospective studies addressing the prognostic value of ESR and CRP are needed, and a more comprehensive diagnostic algorithm should be developed to include other diagnostic tests such as probe-to-bone and imaging. LEVEL OF EVIDENCE: Level III, diagnostic study.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with significant healthcare costs, morbidity, and mortality in the United States. Complications of MRSA bacteremia include infective endocarditis, osteomyelitis, and sepsis, all of which are difficult to treat. Time to effective therapy and antibacterial choice greatly affect patient outcomes. Vancomycin and daptomycin remain first-line therapies; however, reports of vancomycin-associated treatment failure and reduced daptomycin susceptibility highlight the need to define alternative strategies for MRSA bacteremia treatment. In addition, several patient- and pathogen-specific factors influence the outcomes of MRSA bacteremia. It is, therefore, critical to explore the interaction between host- and pathogen-specific factors and its effect on MRSA bacteremia pathogenesis and mortality. This review discusses the factors that drive the development of MRSA bacteremia and examines alternative treatment strategies.

Background: Anti-staphylococcal penicillins have long been the first-line treatment option for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Recent retrospective data comparing nafcillin and cefazolin report similar clinical efficacy despite concerns about high inoculum MSSA infections. Methods: This was a retrospective, non-inferiority, cohort study comparing treatment failure rates between nafcillin and cefazolin in patients with MSSA bacteremia from any source, other than meningitis. Multiple logistic regression was used to adjust for confounding variables. Results: A total of 142 patients were included in the study. The overall treatment failure rate among patients receiving cefazolin was non-inferior to nafcillin (11.3% versus 8.5%; 90% confidence interval −5.2% to 10.8%). Rates of adverse drug events were significantly higher in the nafcillin arm (19.7% versus 7%; p = 0.046). After adjustment for confounding variables, no difference between treatment groups was found in treatment failure (adjusted odds ratio (OR) = 1.2; 95% CI, 0.3–4.5), but nafcillin was associated with significantly higher nephrotoxicity (adjusted odds ratio (OR) = 5.4; 95% CI, 1.1–26.8). Conclusion: Cefazolin was associated with lower nephrotoxicity and similar treatment failure rates compared to nafcillin suggesting that cefazolin is an appealing first line agent for most MSSA bloodstream infections. Keywords: Nafcillin, Cefazolin, Methicillin-susceptible Staphylococcus aureus, MSSA, Bacteremia

Diabetic foot complications are common, costly, and difficult to treat. Peripheral neuropathy, repetitive trauma, and peripheral vascular disease are common reasons that lead to ulcers, infection, and hospitalization. Individuals with diabetes presenting with foot infection require optimal medical and surgical management to accomplish limb salvage and prevent amputation; aggressive short-term and meticulous long-term care plans are required. Multiple classification systems have been recommended to ease the understanding and the management of these infections. Multi-disciplinary approach is the mainstay for a successful management. Such teams typically include multiple medical, surgical, and nursing specialties across a variety of public and private health care systems. This article is an overview in how to medically and surgically approach the diabetic foot infection with emphasis in soft tissue infection.

Objective : The purpose of this study was to evaluate risk factors for methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized for diabetic foot infections. Methods : We reviewed hospital admissions for foot infections in patients with diabetes which had nasal swabs, and anaerobic and aerobic tissue cultures at the time of admission. Data collected included patient characteristics and medical history to determine risk factors for developing an MRSA infection in the foot. Results : The prevalence of MRSA in these infections was 29.8%. Risk factors for MRSA diabetic foot infections were history of MRSA foot infection, MRSA nasal colonization, and multidrug-resistant organisms (p

This study was designed to compare two approaches to negative-pressure wound therapy: 125-mmHg pressure with a polyurethane foam dressing and 75-mmHg pressure with a silicone-coated dressing.Forty patients with diabetic foot wounds, after incision and drainage or amputation for infection, were assigned randomly to negative-pressure wound therapy with 75-mmHg continuous pressure with a silicone-covered dressing (75-mmHg group) or 125-mmHg with a polyurethane foam dressing (125-mmHg group) for up to 4 weeks or until surgical closure.There was no difference in the proportion of wounds that were closed surgically (75-mmHg group, 50 percent; 125-mmHg group, 60 percent), wounds that demonstrated 50 percent wound area reduction (75-mmHg group, 65 percent; 125-mmHg group, 80 percent), or wounds that demonstrated 50 percent wound volume reduction after 4 weeks of therapy (75-mmHg group, 95 percent; 125-mmHg group, 90 percent).The authors' results suggest that there was no difference in outcomes in wounds treated with low pressure (75 mmHg) with a silicone-coated interface and high pressure (125 mmHg) with a polyurethane foam interface.Therapeutic, II.

Background Self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT) is offered at Parkland Memorial Hospital for uninsured patients requiring an extended course of intravenous (IV) antibiotics to complete treatment at home.1 At Parkland, S-OPAT has been demonstrated to be safe and effective with >70,000 inpatient bed days avoided to date, lower 30-day readmission rates, and significant cost savings.1 Patients with a history of substance use are not eligible for S-OPAT and are discharged to skilled nursing facilities (SNF) to complete IV antibiotic therapy. This study aims to describe clinical outcomes of a patient population with history of substance use discharged to SNF for OPAT. Methods The electronic medical record was used to identify patients with substance use discharged to an SNF for OPAT between January 1, 2017 and April 30, 2018. Data were retrospectively reviewed for demographics, substance use history, treatment plan and clinical outcomes. Results 76 patients with history of substance use were discharged to SNFs for OPAT in the study period. 62% of patients reported non-IV drug use and 38% reported IV drug use (IVDU). The mean age for patients with non-IV drug use was 47 (83% male) vs. 43 years for patients with IVDU (86% male). Of patients with non-IV drug use, 30% reported cocaine use, 11% methamphetamine use and 59% polysubstance use or other. Of patients with IVDU, 38% reported heroin use, 10% methamphetamine use and 52% polysubstance use or other. When comparing outcomes of IVDU vs. non-IV drug use patients, 34% vs. 21% did not complete the prescribed treatment course, 28% vs. 11% left against medical advice (AMA), and 20% vs. 15% were readmitted to the hospital within 30 days. Conclusion The majority of patients with substance use, 74%, completed their prescribed IV antibiotic course when sent to an SNF. However, a subset of these patients is at risk for poor clinical outcomes. A greater proportion of patients with prior IVDU compared with patients with prior non-IV drug use left treatment AMA and were readmitted to our hospital within 30 days of discharge. Future efforts to identify patients with substance use disorder who may be appropriate for S-OPAT with integration of addiction medicine services may improve clinical outcomes. Disclosures Ank E. Nijhawan, MD, MPH, Gilead Sciences, Inc.: Research Grant.

This study sought to assess the utility of monitoring response to treatment of diabetic foot osteomyelitis (DFO) with Tc-99m WBC-labelled single photon emission computed tomography (SPECT/CT) imaging. This is a retrospective cohort study of 20 patients with DFO with sequential Tc-99m WBC-labelled SPECT/CT imaging. Radiologic findings of osteomyelitis were evaluated and imaging results were correlated with clinical outcomes subtracted from chart review. Successful treatment of osteomyelitis was defined by wound healing and/or lack of re-admission for bone infection of the same site within 1 year. The sensitivity, specificity, positive predictive value and negative predictive value of SPECT/CT to determine osteomyelitis treatment remission were 90%, 56%, 69% and 83%, respectively. Tc-99m WBC-labelled SPECT/CT imaging may be useful to help determine treatment outcomes for DFO.

Magnetic resonance imaging (MRI) is the recommended diagnostic imaging technique for diabetic foot osteomyelitis (DFO), with a reported accuracy of 79%. The gold standard to diagnose osteomyelitis is bone biopsy, with a positive culture and/or histopathology findings consistent with osteomyelitis. The purposes of this study are to assess the accuracy of technetium-99m (Tc-99m) labeled white blood cell (WBC) single-photon emission computed tomography/computed tomography (SPECT/CT) hybrid imaging for diagnosing DFO confirmed by bone biopsy and to compare that to the diagnostic accuracy of an MRI.The authors performed a retrospective chart review of 166 patients who received a bone biopsy to confirm the diagnosis of a suspected DFO at a large municipal hospital between 2010 and 2013. Patients were selected on the basis of whether they received an MRI or a SPECT/CT. Patients whose scans were not within a clinically relevant time frame of the biopsy were excluded. Imaging results were correlated with probability of osteomyelitis determined by bone biopsy.For inclusion criteria, 110 patients met the study's criteria: 52 SPECT/CT patients and 58 MRI patients. The sensitivity, specificity, positive predictive value, and negative predictive value of SPECT/CT were 89%, 35%, 74%, and 60%, respectively; the corresponding values for MRI were 87%, 37%, 74%, and 58%, respectively. There were no significant differences in accuracy of diagnosing DFO between imaging techniques.This data suggests that the diagnostic accuracy of SPECT/CT imaging in DFOs is similar to an MRI.

Background In the wake of Hurricane Maria, hospitals nationwide have faced a shortage of IV fluids sourced from Puerto Rico. Out of necessity to conserve IV fluids, Parkland Memorial Hospital shifted IV antibiotic administration from traditional fluid suspension via pump/gravity to “IV push” administration. The safety and potential cost savings of short infusion administration of antibiotics have been previously described; however, implementation of IV push administration among patients receiving long-term IV antibiotics has yet to be described. Methods Starting November 2017, patients requiring long-term IV antimicrobial treatment with were transitioned to receive IV push administration from infusion. Per the Parkland self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT), patients were screened and trained to self-administer IV antibiotics prior to hospital discharge and followed in the Parkland OPAT clinic. Results Since implementation November 2017, 200 patients completed antimicrobial therapy with IV push method with 100% success rate and no reported complications. The following supplies were estimated to be saved: 3,000 less IV fluid bags, 1,000 IV tubing, and 50% fewer gloves and alcohol swabs, amounting to approximately $22,000 of cost savings for a patient going home on once a day antibiotic therapy. Teaching time for the nursing team was reduced on average by 50% per patient. Preliminary patient satisfaction surveys indicate greater satisfaction due to decreased infusion time from an average of 45 minutes to 3–5 minutes with the IV push method. Patient’s reported satisfaction with the new IV Push method due to greater convenience for both storing the medication and a faster preparation time. Conclusion Parkland Memorial Hospital was able to implement IV push as a safe and cost-effective alternative to traditional IV antibiotic administration in fluid suspension. Use of IV push antibiotics resulted in $22,000 of cost savings and reduced utilization of a critical resource currently facing a nationwide shortage. Though implemented at our institution in response to a national crisis, IV push is a favorable alternative to administration via a pump or gravity due to time savings, cost reduction, and convenience. Disclosures All authors: No reported disclosures.

Background Methicillin-susceptible Staphylococcus aureus (MSSA) infections are traditionally treated with intravenous (IV) nafcillin, oxacillin, or cefazolin, all antibiotics that require multiple doses per day. Despite theoretical limitations of using ceftriaxone in MSSA infections, some clinical studies suggest noninferiority of ceftriaxone compared with standard of care. At Parkland Memorial Hospital, many patients diagnosed with MSSA infections receive self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT). Daily-dosed ceftriaxone is often used for convenience and feasibility of medication adherence. Methods We conducted a retrospective cohort study among S-OPAT patients receiving cefazolin and ceftriaxone for treatment of MSSA infections. We compared infection type and planned duration of therapy as baseline differences between the treatment cohorts. Our clinical outcomes of interest were 30-day readmission rates and treatment failure as defined by repeat positive blood culture within 6 months. Results We identified 184 patients treated with cefazolin and 74 patients treated with ceftriaxone. Characteristics of treatment plan are shown in Table 1. There were no statistically significant differences in infection type or mean duration of therapy between the two treatment cohorts. Outcomes are shown in Table 2. There were no statistically significant differences in readmission rates and rate of treatment failure. Conclusion Our retrospective review suggests patients treated with ceftriaxone for MSSA bacteremia had similar clinical outcomes as those treated with cefazolin. While this study is limited in its retrospective nature, the findings suggest that ceftriaxone may be a safe and more convenient antibiotic option in certain MSSA infections. Disclosures All authors: No reported disclosures.

Background Self-administered outpatient parenteral antimicrobial therapy (S-OPAT) is a self-care treatment modality in which patients requiring extended courses of intravenous antibiotics are trained to safely self-administer treatment via indwelling catheter in their own homes.1,2 A large proportion of S-OPAT patients are baseline diabetics who present with osteomyelitis and soft-tissue infections associated with poor glycemic control.3 Given the degree of patient activation demanded by the S-OPAT program, we hypothesized that S-OPAT may benefit patients in other self-care modalities, including diabetes self-management. Methods We conducted a before-after retrospective analysis of diabetic patients receiving S-OPAT. Outcomes were compared between the 6-month period prior to and the 6-month period following initiation of S-OPAT. Outcomes of diabetes self-management included HgbA1c, diabetes medication adherence (as measured by proportion of days covered, or PDC), and use of any diabetes medication. A subgroup HgbA1c analysis was conducted among insulin users. Difference in outcome was tested for significance using paired t-tests. Results A total number of 348 diabetic S-OPAT patients were identified. The mean HgbA1c decreased by 1.82 from the 6 months prior to the 6 months after initiation of S-OPAT (P < 0.001). Subgroup analysis showed an additional significant reduction in HgbA1c among insulin users (P = 0.002). There were no differences in adherence rates to diabetes medications or initiation of medications pre and post-initiation of S-OPAT (P > 0.05). Conclusion Initiation of S-OPAT was associated with a significant reduction in HgbA1c among diabetic patients. A similar reduction was noted among insulin users, a group requiring a higher level of self-care. Reduction in HgbA1c was not attributable to changes in medication regimens or adherence. Resolution of infection alone is not sufficient to explain the marked reduction in HgbA1c demonstrated pre- and post-initiation of S-OPAT. We hypothesize that the degree of patient engagement obtained through the S-OPAT model yields collateral benefits in other aspects of self-care, including glycemic control. Disclosures All authors: No reported disclosures.

Since the advent of highly active antiretroviral therapy, life expectancies for persons with HIV infection are similar to those for uninfected people. A growing proportion of HIV-infected individuals are now over the age of 50. We are also seeing an increase in the incidence of HIV infection in older adults. To meet the challenges of the ongoing HIV epidemic, prevention efforts should include a focus on older adults. Also, HIV care providers must address the many comorbidities that are common in the aging population. Additional research will clarify how the processes of aging and HIV infection overlap and interact. This review addresses many of these important considerations.

The purpose of this investigation was to evaluate the diversity of bacteria in diabetic foot osteomyelitis using a 16S rRNA sequencing approach and to compare the results with conventional culture techniques. In this prospective observational study, we obtained 34 bone samples from patients admitted to our hospital with a moderate-severe diabetic foot infection. We analysed the distribution of the 16S rRNA gene sequences in the bone samples, using an Illumina MiSeq Personal Sequencer. We compared the genera that were detected with the cultured pathogens in the bone samples with conventional techniques. In the 23 samples that had positive results with both techniques, Staphylococcus, Corynebacterium, Streptococcus and Propionibacterium spp. were detected in 20, 18, 13 and 11 samples, respectively. Significantly more anaerobes were detected with 16S rRNA sequencing compared to conventional techniques (86.9 % vs. 23.1 %, p = 0.001) and more Gram-positive bacilli were present (78.3 % vs. 3.8 %, p

This study sought to assess the utility of monitoring response to treatment of diabetic foot osteomyelitis (DFO) with Tc‐99m WBC‐labelled single photon emission computed tomography (SPECT/CT) imaging. This is a retrospective cohort study of 20 patients with DFO with sequential Tc‐99m WBC‐labelled SPECT/CT imaging. Radiologic findings of osteomyelitis were evaluated and imaging results were correlated with clinical outcomes subtracted from chart review. Successful treatment of osteomyelitis was defined by wound healing and/or lack of re‐admission for bone infection of the same site within 1 year. The sensitivity, specificity, positive predictive value and negative predictive value of SPECT/CT to determine osteomyelitis treatment remission were 90%, 56%, 69% and 83%, respectively. Tc‐99m WBC‐labelled SPECT/CT imaging may be useful to help determine treatment outcomes for DFO.

Background Outpatient parenteral antimicrobial therapy (OPAT) is accepted as safe and effective for medically stable patients to complete intravenous (IV) antibiotics in an outpatient setting. Since, however, uninsured patients in the United States generally cannot afford OPAT, safety-net hospitals are often burdened with long hospitalizations purely to infuse antibiotics, occupying beds that could be used for patients requiring more intensive services. OPAT is generally delivered in one of four settings: infusion centers, nursing homes, at home with skilled nursing assistance, or at home with self-administered therapy. The first three—termed healthcare-administered OPAT (H-OPAT)—are most commonly used in the United States by patients with insurance funding. The fourth—self-administered OPAT (S-OPAT)—is relatively uncommon, with the few published studies having been conducted in the United Kingdom. With multidisciplinary planning, we established an S-OPAT clinic in 2009 to shift care of selected uninsured patients safely to self-administration of their IV antibiotics at home. We undertook this study to determine whether the low-income mostly non-English-speaking patients in our S-OPAT program could administer their own IV antimicrobials at home with outcomes as good as, or better than, those receiving H-OPAT. Methods and Findings Parkland Hospital is a safety-net hospital serving Dallas County, Texas. From 1 January 2009 to 14 October 2013, all uninsured patients meeting criteria were enrolled in S-OPAT, while insured patients were discharged to H-OPAT settings. The S-OPAT patients were trained through multilingual instruction to self-administer IV antimicrobials by gravity, tested for competency before discharge, and thereafter followed at designated intervals in the S-OPAT outpatient clinic for IV access care, laboratory monitoring, and physician follow-up. The primary outcome was 30-d all-cause readmission, and the secondary outcome was 1-y all-cause mortality. The study was adequately powered for readmission but not for mortality. Clinical, sociodemographic, and outcome data were collected from the Parkland Hospital electronic medical records and the US census, constituting a historical prospective cohort study. We used multivariable logistic regression to develop a propensity score predicting S-OPAT versus H-OPAT group membership from covariates. We then estimated the effect of S-OPAT versus H-OPAT on the two outcomes using multivariable proportional hazards regression, controlling for selection bias and confounding with the propensity score and covariates. Of the 1,168 patients discharged to receive OPAT, 944 (81%) were managed in the S-OPAT program and 224 (19%) by H-OPAT services. In multivariable proportional hazards regression models controlling for confounding and selection bias, the 30-d readmission rate was 47% lower in the S-OPAT group (adjusted hazard ratio [aHR], 0.53; 95% CI 0.35–0.81; p = 0.003), and the 1-y mortality rate did not differ significantly between the groups (aHR, 0.86; 95% CI 0.37–2.00; p = 0.73). The S-OPAT program shifted a median 26 d of inpatient infusion per patient to the outpatient setting, avoiding 27,666 inpatient days. The main limitation of this observational study—the potential bias from the difference in healthcare funding status of the groups—was addressed by propensity score modeling. Conclusions S-OPAT was associated with similar or better clinical outcomes than H-OPAT. S-OPAT may be an acceptable model of treatment for uninsured, medically stable patients to complete extended courses of IV antimicrobials at home., In a propensity score-balanced retrospective cohort study, Kavita Bhavan and colleagues compare health outcomes for patients undergoing self-administered versus healthcare-administered outpatient parenteral antimicrobial therapy., Editors' Summary Background Patients sometimes need lengthy courses of antimicrobial agents to treat life-threatening infections. For example, patients who develop endocarditis (an infection of the inner lining of the heart usually caused by bacteria entering the blood and traveling to the heart) need to be given antimicrobial drugs for up to six weeks. Initially, these patients require intensive diagnostic and therapeutic care in the hospital. But once the antimicrobial treatment starts to work, most patients only need regular intravenous antimicrobial infusions. Patients who stay in the hospital to receive this low intensity care occupy beds that could be used for patients requiring more intensive care. Moreover, they are at risk of catching a hospital-acquired, antibiotic-resistant infection. For these reasons, and because long-term administration of antimicrobial agents in the hospital is costly, outpatient parenteral (injected or infused) antimicrobial therapy (OPAT) is increasingly being used as a safe and effective way for medically stable patients to complete a course of intravenous antibiotics outside the hospital. Why Was This Study Done? In the US, OPAT is usually delivered in infusion centers, in nursing homes, or at home by visiting nurses. But healthcare-administered OPAT (H-OPAT) is available only to insured patients (in the US, medical insurance provided by employers or by the government-run Medicare and Medicaid programs funds healthcare). Uninsured people cannot usually afford H-OPAT and have to stay in safety-net hospitals (public hospitals that provide care to low-income, uninsured populations) for intravenous antibiotic treatment. In this propensity-score-balanced retrospective cohort study, the researchers investigate whether uninsured patients discharged from a safety-net hospital in Texas to self-administer OPAT at home (S-OPAT) can achieve outcomes as good as or better than those achieved by patients receiving H-OPAT. A retrospective cohort study compares recorded clinical outcomes in groups of patients who received different treatments. Because the patients were not chosen at random, such studies are subject to selection bias and confounding. Propensity score balancing is used to control for selection bias—the possibility that some members of the population are less likely to be included in a study than others. Adjustment for covariates (patient characteristics that may affect the outcome under study) is used to control for confounding—the possibility that unknown characteristics shared by patients with a specific outcome, rather than any treatment, may be responsible for that outcome. What Did the Researchers Do and Find? Between 2010 and 2013, 994 uninsured patients were enrolled in the hospital’s S-OPAT program, and 224 insured patients were discharged to an H-OPAT program. Patients in the S-OPAT group were trained to self-administer intravenous antimicrobials, tested for their ability to treat themselves before discharge, and then monitored by weekly visits to the S-OPAT outpatient clinic. The researchers estimated the effect of S-OPAT versus H-OPAT on 30-day all-cause readmission and one-year all-cause mortality (the primary and secondary outcomes, respectively) after adjusting for covariates and controlling for selection bias with a propensity score developed using baseline clinical and sociodemographic information collected from the patients. The 30-day readmission rate was 47% lower in the S-OPAT group than in the H-OPAT group (a significant result unlikely to have arisen by chance), and the one-year mortality rate did not differ significantly between the two groups. Notably, because the S-OPAT program resulted in patients spending fewer days having inpatient infusions, 27,666 inpatient days were avoided over the study period. What Do These Findings Mean? These findings indicate that, after adjusting for preexisting differences between those patients receiving S-OPAT and those receiving H-OPAT and for potential confounders, the risk of readmission within 30 days of discharge was lower in the S-OPAT group than in the H-OPAT group and the risk of dying within one year of hospital discharge did not differ significantly between the two groups (the study did not include enough participants to detect any subtle difference that might have existed for this end point). Thus, S-OPAT was associated with similar or better outcomes than H-OPAT. Note that there may be residual selection bias and confounding by characteristics not included in the propensity score. This study did not address whether S-OPAT actually improves outcomes for patients compared with H-OPAT; a randomized controlled trial in which patients are randomly assigned to receive the two treatments is needed to do this. Nevertheless, these findings suggest that S-OPAT might make it possible for uninsured, medically stable patients to have extended courses of intravenous antimicrobials at home rather than remaining in the hospital until their treatment is complete. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001922. The UK National Health Service Choices website provides basic information about the use of antibiotics, including information about when intravenous antibiotics are needed and about endocarditis The US National Heart, Lung, and Blood Institute also provides information about endocarditis and its treatment The Infectious Diseases Society of America provides clinical guidelines for the use of OPAT The OPAT Initiative of the British Society for Antimicrobial Chemotherapy is a multi-stakeholder project that supports the establishment of standardized OPAT services throughout the UK; it also provides guidelines for the use of OPAT Wikipedia has a page on propensity score matching (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)

Background. Biopsy specimens are often obtained in the evaluation of hematogenous vertebral osteomyelitis. The effect of prebiopsy antibiotic exposure on pathogen recovery is unknown. Methods. We conducted a retrospective cohort study of adult inpatients with hematogenous vertebral osteomyelitis at a tertiary care hospital from 1 January 2003 through 31 July 2007. Antibiotic exposure within 14 days before biopsy was evaluated. Results. Of 150 patients with hematogenous vertebral osteomyelitis, 92 (61%) underwent a biopsy (60 [65%] needle and 32 [35%] open biopsies). The median time from admission to biopsy was 3 days (range, 0–69 days). Patients who underwent biopsy were more likely to have weakness (53 [58%] biopsy vs 15 [26%] no biopsy; P , .001) and sensory loss (27 [29%] vs 6 [10%]; P 5 .006), but were less likely to have a positive blood culture result (28 [30%] vs 30 [52%]; P 5 .01). Pathogens were recovered in 61 patients (66%). Open biopsy had a higher yield than needle biopsy (29 [91%] of 32 vs 32 [53%] of 60; P , .001). Sixty patients (65%) who had biopsies performed received antibiotics

Background Vertebral osteomyelitis is a common manifestation of osteomyelitis in adults and associated with considerable morbidity. Limited data exist regarding hematogenous vertebral osteomyelitis. Our objective was to describe the epidemiology and management of hematogenous vertebral osteomyelitis. Methods We performed a 2-year retrospective cohort study of adult patients with hematogenous vertebral osteomyelitis at a tertiary care hospital. Results Seventy patients with hematogenous vertebral osteomyelitis were identified. The mean age was 59.7 years (±15.0) and 38 (54%) were male. Common comorbidities included diabetes (43%) and renal insufficiency (24%). Predisposing factors in the 30 days prior to admission included bacteremia (19%), skin/soft tissue infection (17%), and having an indwelling catheter (30%). Back pain was the most common symptom (87%). Seven (10%) patients presented with paraplegia. Among the 46 (66%) patients with a microbiological diagnosis, the most common organisms were methicillin-susceptible S. aureus [15 (33%) cases], and methicillin-resistant S. aureus [10 (22%)]. Among the 44 (63%) patients who had a diagnostic biopsy, open biopsy was more likely to result in pathogen recovery [14 (93%) of 15 with open biopsy vs. 14 (48%) of 29 with needle biopsy; p = 0.003]. Sixteen (23%) patients required surgical intervention for therapeutic purposes during admission. Conclusions This is one of the largest series of hematogenous vertebral osteomyelitis. A microbiological diagnosis was made in only approximately two-thirds of cases. S. aureus was the most common causative organism, of which almost half the isolates were methicillin-resistant.

Voriconazole is the preferred antifungal agent for Aspergillus infections. Therapeutic drug monitoring is recommended to achieve target concentrations and prevent toxicity. However, variable pharmacokinetics, cytochrome P450 polymorphisms, and extensive drug-drug interactions can contribute to subtherapeutic concentrations. We report a voriconazole “boosting” effect of omeprazole to achieve target concentrations for the treatment of Aspergillus in a patient who had persistently subtherapeutic trough concentrations.