Improving antimicrobial treatment in terms of antimicrobial stewardship and health costs by an OPAT service.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) is a standard for antimicrobial therapy internationally. With this prospective cohort study, we aimed to assess the impact of an OPAT service as part of antimicrobial stewardship (AMS) and evaluate the safety and efficiency of the program while illuminating the financial benefit for the hospital. METHODS: Socio-demographic data, treatment regimen and outcomes were prospectively recorded for all patients assigned to the program of the OPAT unit of the University Hospital of Zurich between November 2018 and September 2022. RESULTS: In total, we recorded 303 OPAT assignments of which 260 resulted in effective OPAT episodes. The 260 OPAT episodes were further optimized toward the choice of antimicrobial agent (n = 18) and length of therapy (n = 6). Moreover, OPAT resulted in alteration of patient assessment and care led by AMS strategies in 247 of 260 episodes (95%). While the bed days saved per year increased consistently with time, a total of 3934 in-hospital treatment days were saved amounting to a cost saving of 9,835,000 CHF over 47 months. Adverse events were recorded in 46 cases whilst only two of these have been the reason for readmission during OPAT treatment. Clinical cure was noted in 77% (199/260) and was negatively associated with Charlson Comorbidity Index (CCI; OR per 1 unit higher 0.85 (95% CI 0.78-0.93)). CONCLUSION: This study demonstrates the impact of an OPAT service in the framework of AMS as well as its benefits for the hospital whilst preserving safety and efficacy for the patient's parenteral antimicrobial treatment.

Mycobacterium tuberculosis infection associated immune perturbations correlate with antiretroviral immunity.

Infection with Mycobacterium tuberculosis (MTB) remains one of the most important opportunistic infections in people with HIV-1 (PWH). While active Tuberculosis (TB) leads to rapid progression of immunodeficiency in PWH, the interaction between MTB and HIV-1 during the asymptomatic phase of both infections remains poorly understood. In a cohort of individuals with HIV (PWH) with and without suppressed HIV-1 viral load, the transcriptomic profiles of peripheral blood mononuclear cells (PBMC) clustered in individuals infected with Mycobacterium tuberculosis (MTB) compared to carefully matched controls. Subsequent functional annotation analysis disclosed alterations in the IL-6, TNF, and KRAS pathways. Notably, MTB-associated genes demonstrated an inverse correlation with HIV-1 viremia, evident at both on individual gene level and when employed as a gene score. In sum, our data show that MTB infection in PWH is associated with a shift in the activation state of the immune system, displaying an inverse relationship with HIV-1 viral load. These results could provide an explanation for the observed increased antiretroviral control associated with MTB infection in PWH.

Low secondary attack rate after prolonged exposure to sputum smear positive miliary tuberculosis in a neonatal unit.

BACKGROUND: Several neonatal intensive care units (NICU) have reported exposure to sputum smear positive tuberculosis (TB). NICE guidelines give support regarding investigation and treatment intervention, but not for contact definitions. Data regarding the reliability of any interferon gamma release assay (IGRA) in infants as a screening test for TB infection is scarce. We report an investigation and management strategy and evaluated the viability of IGRA (T-Spot) in infants and its concordance to the tuberculin skin test (TST). METHODS: We performed an outbreak investigation of incident TB infection in a NICU after prolonged exposure to sputum smear positive miliary TB by an infant's mother. We defined individual contact definitions and interventions and assessed secondary attack rates. In addition, we evaluated the technical performance of T-Spot in infants and compared the results with the TST at baseline investigation. RESULTS: Overall, 72 of 90 (80%) exposed infants were investigated at baseline, in 51 (56.7%) of 54 (60%) infants, follow-up TST at the age of 6 months was performed. No infant in our cohort showed a positive TST or T-Spot at baseline. All blood samples from infants except one responded to phytohemagglutinin (PHA), which was used as a positive control of the T-Spot, demonstrating that cells are viable and react upon stimulation. 149 of 160 (93.1%) exposed health care workers (HCW) were investigated. 1 HCW was tested positive, having no other reason than this exposure for latent TB infection. 5 of 92 (5.5%) exposed primary contacts were tested positive, all coming from countries with high TB incidences. In total, 1 of 342 exposed contacts was newly diagnosed with latent TB infection. The secondary attack rate in this study including pediatric and adult contacts was 0.29%. CONCLUSION: This investigation highlighted the low transmission rate of sputum smear positive miliary TB in a particularly highly susceptible population as infants. Our expert definitions and interventions proved to be helpful in terms of the feasibility of a thorough outbreak investigation. Furthermore, we demonstrated concordance of T-Spot and TST. Based on our findings, we assume that T-Spot could be considered a reliable investigation tool to rule out TB infection in infants.

Spectrum of antibiotic resistance in UTI caused by Escherichia coli among HIV-infected patients in Uganda: a cross-sectional study.

BACKGROUND: Antimicrobial drug resistance is one of the top ten threats to global health according to the World Health Organization. Urinary tract infections (UTIs) are among the most common bacterial infections and main reason for antibiotic prescription. The incidence of UTIs appears to be high among people living with HIV. We sought to determine the most common UTI pathogens among HIV infected patients and evaluate their susceptibility towards antibiotics. METHODS: We performed a cross-sectional study among HIV-infected patients aged ≥ 18 years presenting at an HIV care specialized clinic with symptoms suggestive of a urethritis. Urine cultures were subjected to antibiotic susceptibility testing according to Clinical Laboratory Standards Institute. The data was analyzed using STATA, we performed Pearson's Chi-square and Fisher's exact tests to compare differences between proportions. RESULTS: Out of the 200 patients, 123 (62%) were female. The median age was 41.9 years (IQR 34.7-49.3). Only 32 (16%) urine cultures showed bacterial growth. Escherichia coli was the most commonly isolated uropathogen (72%), followed by Klebsiella pneumoniae (9%). E. coli was completely resistant to cotrimoxazole and ampicillin; resistance to ciprofloxacin and ceftriaxone was 44% and 35% respectively; 9% to gentamicin; no resistance detected to nitrofurantoin and imipenem. CONCLUSIONS: Our findings are congruent with the Uganda national clinical guidelines which recommends nitrofurantoin as the first line antibiotic for uncomplicated UTI. Significant ciprofloxacin and ceftriaxone resistance was detected. In the era of emerging antibiotic resistance, understanding the local susceptibilities among sub-populations such as HIV infected patients is crucial. Further investigation is needed to address reasons for the low bacterial growth rate observed in the urine cultures.

Approach for tuberculosis-associated immune reconstitution inflammatory syndrome in an HIV-negative patient.

A male refugee from the Middle East was diagnosed with pulmonary tuberculosis and Pott's disease with paravertebral abscess. After starting the standard regimen, the sputum culture converted to negative and the patient's general condition improved. Six weeks later, the patient presented with clinical worsening of known symptoms, new appearance of focal neurological deficits and progress of radiological features showing progression of the paravertebral abscess. Immune reconstitution inflammatory syndrome with Mycobacterium tuberculosis (TB-IRIS) was presumed, and treatment with high-dose steroids was started. Due to recurrent relapses while tapering, corticosteroids had to be given over a prolonged period. After treatment completion, the patient was in a good general condition, abscesses had decreased and neurological deficits were in complete remission. This case presents the rare manifestation of TB-IRIS in HIV-negative patients and its management in a high-income country.

'Out of sight, out of mind?' A follow-up on HIV-infected patients with drug-resistant pulmonary tuberculosis in Uganda: A case series.

Among new tuberculosis cases in Uganda, 10.3% are drug-resistant and 43% occur in people living with HIV. Both resistance and HIV-tuberculosis co-infection lead to unfavourable tuberculosis treatment outcomes. In this case series, we followed up eight HIV-tuberculosis co-infected patients withdrawn from a pharmacokinetics study on anti-tuberculosis drugs between April 2013 and April 2015 following a diagnosis of drug-resistant tuberculosis. We identified resistance patterns and treatment regimens and evaluated their tuberculosis treatment outcomes. Two patients were multidrug-resistant, only one out of eight was treated according to the World Health Organization guidelines applicable at that time and five had unfavourable tuberculosis treatment outcomes, that is, were lost to follow-up, could not be evaluated or died. Taken together, we found unfavourable tuberculosis treatment outcomes for patients with drug-resistant tuberculosis. This indicates the necessity of implementation of current treatment guidelines and close monitoring for patients with drug-resistant tuberculosis.

PET/CT in therapy control of infective native aortic aneurysms.

Infective native aortic aneurysms (INAA) are aneurysms arising from infection of the aortic wall. Treatment is demanding with 5-year survival rates between 53 and 55%. The aim of our study was to evaluate the usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the long-term monitoring of patients with proven INAA. Fifty-three PET/CT were performed in 15 patients with INAA in this single-center retrospective cohort study and retrospective analysis of prospectively collected Vascular Graft Cohort Study (VASGRA) data. Median metabolic activity (as measured by maximum standardized uptake value, SUVmax) of the aneurysms at the initial PET/CT was high (6.8 (IQR 5.7-21.8)), and lower at the last PET/CT prior to the end of antimicrobial therapy (3.9 (IQR 2.7-6.8); n = 11) as well as in the first PET/CT after the end of the treatment (3.9 (IQR 3.0-4.4);n = 6). Compared to the course of C-reactive protein alone, PET/CT provided different (> 20% difference in trend) or altering (opposed trend) information on the course of disease in at least 14 comparisons (56%) in 11 patients (73%). The one-year and five-year freedom from all-cause lethality was 92% (95% confidence interval 57%-99%). As compared to the course of C-reactive protein, PET/CT provides different and occasionally altering information in therapy control of INAA.

An immunocompetent farmer with isolated cerebral alveolar echinococcosis: illustrative case.

BACKGROUND: Alveolar echinococcosis is a rare condition, but living or working in a rural environment is a substantial risk factor. The liver is the organ primarily affected, with additional extrahepatic manifestations in approximately 25% of cases. Primary extrahepatic disease is rare, and isolated cerebral involvement is extremely unusual. OBSERVATIONS: The authors described an illustrative case of isolated cerebral alveolar echinococcosis in an immunocompetent farmer. Magnetic resonance imaging of the brain showed a predominantly cystic lesion with perifocal edema and a "bunch of grapes" appearance in the left frontal lobe. Histology revealed sharply demarcated fragments of a fibrous cyst wall accompanied by marked inflammation and necrosis. Higher magnification showed remnants of protoscolices with hooklets and calcified corpuscles. Immunohistochemistry and polymerase chain reaction (PCR) analysis confirmed the diagnosis of cerebral alveolar echinococcosis. Interestingly, serology and thoracic and abdominal computed tomography results were negative, indicative of an isolated primary extrahepatic manifestation. LESSONS: Isolated, primary central nervous system echinococcosis is extremely rare, with only isolated case reports. As in the authors' case, it can occur in immunocompetent patients, especially persons with a rural vocational history. Negative serology results do not exclude cerebral echinococcosis, which requires histological confirmation. Immunohistochemical staining and PCR analysis are especially useful in cases without classic morphological findings.

Rising temperature and its impact on receptivity to malaria transmission in Europe: A systematic review.

BACKGROUND: Malaria is one of the most life-threatening vector-borne diseases globally. Recent autochthonous cases registered in several European countries have raised awareness regarding the threat of malaria reintroduction to Europe. An increasing number of imported malaria cases today occur due to international travel and migrant flows from malaria-endemic countries. The cumulative factors of the presence of competent vectors, favourable climatic conditions and evidence of increasing temperatures might lead to the re-emergence of malaria in countries where the infection was previously eliminated. METHODS: We performed a systematic literature review following PRISMA guidelines. We searched for original articles focusing on rising temperature and the receptivity to malaria transmission in Europe. We evaluated the quality of the selected studies using a standardised tool. RESULTS: The search resulted in 1'999 articles of possible relevance and after screening we included 10 original research papers in the quantitative analysis for the systematic review. With further increasing temperatures studies predicted a northward spread of the occurrence of Anopheles mosquitoes and an extension of seasonality, enabling malaria transmission for annual periods up to 6 months in the years 2051-2080. Highest vector stability and receptivity were predicted in Southern and South-Eastern European areas. Anopheles atroparvus, the main potential malaria vector in Europe, might play an important role under changing conditions favouring malaria transmission. CONCLUSION: The receptivity of Europe for malaria transmission will increase as a result of rising temperature unless socioeconomic factors remain favourable and appropriate public health measures are implemented. Our systematic review serves as an evidence base for future preventive measures.

Diagnostic Accuracy of PET/CT and Contrast Enhanced CT in Patients With Suspected Infected Aortic Aneurysms.

OBJECTIVE: Infected aortic aneurysms are highly lethal, and management is very demanding, requiring an early diagnosis. The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT) and contrast enhanced CT (CE-CT) in patients with suspected infected aortic aneurysms. METHODS: PET/CT was performed in patients with clinically suspected infected aortic aneurysms, and additional CE-CT was performed if feasible. Diagnostic accuracy was assessed by two independent readers using a four point grading score for both imaging modalities. Maximum standardised uptake values (SUVmax) were calculated for quantitative measurements of metabolic activity in PET/CT. The reference standard was a combination of clinical presentation, laboratory findings, and imaging. RESULTS: Ten patients were included prospectively in the study, 24 retrospectively; 16 patients (47%) prior to the start of antimicrobial treatment and all 34 patients prior to any vascular intervention. Thirteen of the 34 patients had an infected aortic aneurysm (38%). Proven infected aortic aneurysms were all metabolically active on PET/CT with a median SUVmax of 6.6 (interquartile range 4.7-21.8). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for the diagnosis of infected aortic aneurysm was 100%, 71%, 68%, 100%, and 82%, for reader 1 and 85%, 71%, 65%, 88%, and 77%, for reader 2. Respective values for CE-CT, performed in 20 patients (59%), were 63%, 75%, 63%, 75%, and 70%, for reader 1 and 88%, 50%, 54%, 86%, and 65%, for reader 2. CONCLUSION: The diagnostic accuracy of PET/CT in the detection of infected aortic aneurysms (n = 13) is high, and higher than CE-CT. While PET/CT demonstrates an excellent sensitivity, its specificity is hampered because of false positive findings.

Ten years of antiretroviral therapy: Incidences, patterns and risk factors of opportunistic infections in an urban Ugandan cohort.

BACKGROUND: Despite increased antiretroviral therapy (ART) coverage and the raised CD4 threshold for starting ART, opportunistic infections (OIs) are still one of the leading causes of death in sub-Saharan Africa. There are few studies from resource-limited settings on long-term reporting of OIs other than tuberculosis. METHODS: Patients starting ART between April 2004 and April 2005 were enrolled and followed-up for 10 years in Kampala, Uganda. We report incidences, patterns and risk factors using Cox proportional hazards models of OIs among all patients and among patients with CD4 cell counts >200 cells/µL. RESULTS: Of the 559 patients starting ART, 164 patients developed a total of 241 OIs during 10 years of follow-up. The overall incidence was highest for oral candidiasis (25.4, 95% confidence interval (CI): 20.5-31.6 per 1000 person-years of follow-up), followed by tuberculosis (15.3, 95% CI: 11.7-20.1), herpes zoster (12.3, 95% CI: 9.1-16.6) and cryptococcal meningitis (3.0, 95% CI: 1.7-5.5). Incidence rates for all OIs were highest in the first year after ART initiation and decreased with the increase of the current CD4 cell count. Factors independently associated with development of OIs were baseline nevirapine-based regimens, time-varying higher viral load, time-varying lower CD4 cell count and time-varying lower hemoglobin. In patients developing OIs at a current CD4 cell count >200 cells/µL, factors independently associated with OI development were time-varying increase in viral load and time-varying decrease in hemoglobin, whereas a baseline CD4 cell count <50 cells/µL was protective. CONCLUSION: We report high early incidences of OIs, decreasing with increasing CD4 cell count and time spent on ART. Ongoing HIV replication and anemia were strong predictors for OI development independent of the CD4 cell count. Our findings support the recommendation for early initiation of ART and suggest close monitoring for OIs among patients recently started on ART, with low CD4 cell count, high viral load and anemia.