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Background Management and control of coronavirus disease 2019 (COVID-19) relies on reliable diagnostic testing. Objectives To evaluate the diagnostic test accuracy (DTA) of nucleic acid amplification tests (NAATs) for the diagnosis of coronavirus infections. Data sources PubMed, Web of Science, the Cochrane Library, Embase, Open Grey and conference proceeding until May 2019. PubMed and medRxiv were updated for COVID-19 on 31st August 2020. Study eligibility Studies were eligible if they reported on agreement rates between different NAATs using clinical samples. Participants Symptomatic patients with suspected upper or lower respiratory tract coronavirus infection. Methods The new NAAT was defined as the index test and the existing NAAT as reference standard. Data were extracted independently in duplicate. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Confidence regions (CRs) surrounding summary sensitivity/specificity pooled by bivariate meta-analysis are reported. Heterogeneity was assessed using meta-regression. Results Fifty-one studies were included, 22 of which included 10 181 persons before COVID-19 and 29 including 8742 persons diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall summary sensitivity was 89.1% (95%CR 84.0–92.7%) and specificity 98.9% (95%CR 98.0–99.4%). Nearly all the studies evaluated different PCRs as both index and reference standards. Real-time RT PCR assays resulted in significantly higher sensitivity than other tests. Reference standards at high risk of bias possibly exaggerated specificity. The pooled sensitivity and specificity of studies evaluating SARS-COV-2 were 90.4% (95%CR 83.7–94.5%) and 98.1% (95%CR 95.9–99.2), respectively. SARS-COV-2 studies using samples from the lower respiratory tract, real-time RT-PCR, and tests targeting the N or S gene or more than one gene showed higher sensitivity, and assays based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP), especially when targeting only the RNA-dependent RNA polymerase (RdRp) gene, showed significantly lower sensitivity compared to other studies. Conclusions Pooling all studies to date shows that on average 10% of patients with coronavirus infections might be missed with PCR tests. Variables affecting sensitivity and specificity can be used for test selection and development.

In recent years, there have been significant developments in rapid diagnostic techniques (RDTs) in microbiology for the diagnosis of infectious diseases. By providing a more rapid diagnosis, RDTs have the potential to affect diagnostic algorithms and therapeutic decisions. In addition to “antibiotic stewardship,” the term “diagnostic stewardship” has recently been coined in clinical practice and denotes the promotion of a rational implementation of diagnostic tests with a view to improving the quality of care and safely reducing cost. This review explores the advancement of diagnostic and antibiotic stewardship in the implementation of RDTs and describes the most relevant related clinical applications in Clostridioides difficile infections (CDIs), bloodstream infections (BSIs), and respiratory infections. An innovative evidence-based RDT diagnostic algorithm that varies according to the presence of pre-agreed institutional criteria significantly increases testing accuracy for differentiating CDIs from carriage status. Evidence on BSIs reveals that pairing RDTs and antibiotic stewardship eases timely and appropriate utilization of RDTs results that may improve the clinical outcomes by optimizing antibiotic use. Data on clinical implications of RDTs targeting antibiotic-resistant Gram-negative and respiratory infections are scarce and inconclusive. Intertwining the role of diagnostic and antibiotic stewardship is crucial to optimizing RDTs utilization, by ensuring that RDTs are rationally selected and implemented, and results correctly interpreted and applied to clinical practice. Further research is needed to explore the clinical implications of RDT implementation.

Background A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19. Methods Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values. Results A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66–0.81) for predicting disease progression by day-11. Conclusion An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians’ decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.

Background: A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19.Methods: Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or ICU and/or respiratory failure (PaO2/FiO2 ratioResults: A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age >65 years, dyspnea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) showed an AUC of 0.73 (95%CI: 0.66 - 0.81) for predicting disease progression by day-11. Conclusion: An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate assessment of clinicians’ decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.

Background: A major limitation of predictive prognostic models in COVID-19 patients is the heterogeneity of disease stage and population. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression within 11 days in hospitalized COVID-19 patients. Methods: Single-centre, prospective cohort study on hospitalized adult COVID-19 patients. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day-5, -10, and -15 from symptoms onset and in case of intensive care unit (ICU) admission, discharge, or death. COVID-19 progression was defined as in-hospital death and/or ICU and/or respiratory failure (PaO2/FiO2 ratio65 years, cardiovascular disease, and at least three abnormal laboratory parameters among CRP > 80 U/L, AST > 45 U/L, ALT > 40 U/L, NLR > 4·5, LDH > 250 U/L, and CK > 80 U/L showed an AUC of 0·73 (95%CI: 0·66 - 0·81) for predicting disease progression. Conclusion: An easy-to-use panel of laboratory/clinical parameters computed at day-5 from symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 from symptoms onset could facilitate clinicians’ decision making and be used to increase patient population in clinical trials in hospitalized patients. Trial Registration: COVID 19-VR registry (ClinicalTrials.gov NCT04497194). Funding Statement: This study is part of React-COVID-19 project funded by Fondazione CARIVERONA. Declaration of Interests: The authors have no conflict of interests to be declared. Ethics Approval Statement: The study was approved by the hospital Institutional Review Board (IRB 2577CESC).

Background: Point-of-care tests could be essential in differentiating bacterial and viral acute communityacquired lower respiratory tract infections and driving antibiotic stewardship in the community. Objectives: To assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections. Data sources: Multiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions. Study eligibility criteria: Diagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute communityacquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori. Assessment of risk of bias: Four investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2. Methods of data synthesis: The measures of diagnostic test accuracy were calculated with 95% CI. Results: A total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%-84%) but high specificity (>80%). Discussion: Physical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the patho-gens considered were found to be the most accurate. Elisa Gentilotti, Clin Microbiol Infect 2022;28:13 (c) 2021 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Background Surgical site infections are a leading cause of morbidity and mortality after caesarean section, especially in Low and Middle Income Countries. We hypothesized that a combined infection prevention and control with antimicrobial stewardship joint program would decrease the rate of post- caesarean section surgical site infections at the Obstetrics & Gynaecology Department of a Tanzanian tertiary hospital. Methods The intervention included: 1. formal and on-job trainings on infection prevention and control; 2. evidence-based education on antimicrobial resistance and good antimicrobial prescribing practice. A second survey was performed to determine the impact of the intervention. The primary outcome of the study was post-caesarean section surgical site infections prevalence and secondary outcome the determinant factors of surgical site infections before/after the intervention and overall. The microbiological characteristics and patterns of antimicrobial resistance were ascertained. Results Total 464 and 573 women were surveyed before and after the intervention, respectively. After the intervention, the antibiotic prophylaxis was administered to a significantly higher number of patients (98% vs 2%, p p = 0.001), with higher rates of Pfannenstiel skin incisions (29% vs 18%, p p p Staphylococus aureus was detected in the post-intervention survey. Conclusions Further researches are needed to better understand the potential of a hospital-based multidisciplinary approach to surgical site infections and antimicrobial resistance prevention in resource-constrained settings.

Background: The COVID-19 pandemic has resulted in many health systems worldwide facing an imbalance between patients’ need and available resources. No previous studies have developed explicit recommendations for selecting patients most likely to benefit from hospitalisation in settings with an unsolvable hospital-bed shortage. Methods: Multi-Criteria Decision Analysis (MCDA) was used to determine weights for criteria to prioritise COVID-19 patients for admission to hospital. The MCDA was applied in two main steps: specification of criteria for prioritising COVID-19 patients, and levels within each criterion; and determination of weights for the criteria based on experts’ knowledge and experience in managing COVID-19 patients, via an online survey. Criteria were selected based on available COVID-19 evidence with a focus on healthcare settings with limited resources. Findings: Eleven criteria for prioritising patients were specified, and 103 MDs caring for COVID-19 patients completed the survey to determine the criteria’s weights. The 11 criteria (and levels), in decreasing order of importance [mean weights, summing to 100%], are: PaO2 (>80, 70-80, and 96%, 92-96%, and 20 breaths/min) [9∙5%]; comorbidities (diabetes, respiratory/cardiovascular diseases, and onco-haematological diseases) [6.5%]; living with vulnerable people (people with comorbidities, pregnant women, and immunosuppressed patients) [6∙4%]; body mass index ( 40) [5∙6%]; duration of symptoms before hospital evaluation ( 7 days) [5∙4%]; CRP (normal / high based on local cut off) [5∙1%]; and age (18-50, 50-70, and >70) [3∙8%]. Interpretation: MCDA can be used for prioritising patients for hospitalisation when prioritisation is necessary and evidence for disease predictors is limited or unavailable. MCDA is likely to be especially useful in low- and middle-income countries where effective national contingency plans are difficult to establish. Funding Statement: This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 820755. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and bioMerieux SA, Janssen Pharmaceutica NV, Accelerate Diagnostics S.L., Abbott, Bio-Rad Laboratories, BD Switzerland Sarl, and The Wellcome Trust Limited. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: There were no humans participating in the research project. Briefly, in the study a list of variables/criteria W ere selected from the scientific literature and the Multi-Criteria Decision Analysis (based on PAPRIKA method) was applied in order to give a weight/score (total 100%) to each criterion. For this reason, the study was exempted from ethical review/clearance.

P. jiroveci (Pj) causes a potentially fatal pneumonia in immunocompromised patients and the factors associated with a bad outcome are poorly understood. A retrospective analysis on Pj pneumonia (PjP) cases occurring in Tor Vergata University Hospital, Italy, during the period 2011-2015. The patients' demographic, clinical and radiological characteristics and the Pj genotypes were considered. The study population included 116 patients, 37.9% of whom had haematological malignancy or underwent haematological stem cell transplantation (HSCT), 22.4% had HIV infection, 16.4% had chronic lung diseases (CLD), 7.8% had a solid cancer, and 3.4% underwent a solid organ transplant (SOT). The remaining 12.1% had a miscellaneous other condition. At univariate analysis, being older than 60 years was significantly correlated with a severe PjP (OR [95%CI] 2.52 [0.10-5.76]; p = 0.031) and death (OR [95%CI] 2.44 [1.05-5.70]; p = 0.036), while a previous trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were significantly associated with a less severe pneumonia (OR[95%CI] 0.35 [0.15-0.84], p = 0.023); moreover, death due to PjP was significantly more frequent in patients with CLD (OR[95%CI] 3.26 [1.17-9.05]; p = 0.019) while, admission to the Infectious Diseases Unit was significantly associated with fewer deaths (OR[95%CI] 0.10 [0.03-0.36], p = 0.002). At multivariate analysis, a better PjP outcome was observed in patients taking TMP/SMX prophylaxis and that were admitted to the Infectious Diseases Unit (OR[95%CI] 0.27 [0.07-1.03], p = 0.055, OR[95%CI] 0.16 [0.05-0.55]; p = 0.004, respectively). In conclusion, in our study population, TMP/SMX prophylaxis and infectious disease specialist approach were variables correlated with a better PjP outcome.

Background Surgical site infection (SSI) is a common post-operative complication causing significant morbidity and mortality. Many SSI occur after discharge from hospital. Post-discharge SSI surveillance in low and middle income countries needs to be improved. Methodology We conducted an observational cohort study in Dodoma, Tanzania to examine the sensitivity and specificity of telephone calls to detect SSI after discharge from hospital in comparison to a gold standard of clinician review. Women undergoing caesarean section were enrolled and followed up for 30 days. Women providing a telephone number were interviewed using a structured questionnaire at approximately days 5, 12 and 28 post-surgery. Women were then invited for out-patient review by a clinician blinded to the findings of telephone interview. Results A total of 374 women were enrolled and an overall SSI rate of 12% (n = 45) was observed. Three hundred and sixteen (84%) women provided a telephone number, of which 202 had at least one telephone interview followed by a clinical review within 48 h, generating a total of 484 paired observations. From the clinical reviews, 25 SSI were diagnosed, of which telephone interview had correctly identified 18 infections; telephone calls did not incorrectly identify SSI in any patients. The overall sensitivity and specificity of telephone interviews as compared to clinician evaluation was 72 and 100%, respectively. Conclusion The use of telephone interview as a diagnostic tool for post-discharge surveillance of SSI had moderate sensitivity and high specificity in Tanzania. Telephone-based detection may be a useful method for SSI surveillance in low-income settings with high penetration of mobile telephones.

OBJECTS: The impact of HIV-1 tropism on the emergence of non-AIDS events was evaluated in a cohort of 116 antiretroviral (ART) responder patients. METHODS: The patients were followed for the emergence of hypertension, renal impairment, metabolic and bone disorders (defined as non-AIDS events) each 8 weeks at standard visits. A V3 plasma sequence genotype analysis was performed at the time of ART initiation and the geno2pheno algorithm with the results that defines the false positive rate (FPR) was used to infer HIV tropism. The associations between the non-AIDS events and the FPR at baseline were evaluated using the Chi-squared test for trend. A Cox regression analysis using the counting process formulation of Andersen and Gill was performed to define whether the emergence of non-AIDS events was correlated to FPR. RESULTS: The prevalence of at least one non-AIDS event resulted higher in patients with a FPR

Few data are available on the determinants and characteristics of post-caesarean section (CS) surgical site infections (SSIs) in resource-limited settings. We conducted a prospective observational cohort study to evaluate the rates, determinants, and microbiological characteristics of post-CS SSI at the Dodoma Regional Referral Hospital (DRRH) Gynaecology and Obstetrics Department in Tanzania. Spanning a three-month period, all pregnant women who underwent CS were enrolled and followed up for 30 days. SSI following CS occurred in 224 (48%) women. Only 10 (2.1%) women received pre-incision antibiotic prophylaxis. Urgent intervention is needed to prevent and control infections and contain the rising rate of post-CS SSI at the DRRH.

In 2013, an estimated 1.5 million HIV-positive pregnant women gave birth, with 240,000 children worldwide acquiring HIV. More than 90% of new pediatric infections occurred in Sub-Saharan Africa. The latest WHO guidelines recommended efavirenz (EFV)-based antiretroviral therapy as the first-line regimen for prevention of mother-to-child transmission of HIV (PMTCT). On the other hand, some data suggest that nevirapine (NVP), a well-known antiretroviral, could still play a relevant role in PMTCT, especially in resource-limited settings (RLSs) where the fertility rate is dramatically high compared to developed countries. Given the lack of an unanimous consensus and definitive opinions, this paper goes through the reasons for WHO decisions and aims at refreshing the debate about NVP and EFV pros and cons for PMTCT in RLSs.

It has been shown that P-glycoprotein (P-gp) can greatly affect the cell uptake of antiretroviral drugs, thus hampering their access to HIV-1 replication sites. Lymphocytes are important sites of replication of HIV and target of other drugs, modification on these cells of P-gp could have an effect on pharmacokinetic of antiretrovirals and drug substrates. Blood samples from 16 healthy volunteers were used to determine the expression of P-gp on total, T and T helper lymphocytes after exposure to darunavir, a second generation protease inhibitor, and raltegravir, the first approved integrase inhibitor. Moreover, the effect of the drugs on P-gp functional activity was also studied by the rhodamine-123 efflux test. Darunavir, but not raltegravir, exposure caused a moderate, dose-dependent increment in P-gp expression in total, T and T helper lymphocytes, as demonstrated by the relative frequency of P-gp + cells and by the amount of P-gp molecules present on cell surface. Functionally, incubation with darunavir led to a marked inhibition of P-gp activity measured by the efflux of rhodamine-123 similar to that observed by verapamil, a specific P-gp inhibitor. Raltegravir was not able to modify the efflux of rhodamine-123 level. Data show that darunavir, unlike raltegravir, may modify the expression and functionality of P-gp on human lymphocytes, thus leading to potential changes in intracellular concentrations of darunavir in patients treated with other drugs substrate of P-gp and vice versa. Our study highlights the need for studies on drug interactions via the P-gp modulation mechanism, especially with the current multi-drug regimens.

Anti-tumor necrosis factor alpha (anti-TNF-α) is used in the treatment of rheumatic diseases not responsive to first-line regimens. Data on the safety of anti-TNF-α in HIV-infected patients are scarce and conflicting. We describe a case of septic shock and multiorgan failure that occurred after etanercept initiation and influenza vaccination in an HIV-infected woman with rheumatoid arthritis.

Background Liver disease is the second cause of death among HIV patients receiving highly active antiretroviral therapy (HAART) in Europe. HIV patients have a high prevalence of chronic HBV (6–10%) and HCV (33%) co-infection, and accelerated progression of viral hepatitis. Furthermore, the long duration of both HIV and HCV diseases in the HAART era increases the risk of hepatocellular carcinoma. Findings We report the case of a 49 year -old HIV/HCV co-infected male patient who developed hepatocellular carcinoma. The patient underwent a partial hepatectomy, and a few months later was treated with transcatheter arterial chemoembolisation due to hepatocarcinoma recurrence. Two months later, advanced hepatocellular carcinoma was diagnosed and sorafenib therapy was initiated. The patient achieved partial response of the main lesions, complete regression of the smallest lesions and did not experience clinical progression during the 20-month follow-up period. During therapy with sorafenib, the patient was treated with HAART with good viral and immunological responses. We used the therapeutic drug monitoring to assess antiretroviral concentrations during co-administration of sorafenib. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines. No grade 3 or 4 toxicities were observed. At month 20 of treatment, new liver lesions with portal vein thrombosis were diagnosed. After 28 months of sorafenib therapy, the patient deceased for severe liver insufficiency. Conclusions Sorafenib monotherapy demonstrated a marked delay in HCC disease progression in an HIV/HCV co-infected patient. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines, suggesting a possible interaction.

Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine. The patient presented with fever, headache, and arthromyalgia after returning from Central African Republic where he had been working. The blood examination revealed acute renal failure, thrombocytopaenia and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria according to the laboratory WHO criteria was diagnosed. A treatment with quinine and doxycycline for the first 12 hours was initially administered, followed by arthemeter/lumefantrine (Riamet®) for a further three days. At day 10, a diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l). Hereditary and autoimmune disorders and other infections were excluded through bone marrow aspiration, total body TC scan and a wide panel of molecular and serologic assays. The patient was treated by transfusion of six units of packed blood red cell. He was discharged after complete remission at day 25. At present, the patient is in a good clinical condition and there is no evidence of haemolytic anaemia recurrence. This is the first report of haemolytic anaemia probably associated with oral artemether/lumefantrine. Further research is warranted to better define the adverse events occurring during combination therapy with artemisinin derivatives.

Adherence to Highly Active Antiretroviral Therapy can be affected by a number of factors limiting the outcome of the treatment. We report the case of a 39 year-old HIV-HCV co-infected woman in stable virologic suppression and immune recovery during a raltegravir plus unboosted atazanavir dual-therapy taken every other day. Measurement of HIV-1 RNA plasma levels (viral load), CD4+ T-cell counts and the therapeutic drug monitoring through validated high-performance liquid chromatography methods, were performed to assess the effectiveness of this regimen. Our data on raltegravir pharmacokinetics in association with atazanavir show adequate minimum effective concentrations of raltegravir throughout 36 and 48 hours despite the every other day intake of the drug. Further studies are recommended in order to identify the determinants that could enable a reduction in antiretroviral dosing frequency in case of difficult management of HIV-infected patients due to low adherence to therapy. By reporting our medical experience, we focused on the utility of performing therapeutic drug monitoring especially in cases of poor adherence, drug and/or alcohol abuse, co morbidities and co-administration of other drugs.

Introduction Prosthetic joint infection due to Mycobacterium tuberculosis is occasionally encountered in clinical practice. To the best of our knowledge, this is the first report of a prosthetic joint infection due to Mycobacterium tuberculosis complicated by psoas abscesses and secondary Addison disease. Case presentation A 67-year-old immunocompetent Caucasian woman underwent total left hip arthroplasty because of osteoarthritis. After 18 months, she underwent arthroplasty revision for a possible prosthetic infection. Periprosthetic tissue specimens for bacteria were negative, and empirical antibiotic therapy was unsuccessful. She was then admitted to our department because of complications arising 22 months after arthroplasty. A physical examination revealed a sinus tract overlying her left hip and skin and mucosal pigmentation. Her levels of C-reactive protein, basal cortisol, adrenocorticotropic hormone, and sodium were out of normal range. Results of the tuberculin skin test and QuantiFERON-TB Gold test were positive. Computed tomography revealed a periprosthetic abscess and the inclusion of the left psoas muscle. Results of microbiological tests were negative, but polymerase chain reaction of a specimen taken from the hip fistula was positive for Mycobacterium tuberculosis. Our patient's condition was diagnosed as prosthetic joint infection and muscle psoas abscess due to Mycobacterium tuberculosis and secondary Addison disease. She underwent standard treatment with rifampicin, ethambutol, isoniazid, and pyrazinamide associated with hydrocortisone and fludrocortisone. At 15 months from the beginning of therapy, she was in good clinical condition and free of symptoms. Conclusions Prosthetic joint infection with Mycobacterium tuberculosis is uncommon. A differential diagnosis of tuberculosis should be considered when dealing with prosthetic joint infection, especially when repeated smears and histology examination from infected joints are negative. Clinical outcomes of prosthetic joint infection by Mycobacterium tuberculosis are unpredictable, especially given the limited literature in this field and the uncertainty of whether medical treatment alone can eradicate the infection without prosthesis removal. Furthermore, this case report raises interesting issues such as the necessity of a follow-up evaluation after treatment based on clinical conditions, the utility of a more standardized length of treatment for periprosthetic tuberculous infection, and the importance of a high diffusion capacity of anti-mycobacterial agents in order to eradicate the infection.

Graphical Abstract, Highlights • Multi-Criteria Decision Analysis applied to SARS CoV-2 pandemic • Creating a model to prioritize hospitalization of COVID-19 patients in low- and middle-income countries • Eleven criteria selected considering their feasibility in low-resource settings • Reducing the risk of non-standardised approaches and improving the response of health systems to new pandemics, Objective To use Multi-Criteria Decision Analysis (MCDA) to determine weights for eleven criteria in order to prioritize COVID-19 non-critical patients for admission to hospital in healthcare settings with limited resources. Methods The MCDA was applied in two main steps: specification of criteria for prioritizing COVID-19 patients (and levels within each criterion); and determination of weights for the criteria based on experts’ knowledge and experience in managing COVID-19 patients, via an online survey. Criteria were selected based on available COVID-19 evidence with a focus on low- and middle-income countries (LMICs). Results The most important criteria (mean weights, summing to 100%), are: PaO2 (16.3%); peripheral O2 saturation (15.9%); chest X-ray (14.1%); Modified Early Warning Score-MEWS (11.4%); respiratory rate (9.5%); comorbidities (6.5%); living with vulnerable people (6.4%); body mass index (5.6%); duration of symptoms before hospital evaluation (5.4%); CRP (5.1%); and age (3.8%). Conclusions At the beginning of a new pandemic, when evidence for disease predictors is limited or unavailable and effective national contingency plans are difficult to establish, the MCDA prioritization model could play a pivotal role in improving the response of health systems.

Background In recent years, Nocardia farcinica has been reported to be an increasingly frequent cause of localized and disseminated infections in the immunocompromised patient. However, recent literature is limited. We report a case of left thigh phlegmon caused by N. farcinica that occurred in a patient with Leprosy undergoing treatment with prednisone for leprosy reaction. Case presentation We describe the case of left thigh phlegmon caused by Nocardia farcinica in a 54-year-old Italian man affected by multi-bacillary leprosy. The patient had worked in South America for 11 years. Seven months after his return to Italy, he was diagnosed with Leprosy and started multi-drug antibiotic therapy plus thalidomide and steroids. Then, during therapy with rifampicin monthly, minocycline 100 mg daily, moxifloxacin 400 mg daily, and prednisone (the latter to treat type 2 leprosy reaction), the patient complained of high fever associated with erythema, swelling, and pain in the left thigh. Therefore, he was admitted to our hospital with the clinical suspicion of cellulitis. Ultrasound examination and Magnetic Resonance Imaging showed left thigh phlegmon. He was treated with drainage and antibiotic therapy (meropenem and vancomycin replaced by daptomycin). The responsible organism, Nocardia farcinica, was identified by 16S rRNA sequencing in the purulent fluid taken out by aspiration. The patient continued treatment with intravenous trimethoprim/sulfamethoxazole and imipenem followed by oral trimethoprim/sulfamethoxazole and moxifloxacin. A whole-body computed tomography did not reveal dissemination to other organs like the lung or brain. The patient was discharged after complete remission. Oral therapy with trimethoprim/sulfamethoxazole, moxifloxacin, rifampicin monthly, clofazimine and thalidomide was prescribed to be taken at home. One month after discharge from the hospital the patient is in good clinical condition with complete resolution of the phlegmon. Conclusion N. farcinica is a rare infectious agent that mainly affects immunocompromised patients. Presentation of phlegmon only without disseminated infection is unusual, even in these kinds of patients. In any case, a higher index of suspicion is needed, as diagnosis can easily be missed due to the absence of characteristic symptoms and the several difficulties usually encountered in identifying the pathogen.