Exosomal miR-17-5p, miR-146a-3p, and miR-223-3p Correlate with Radiologic Sequelae in Survivors of COVID-19-Related Acute Respiratory Distress Syndrome.

We investigated the association between circulating microRNAs (miRNAs) potentially involved in the lung inflammatory process and fibrosis development among COVID-19-related acute respiratory distress syndrome (ARDS) survivors. At 4 ± 2 months from clinical recovery, COVID-19-related ARDS survivors matched for age, sex, and clinical characteristics underwent chest high-resolution computerized tomography (HRCT) and were selected based on imaging pattern evolution into fully recovered (N = normal), pulmonary opacities (PO) and fibrosis-like lesions (FL). Based on the previous literature, we performed plasma miRNA profiling of exosomal miRNAs belonging to the NLRP3-inflammasome platform with validated (miR-17-5p, miR-223-3p) and putative targets (miR-146a-5p), miRNAs involved in the post-transcriptional regulation of acute phase cytokines (miR128-3p, miR3168, miR125b-2-3p, miR106a-5p), miRNAs belonging to the NLRP4-inflammasome platform (miR-141-3p) and miRNAs related to post-transcriptional regulation of the fibrosis process (miR-21-5p). miR-17-5p, miR-223-3p, and miR-146a-5p were significantly down-regulated in patients with FL when compared to patients with PO. miR-146a-5p was also down-regulated in patients with FL than in N. The expression of the remaining miRNAs did not differ by group. In patients with long-term pulmonary radiological sequelae following COVID-19-related ARDS, a down-regulation of miR-17-5p, miR-146a-3p, and miR-223-3p correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. Our results support the hypothesis that NLRP3-Inflammasome could be implicated in the process of fibrotic evolution of COVID-19-associated ARDS.

Synergistic Activity of Remdesivir-Nirmatrelvir Combination on a SARS-CoV-2 In Vitro Model and a Case Report.

BACKGROUND: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. METHODS: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. RESULTS: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h, with an HSA score of 52.8 and 28.6, respectively (p < 0.0001). These data were confirmed by performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir until she tested negative. CONCLUSIONS: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

Prosthetic joint infection diagnosis applying the three-level European Bone and Joint Infection Society (EBJIS) approach.

Sensitive and specific tests for the diagnosis of prosthetic joint infection (PJI) are lacking. The aim of this study was to report clinical and microbiological findings of consecutive patients diagnosed with PJI at the University Hospital of Perugia, Perugia, Italy, and to validate these diagnoses utilizing the European Bone and Joint Infection Society (EBJIS) three-level diagnostic approach from 2021. Patients with a PJI diagnosis were included in this study and examined retrospectively. Overall, 133 patients were diagnosed with PJI: mean age 72 years, 54.9% female, and 55.6% with more than one comorbidity. The most frequent involved joints were hip 47% and knee 42%. Aetiology was identified in 88/133 (66.2%): staphylococci resulted the most frequent microorganisms and over 80% (45/54) resulted rifampin susceptible. Applying the EBJIS approach, PJI diagnosis resulted: confirmed in 101 (75.9%), likely in 25 (18.8%), and unlikely in 7 (5.3%). Likely PJIs aetiology was Staphylococcus aureus 11/25, coagulase-negative staphylococci 8/25, Streptococcus agalactiae 3/25, viridans group streptococci 2/25, and Pseudomonas aeruginosa 1/25. No statistically significant differences were detected among the three diagnosis groups with regard to clinical characteristics with the exception of a higher number of confirmed PJIs occurring < 3 months after implantation. The logistic regression analysis did not disclose any independent predictor of confirmed PJIs. We recommend using all the diagnostic tests available to approach PJI diagnosis, and suggest caution before rejecting PJI diagnosis in the presence of highly virulent microorganisms from a single sample, in patients without sinus tract, and in those receiving antimicrobial at the time microbiologic samples are collected. Study approved by Umbrian Regional Ethical Committee, Perugia, Italy, Prot. N. 23,124/21/ON of 10.27.2021.

A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study.

OBJECTIVES: Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies have shown that a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon-γ-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. METHODS: This prospective, multicentre cohort study, entitled AutoPilot-Dx, aimed to validate signature performance and to estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data. RESULTS: In total, 1140 patients were recruited (February 2017-December 2018), of which 1008 met the eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with a sensitivity of 93.7% (95%CI 88.7-98.7), a specificity of 94.2% (92.2-96.1), positive predictive value of 73.0% (65.0-81.0), and negative predictive value of 98.9% (98.0-99.8); in 9.8% the test results were equivocal. The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients. CONCLUSIONS: The findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections.

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study.

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients ( n = 57 ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( n = 16 ), Pseudomonas aeruginosa ( n = 14 ; XDR 50 %), Klebsiella spp. ( n = 7 ), Enterobacter spp. ( n = 9 ), Acinetobacter spp. ( n = 5 ), Proteus mirabilis ( n = 3 ), Serratia marcescens ( n = 2 ) and Stenotrophomonas maltophilia ( n = 1 ). The prevalence of ESBL (extended-spectrum ß -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( n = 37 ; 64.9 %) were treated with a combination including carbapenems ( n = 32 ) and colistin ( n = 11 ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( p = 0.008 ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age > 60  years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; p = 0.004 ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; p = 0.024 ). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

QuantiFERON-TB and tuberculin skin test in patients with active tuberculosis: the experience of a single medium-sized Italian University Hospital.

Interferon-γ releasing assays (IGRAs) are currently widely employed in the initial work up of Mycobacterium tuberculosis infection, as well as in suspected tuberculosis (TB). These assays are commonly utilized over the Tuberculin Skin Test (TST) in high resource and low TB burden settings, despite the unclear benefits shown in such contexts. The debate on the use of TST and IGRAs is of current interest also in Italy due to the increasing presence of immigrants from countries with a high incidence of TB and the rising attention of health care institutions to economic costs. The aim of this study was to compare QuantiFERON-TB (QFT) and TST results in active TB. We evaluated QFT results and TST reactions from 245 consecutive patients having both tests, registered among 411 patients admitted for TB at the Infectious Disease Clinic, Department of Medicine of the University of Perugia (Italy). We compared the rates of positive QFT and TST tests and noted no statistically significant differences overall or in relation to age, gender, HIV status and TB localization. Among foreign-born patients with confirmed TB, we observed a lower rate of positive TST results. The results of our study indicated that both QFT and TST can be used in the work up of TB having special attention when evaluating foreign-born patients.

Daptomycin-based aminoglycoside-sparing therapy for streptococcal endocarditis: a retrospective multicenter study.

Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy. Retrospective, multicenter, observational study. All patients with streptococcal IE admitted from 2016 to 2018 were enrolled. Mortality and incidence of acute kidney injury (AKI) were compared between Group A (standard of care, SoC) and Group B (daptomycin-based aminoglycoside-sparing combination therapy). Fifty-four patients were enrolled, 33 in Group A and 21 in Group B. Mortality was 2/33 (6%) in Group A and 0 in Group B (p = 0.681); AKI incidence was 8/33 (24%) in Group A and 0 in Group B (p = 0.04). Daptomycin-based aminoglycoside-sparing combination therapy appears to be promising for the treatment of streptococcal endocarditis because of similar efficacy compared with SoC and significantly reduced incidence of AKI.

In vitro antibacterial activity of ceftazidime/avibactam in combination against planktonic and biofilm carbapenemase-producing Klebsiella pneumoniae isolated from blood.

OBJECTIVES: The aim of this study was to report on in vitro tests of antibacterial activity of ceftazidime/avibactam in combination against planktonic or biofilm KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), the rate of KPC-Kp blood isolates in University of Perugia Hospital over a 5-year period, and their antimicrobial susceptibility patterns. METHODS: The antibacterial activity of ceftazidime/avibactam in combination with other antimicrobials was assessed against planktonic and biofilm bacteria by Etest and checkerboard assay. A retrospective review of laboratory data was performed to evaluate the rate of KPC-Kp from blood samples and their antimicrobial susceptibility patterns. RESULTS: Between 2014 and 2019, 130/4241 (3.1%) KPC-Kp were identified from blood cultures. Their rate increased from 2.3% in 2014-2015 to 4.5% over the last 3 years. Overall, 4.6% (6/130) of KPC-Kp isolates were susceptible to meropenem, 65.4% (85/130) to colistin, 65.1% (84/129) to tigecycline, 34.6% (45/130) to amikacin, 36.2% (42/116) to gentamicin, 40.2% (39/97) to fosfomycin and 91.5% (65/71) to ceftazidime/avibactam. Five of six ceftazidime/avibactam-resistant KPC-Kp were isolated from patients not treated with ceftazidime/avibactam. Synergism was detected both by Etest and checkerboard assay for the combination of ceftazidime/avibactam plus meropenem against planktonic isolates, whilst lower bactericidal activity was observed in biofilm KPC-Kp isolates. CONCLUSIONS: Our in vitro data suggest that the combination of ceftazidime/avibactam plus meropenem has a synergistic antibacterial activity against planktonic bacteria, whilst a lower activity was detected against biofilm, suggesting worse clinical outcomes whenever biofilm infections are present. Further analyses are required to confirm these results before extending them to clinical practice.

Improving the etiological diagnosis of osteoarticular infections with the commercial multiplex real-time polymerase chain reaction SeptiFast®.

Detection of etiological agents is pivotal for adequate therapy of osteoarticular bacterial infections. Culture often lacks sensitivity, especially in patients under antibiotic therapy. The present study investigates the potential clinical utility of the commercial multiplex real-time polymerase chain reaction SeptiFast® (SF) in the etiological diagnosis of osteoarticular infections. Results obtained from conventional culture and SF were compared in 86 osteoarticular specimens collected from patients with suspected infection. The number of specimens positive by SF (38/86, 44.18%) was significantly greater (P = 0.001) than that of specimens positive by culture (20/86, 23.25%). The sensitivity of SF was 48.71%, significantly higher than culture sensitivity (25.64%). Specificity was 100% for both tests. The overall diagnostic accuracy for SF was 53.48%, and that of culture was 32.55%. Even with the limitation of the low number of specimens, this study supports the usefulness of SF in the diagnosis of osteoarticular infections.

Procalcitonin, white blood cell count and C-reactive protein as predictors of S. aureus infection and mortality in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell - WBC - count, C-reactive protein - CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. METHODS: Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. RESULTS: Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers < cut-offs. AUC values for in-hospital death were 0.702, 0.725 and 0.727 for the WBC, CRP, and procalcitonin, respectively. Among inflammatory biomarkers, WBC and procalcitonin independently predicted in-hospital death. Procalcitonin refined risk stratification when added to WBC, and to the combination of WBC and CRP. Patients with WBC ≥ 10,535/mm3, CRP ≥ 85 mg/dL, and procalcitonin ≥ 0.4 ng/mL had a 27-fold higher risk of in-hospital death than patients with all biomarkers < cut-offs. CONCLUSIONS: Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

An Italian Case of Disseminated Histoplasmosis Associated with HIV.

Histoplasma capsulatum is a dimorphic fungus, endemic in the Americas, Africa (var. duboisii), India, and Southeast Asia. H. capsulatum infection is rarely diagnosed in Italy, while in Latin America, progressive disseminated histoplasmosis (PDH) is one of the most frequent AIDS-defining illnesses and causes of AIDS-related deaths. We report a case of PDH and new HIV infection diagnosis in a Cuban patient, who has been living in Italy for the past 10 years. Bone marrow aspirate and peripheral blood smear microscopy suggested H. capsulatum infection. The diagnosis was confirmed with the culture method identifying its thermal dimorphism. Liposomal amphotericin B was administered alone for 10 days and then for another 2 days, accompanied with voriconazole; the former was stopped for probable side effects (persistent fever and worsening thrombocytopenia), and voriconazole was continued to complete 4 weeks. PDH maintenance treatment consisted of itraconazole for one year. Antiretroviral therapy (ART) was started on the third week of antifungal treatment. At the 3-year follow-up, the patient is adherent on ART, the virus was suppressed, and she has an optimal immune recovery. This case highlights the need to suspect histoplasmosis in the differential diagnosis of opportunistic infections in immunocompromised persons, native to or who have traveled to endemic countries.

Two-stage revision and systemic antifungal therapy of Candida glabrata primary prosthetic hip infection successfully treated: a case report.

BACKGROUND: Overall, fungi are estimated to cause approximately 1% of prosthetic joint infections, Candida glabrata account for less than 10% of these cases. No well-defined treatment strategy is available. CASE PRESENTATION: A 71-year-old Caucasian man with non-insulin-dependent diabetes was admitted for hip prosthesis revision. For the past 17 years he suffered from recurrent infection of a perianal fistula, the last episode being 1 week before admission, and was prescribed amoxicillin/clavulanate 1 g twice a day. At surgery, the synovial fluid tested positive for infection with the Synovasure® Alpha Defensin Test, and the orthopedic surgeon reported intraoperative evidence of infection. While the synovial fluid failed to grow microorganisms, seven different samples including periprosthetic tissue and the prosthesis grew Candida glabrata. Imipenem 2 g and teicoplanin 600 mg daily were administered during surgery. Also an antibiotic loaded spacer was positioned. A week later micafungin 100 mg a day was added, and after another week imipenem was replaced with ertapenem 1 g once a day. The combination of antibiotics and antifungal was administered for a total of 7 weeks, while he also underwent treatment of the perianal fistula. The reimplantation was performed after an 8-week antibiotic-free interval. Before reimplantation, his erythrocyte sedimentation rate and C-reactive protein level were normal. At reimplant surgery, several samples were collected for microbiology, before administering ertapenem 1 g, teicoplanin 600 mg and micafungin 100 mg once a day. This antimicrobial combination was continued for 15 days until the microbiologic investigations, including culture and molecular testing after sonication technique of the spacer, were reported negative for bacteria and fungi. In this patient, systemic antifungal and extensive debridement allowed for clinical and microbiologic cure. CONCLUSIONS: Although Candida glabrata prosthetic joint infection is a rare event, the incidence could increase in the future, and there is need for more definitive treatment protocols. Diagnosis depends on culture. Fungal etiology must always be included in the differential diagnosis of prosthetic joint infection.

Measurement and prediction of antimicrobial resistance in bloodstream infections by ESKAPE pathogens and Escherichia coli.

OBJECTIVES: This study aimed to evaluate a cumulative antimicrobial resistance index (ARI) as a possible key outcome measure of antimicrobial stewardship programmes (ASPs) and a tool to predict the antimicrobial resistance (AMR) trend. METHODS: Antimicrobial susceptibility for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli (ESKAPEEc) pathogens recovered from blood cultures during a 5-year period (2014-2018) was analysed to obtain a cumulative ARI. For each antibiotic tested, a score of 0, 0.5 or 1 was assigned for susceptibility, intermediate resistance or resistance, respectively, and the ARI was calculated by dividing the sum of these scores by the number of antibiotics tested. Cumulative ARIs of ESKAPEEc micro-organisms were compared and a mathematical prediction model for AMR trend was obtained. RESULTS: In total, 1858 ESKAPEEc isolates were included in the study. The cumulative ESKAPEEc mean ARI increased significantly from 0.200 ± 0.01 in 2014 to 0.276 ± 0.02 in 2018 (P < 0.001). In multivariable regression analysis, factors significantly associated with ARI ≥ 0.5 were E. faecium, K. pneumoniae, P. aeruginosa and A. baumannii infection (P < 0.001) and infection occurring after 2014 (P < 0.05). Based on the prediction model obtained, in the absence of any interventional measure, a tendency to pandrug resistance of the ESKAPEEc group could be expected in the next 8-15 years. CONCLUSION: The ARI could be a useful tool to measure the impact of ASPs on AMR. The increasing incidence of AMR among ESKAPEEc organisms underscores the needing for ASPs.

Meningitis with cranial polyneuritis and cavernous sinus thrombosis by Borrelia crocidurae: First autochthonous case in Europe.

Borrelia crocidurae is endemic in West Africa, where it represents the leading cause of tick-borne relapsing fever (TBRF). TBRF typically presents with high fever and systemic symptoms, followed by recurrent episodes. Neurological complications may occur during febrile relapses. B. crocidurae is considered the most neurotropic agent of TBRF and is associated to severe neurological manifestations i.e. meningitis and encephalitis. To date, European cases of B. crocidurae infection have been reported in travelers returning from endemic areas. We report the first autochthonous case in Europe of B. crocidurae infection, presenting as meningitis with cranial polyneuritis and cavernous sinus thrombosis that were not preceded by classic febrile recurrences.

Treating Primary Arthroprosthesis Infection Caused by Mycobacterium abscessus subsp. abscessus.

Prosthetic joint infections (PJI) caused by nontuberculous mycobacteria are very rare, and results of treatment can be unpredictable. A 72-year-old female underwent hip replacement after an accidental fall in a local hospital in Santo Domingo. The postoperative period was uneventful except for a traumatic wound near the surgical scar. PJI caused by Mycobacterium abscessus subsp. abscessus was diagnosed 6 months later. A two-stage reimplantation was performed after a 3-month period of aetiology-directed therapy, including amikacin, imipenem, and clarithromycin. M. abscessus isolate was reported to be resistant to clarithromycin when incubation was protracted for 14 days and to harbour the gene erm(41). The patient manifested major side effects to tigecycline. At reimplant, microbiologic investigations resulted negative. Overall, medical treatment was continued for a 7-month period. When discontinued and at 6-month follow-up, the patient was clinically well, inflammatory markers were normal, and the radiography showed well-positioned prosthesis. Mycobacterium abscessus subsp. abscessus is a very rare cause of PJI, yet it must be included in the differential diagnosis, especially when routine bacteria cultures are reported being negative. Further investigations are needed to determine any correlations between clinical results and in vitro susceptibility tests, as well as the clinical implications of M. abscessus subsp. abscessus harbouring the functional gene erm(41). Moreover, investigations are needed for determine optimal timings of surgery and lengths of medical therapy to improve patient outcome.

Multidrug-resistant and extensively drug-resistant Gram-negative prosthetic joint infections: Role of surgery and impact of colistin administration.

Factors influencing treatment outcome of patients with Gram-negative bacterial (GNB) multidrug-resistant (MDR) and extensively drug-resistant (XDR) prosthetic joint infection (PJIs) were analysed. Data were collected (2000-2015) by 18 centres. Treatment success was analysed by surgery type for PJI, resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) using logistic regression and survival analyses. A total of 131 patients (mean age 73.0 years, 35.9% male, 58.8% with co-morbidities) with MDR (n = 108) or XDR (n = 23) GNB PJI were assessed. The most common pathogens were Escherichia coli (33.6%), Pseudomonas aeruginosa (25.2%), Klebsiella pneumoniae (21.4%) and Enterobacter cloacae (17.6%). Pseudomonas aeruginosa predominated in XDR cases. Isolates were carbapenem-resistant (n = 12), fluoroquinolone-resistant (n = 63) and ESBL-producers (n = 94). Treatment outcome was worse in XDR versus MDR cases (P = 0.018). Success rates did not differ for colistin versus non-colistin in XDR cases (P = 0.657), but colistin was less successful in MDR cases (P = 0.018). Debridement, antibiotics and implant retention (DAIR) (n = 67) was associated with higher failure rates versus non-DAIR (n = 64) (OR = 3.57, 95% CI 1.68-7.58; P < 0.001). Superiority of non-DAIR was confirmed by Kaplan-Meir analysis (HR = 0.36, 95% CI 0.20-0.67) and remained unchangeable by time of infection (early/late), antimicrobial resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) (Breslow-Day, P = 0.737). DAIR is associated with higher failure rates even in early MDR/XDR GNB PJIs versus implant removal. Colistin should be preserved for XDR cases as it is detrimental in MDR infections.

Effect of aspirin treatment on abacavir-associated platelet hyperreactivity in HIV-infected patients.

BACKGROUND: Ischemic cardiovascular events are a relevant cause of morbidity and mortality in HIV-infected patients. Use of abacavir (ABC), a nucleoside analog reverse transcriptase inhibitor, has been associated with increased risk of myocardial infarction (MI) and with platelet hyperreactivity. We explored whether low-dose aspirin reduces in vivo platelet activation and platelet hyperreactivity induced by ABC in HIV-infected subjects. METHODS AND RESULTS: In a randomized, placebo-controlled, cross-over study forty HIV-infected patients with ABC-associated platelet hyperreactivity, defined by a score based on laboratory variables reflecting in vivo platelet activation and ex vivo platelet hyperresponsiveness, were randomized to aspirin 100 mg daily for 15 days with subsequent cross-over to placebo for additional 15 days or placebo for 15 days with subsequent cross-over to aspirin for further 15 days. In vivo and ex vivo platelet activation markers were measured at day 15 and 30. One group of healthy subjects, one of untreated HIV infected-patients and one treated without ABC, were studied concomitantly. Serum TxB2 and urinary 11-dehydro-TxB2 were decreased by aspirin in ABC-treated patients, but not as much as in healthy controls. Aspirin therapy reduced significantly platelet hyperreactivity (score: from 9.3, 95% CIs 8.7 to 10.0, to 7.5, 6.9 to 8.0), however without bringing it back to the levels of healthy controls (score: 4.6, 95% CIs 3.6 to 5.6). CONCLUSION: Aspirin reduces ABC-induced in vivo platelet activation and platelet hyperreactivity in HIV-infected patients, however without normalizing them. Whether the observed reduction of platelet activation is sufficient to prevent cardiovascular events requires a prospective trial.

Non-primary nail-plate syphilis in an HIV-infected patient.

A 37-year-old Caucasian male, HIV-infected (CDC A2) in 2012 and on antiretroviral therapy, presented for a follow-up visit. On physical examination, a barely discernible light-colored macular rash was observed on the trunk, not involving the palms and soles. However, clear maculo-papular lesions were present over the proximal volar aspect of both forearms. Furthermore, well-demarked purplish, opaque, rough, vertically ridged plaque-like lesions were observed over the proximal portions of fingernails. The patient reported that cutaneous and nail lesions had appeared about 2 months prior and that he had engaged in unprotected sex 5 months before. Serologic tests for syphilis resulted reactive. Intramuscular injection of benzathine penicillin G, 2.4 million units, was administered once a week for 3 weeks. One month after therapy, the rash was no longer present, and at 5 months, nail abnormalities had disappeared. The clinical findings, the serologic results, and the disappearance of skin and nail lesions after the administration of penicillin strongly suggest that this HIV-infected patient had secondary or early late syphilis with skin and nail-plate involvement. We are experiencing a resurgence of syphilis as well as an increase in unusual and/or forgotten clinical manifestations. Syphilis remains a diagnostically challenging disease.