Blood ozonization in patients with mild to moderate COVID-19 pneumonia: a single centre experience.

The emerging outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. We prescribed some promising medication to our patients with mild to moderate pneumonia due to SARS-CoV-2, however such drugs as chloroquine, hydrossichloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab) were not confirmed as effective against SARS-CoV2. We, therefore, started to use auto-hemotherapy treated with an oxygen/ozone (O2/O3) gaseous mixture as adjuvant therapy. In Udine University Hospital (Italy) we performed a case-control study involving hospitalized adult patients with confirmed COVID-19 with mild to moderate pneumonia. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU-Società Italiana di Medicina di Emergenza-Urgenza) and patients that met criteria of phenotypes 2 to 4 were treated with best available therapy (BAT), with or without O3-autohemotherapy. 60 patients were enrolled in the study: 30 patients treated with BAT and O2/O3 mixture, as adjuvant therapy and 30 controls treated with BAT only. In the group treated with O3-autohemotherapy plus BAT, patients were younger but with more severe clinical phenotypes. A decrease of SIMEU clinical phenotypes was observed (2.70 ± 0.67 vs. 2.35 ± 0.88, p = 0.002) in all patients during hospitalization but this clinical improvement was statistically significant only in O3-treated patients (2.87 ± 0.78 vs. 2.27 ± 0.83, p < 0.001), differently to the control group (2.53 ± 0.51 vs. 2.43 ± 0.93, p = 0.522). No adverse events were observed associated with the application of O2/O3 gaseous mixture. O2/O3 therapy as adjuvant therapy could be useful in mild to moderate pneumonia due to SARS-CoV-2. Randomized prospective study is ongoing [Clinical Trials.gov ID: Z7C2CA5837].

Incremental value of FDG-PET/CT to monitor treatment response in infectious spondylodiscitis.

OBJECTIVE: To assess the added value of serial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake analysis in predicting clinical response to treatment in infectious spondylodiscitis (IS). We sought to analyze changes in quantitative FDG-PET/CT parameters among patients with clinical response or treatment failure and to compare the sensitivity and specificity of serial FDG-PET/CT and MRI in predicting treatment response in IS. MATERIALS AND METHODS: This retrospective study consisted of 68 FDG-PET/CT examinations in 34 patients performed before and after at least 2 weeks of antibiotic treatment. Serial MRI scans were available in 32 (94%) patients before and after treatment. FDG-avid lesions were quantified as maximum standardized uptake value (SUVmax), partial-volume corrected lesion metabolic volume (LMV), and partial-volume corrected lesion metabolic activity (LMA). RESULTS: All FDG-PET/CT parameters significantly decreased in patients with clinical improvement (31/34, 91%, P < 0.001), while patients with disease progression did not show FDG-PET/CT improvement. FDG uptake decrease was similar between patients undergoing early assessment (< 6 weeks) compared with those performing FDG-PET/CT after 6 weeks of treatment. SUVmax, LMV, and LMA decrease over time was 39.0%, 97.4%, and 97.1%, respectively. In predicting clinical responses, SUVmax reduction > 15% and > 25% showed 94% and 89% sensitivity and 67% and 100% specificity compared with 37% and 50% of MRI, respectively. Low degree of agreement with clinical response was shown for MRI compared with FDG-PET/CT parameters using the Cohen kappa coefficient. CONCLUSIONS: FDG-PET/CT monitoring is a valuable tool to predict clinical response to treatment in IS and has greater sensitivity and specificity compared with MRI.

Management of vertebral osteomyelitis over an eight-year period: The UDIPROVE (UDIne PROtocol on VErtebral osteomyelitis).

OBJECTIVES: Vertebral osteomyelitis (VO) is a compelling clinical entity for clinicians because of its insidious and indolent course, which makes diagnosis difficult. METHODS: All patients with a suspected diagnosis of VO were analyzed over an 8-year period (January 2009 to January 2017). The UDIPROVE protocol (UDIne PROtocol on VErtebral osteomyelitis) was applied in all cases. The primary endpoint was the performance of the UDIPROVE protocol to obtain the causal bacteria of infection. RESULTS: During the study period, 133 episodes of confirmed VO were observed. The etiology of infection was obtained in 73.6% of cases: 70.5% were gram-positive, 16.3% were gram-negative, and 13.2% were mycobacteria. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed that for tubercular VO, the median standard uptake value (SUV) was higher when compared with VO caused by other bacteria. Clinical cure at the end of therapy was reported in 85.7% of patients. Previous antimicrobial therapy and a delay of more than 5 days in performing biopsy were associated with an undiagnosed etiology of VO. Targeted antibacterial therapy and follow-up with FDG-PET/CT were associated with clinical cure at the end of therapy, while the involvement of more than two vertebrae and inadequate drainage were associated with failure. CONCLUSIONS: Rigorous application of the UDIPROVE protocol allowed the causative pathogens of VO to be obtained - at about twice the rate reported in the literature. The use of FDG-PET/CT for the follow-up of infection was more reliable when compared to magnetic resonance imaging (MRI).

Prosthetic joint infections: clinical management, diagnosis, and treatment.

PURPOSE OF REVIEW: Prosthetic joint infections (PJIs) represent one of the most disastrous complications in prosthetic surgery, requiring long hospitalization, prolonged antimicrobial treatment and repeated surgical interventions. No gold standard test to formulate diagnosis exist. A combination of high index of suspicion, physical examination, microbiological and biohumoral investigations is required. Therapeutical approach should be based on a multidisciplinary team. In our center, a two-stage approach is preferred. As regards the choice of the empirical antibiotic backbone, individual risk factors for multiple-drug resistant (MDR) pathogens should be considered. Several studies enhance the possibility to shorten the length of antibiotic couses. RECENT FINDINGS: Some interesting improvements have been made in the setting of PJIs management. As regards diagnosis, novel biomarkers and nuclear imaging are acquiring more importance. Molecular biology techniques also offer the possibility to formulate rapid microbiological identification. The pattern of PJIs is evolving towards higher rates of MDR causes. During the last decade, a number of new antibiotic molecules with activity against MDRs have been approved. Some of them are also available either in oral formulation or as long-acting compounds, offering the opportunity for early patient's discharge, with expected healthcare costs saving. SUMMARY: Management of PJIs still represents a major threat for clinicians. Improvements in surgical techniques and antibiotic pipeline promise to revolutionize the approach in next years. Despite data from our experience confirm the efficacy of shorter antibiotic courses and the value of new molecules, randomized clinical trials are lacking. More data are needed in order to modify the routine clinical practice.

Post-neurosurgical meningitis: Management of cerebrospinal fluid drainage catheters influences the evolution of infection.

BACKGROUND: In order to better define the pathogenic role of cerebrospinal fluid (CSF) drainage catheters in postoperative patients, we comparatively analyze the clinical course of device and non-device-related meningitis. METHODS: This is an observational, partially prospective, study on consecutive adult patients who developed meningitis after undergoing neurosurgical procedures at the Neurosurgery and Neurointensive care Departments, Spedali Civili, Brescia, Italy, between January 1999 and August 2007. RESULTS: All 77 consecutive post-neurosurgical meningitis events in 65 patients were included in the analysis. Most were classified as external ventricular drainage (EVD)-related meningitis (23 cases, group A), external spinal drainage (ESD)-related meningitis (12 cases, group B), and non-device-related post-neurosurgical meningitis (30 cases, group C). Proven meningitis was identified in 78.3%, 91.7% and 56.7% of the events, respectively. ESD-related meningitis had a shorter onset time vs EVD and non-device-associated meningitis (3 days versus 6 and 7 days, respectively). Median antibiotic treatment duration was 20, 17, and 22.5 days in groups A, B, and C, respectively. Overall, 8 patients (34.8%) in group A, 3 (25.0%) in group B, and 3 (10.0%) in group C died. Median time to become afebrile was shorter in group C than in group A (10 days versus 12 days, P = 0.04). Removal of the device later than 48 hours after meningitis onset, as well as implantation of a second device were associated with a slower time of meningitis resolution. CONCLUSIONS: Early device removal and avoiding implantation of a second device were associated with short illness duration. Larger studies are warranted to confirm the conclusions of this study.

Current antibiotic management of prosthetic joint infections in Italy: the 'Udine strategy'.

The rate of prosthetic joint infections followed and cured at our institution is constantly increasing, in line with epidemiological data from the recent literature. This is probably related to the greater number of knee and hip prostheses implanted every year. For intermediate and late infections, only the two-stage approach is applied, as this demonstrates the best outcome in our experience. Particular attention is paid to microbiological isolation of the pathogen: multiple samples of tissue are collected during the interventions, and kept in culture for a longer period of time than usual. Sonication of prosthetic devices is used to enhance the sensitivity and specificity of the microbiological cultures. Histological examination influences surgical choices either towards implantation of a new prosthesis or replacement of the spacer. An empirical antibiotic backbone of a glycopeptide/lipopeptide and rifampicin is chosen, due to the leading role of Gram-positive bacteria in this setting and the high incidence of methicillin resistance in our centre (>30%), followed by an antibiotic regimen containing linezolid. If specific risk factors are present, an anti-Gram-negative drug is added to the regimen. Duration of therapy depends upon the approach that is chosen, usually being 6 weeks when the prosthesis is removed. Despite at the moment being limited by its small sample size, data from our experience confirms that our empirical approach may represent a valid choice during the early phase of treatment, by keeping linezolid for a step-down therapy of shorter duration (4 weeks).

TDM-guided therapy with daptomycin and meropenem in a morbidly obese, critically ill patient.

OBJECTIVE: To describe a case of severe cellulitis, successfully treated with high-dose daptomycin plus continuous infusion meropenem, in a patient with morbid obesity and renal failure, in whom drug exposure over time was optimized by means of real-time therapeutic drug monitoring (TDM). CASE SUMMARY: A 63-year-old man with morbid obesity (body mass index 81.6 kg/m²) and renal failure was admitted to the emergency department because of severe cellulitis. The patient had an admission Laboratory Risk Indicator for Necrotizing Fasciitis score of 9, and broad-spectrum antimicrobial therapy with daptomycin and meropenem was started. Because of rapidly changing renal function, dosage adjustments were guided by an intensive program of TDM (daptomycin ranging from 1200 mg every 48 hours over 30 minutes to 1200 mg every 36 hours over 30 minutes; meropenem ranging from 0.25 g every 8 hours over 6 hours to 500 mg every 4 hours by continuous infusion). Clinical response was observed within 72 hours. However, a sudden increase of serum creatine kinase (SCK) raised questions about the need for discontinuation of daptomycin. The drug concentrations were not toxic; therefore, we decided to continue therapy. Significant clinical improvement, with SCK normalization, was observed within a few days. Antimicrobial therapy was switched on day 29 to amoxicillin/clavulanate plus levofloxacin, and then discontinued at discharge on day 53. DISCUSSION: High-dose daptomycin plus continuous infusion meropenem may ensure adequate empiric antimicrobial coverage in patients with possible early necrotizing fasciitis. However, in patients with morbid obesity and changing renal function, significant challenges may arise because of the hydrophilic nature of these drugs and the inaccuracy of standard methods of estimating renal function. CONCLUSIONS: Real-time TDM may represent an invaluable approach in optimizing drug exposure with high-dose daptomycin plus continuous infusion meropenem in patients with severe cellulitis, morbid obesity, and changing renal function.

Haemostatic activation in HIV infected patients treated with different antiretroviral regimens.

HIV infected patients treated with highly active antiretroviral therapy (HAART) may be at increased risk of cardiovascular events, particularly if based upon the use of protease inhibitors (PI). We investigated the haemostatic markers of cardiovascular risk in 115 HIV infected subjects, divided into four groups : 1) patients naïve to antiretroviral therapy (Naïve; n=34 patients), or subjects that had been on a stable combination therapy for > or =12 months with either: 2) double reverse transcriptase nucleoside analogue inhibitors therapy (2NRTI; n=26), 3) 2NRTI backbone plus a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI; n=27), and 4) on a PI based regimen (PI; n=28). Forty-four healthy subjects were included as controls. Naïve as well as 2NRTI and NNRTI differed from controls for higher F1+2 (P<.0001) and FVII (P<.007) levels. When comparing PI patients with controls we observed significantly higher levels of Fbg (P=.035), FVII (P<.0001), TM (P<.0089), vWF (P=.009), and F1+2 (P<.0001). The only difference observed among the 4 groups of HIV infected patients was a significantly lower level of F1+2 in PI as compared with NNRTI patients (P=.05) At least one abnormal result was observed in > or = 90.6% of HIV infects groups, vs 43.2% of controls (P<.0001 in all cases). In conclusion, a) HIV infection per se may alter the haemostatic markers of cardiovascular risk, b) minor differences were observed among the different classes of HIV infected patients, namely between NNRTI and PI treated patients.

Major role of levofloxacin in the treatment of a case of Listeria monocytogenes meningitis.

We report a case of acute bacterial meningitis due to Listeria monocytogenes whose successful treatment was mainly attributable to high-dose levofloxacin therapy (500 mg iv bid). This supports the hypothesis that levofloxacin may be an effective option for the treatment of listerial meningitis.