SARS-CoV-2 Variants in COVID-19 Disease: A Focus on Disease Severity and Vaccine Immunity in Patients Admitted to the Emergency Department.

Tracking SARS-CoV-2 variants along with vaccinations are fundamental for severe COVID-19 disease prevention. A study was performed that focused on 43 patients with the SARS-CoV-2 infection who were admitted to the Emergency Department. RT-PCR-positive nasopharyngeal samples were sequenced using the MiSeq II system for variant detection. The main reason for Emergency Department admission was COVID-19 (67%), followed by other causes (33%); 51% patients were unvaccinated or vaccinated with a single dose and 49% had completed the vaccination course with two or three doses. Among the vaccinated group, 38% were admitted for COVID-19, versus 94.5% of the unvaccinated group. After admission, 50% of the vaccinated group and 36% of the unvaccinated group were discharged and allowed to go home, and 80% of the unvaccinated had no major comorbidities; 63% needed hospital admission and 5% required a stay in the Intensive Care Unit. Of these, 37% were vaccinated with 3 doses, 11% with two doses, 4% with a single dose, and 48% were unvaccinated. The 70% of the vaccinated patients who were admitted to hospital presented major comorbidities versus 38% of the unvaccinated group. Two unvaccinated patients that needed intensive care had relevant comorbidities and died. Genome sequencing showed the circulation of three omicron and two pure sub-lineages of omicron, including 22 BA.1, 12 BA.1.1, and 7 BA.2. Data showed the SARS-CoV-2 national and international migration patterns and how vaccination was useful for severe COVID-19 disease prevention.

Genomic Epidemiology Unveil the Omicron Transmission Dynamics in Rome, Italy.

Since 2020, the COVID-19 pandemic represented an important worldwide burden. Well-structured surveillance by reliable and timely genomic data collection is crucial. In this study, a genomic monitoring analysis of all SARS-CoV-2 positive samples retrieved at the Fondazione Policlinico Universitario Campus Bio-Medico, in Rome, Italy, between December 2021 and June 2022, was performed. Two hundred and seventy-four SARS-CoV-2-positive samples were submitted to viral genomic sequencing by Illumina MiSeqII. Consensus sequences were generated by de novo assembling using the iVar tool and deposited on the GISAID database. Lineage assignment was performed using the Pangolin lineage classification. Sequences were aligned using ViralMSA and maximum-likelihood phylogenetic analysis was performed by IQ-TREE2. TreeTime tool was used to obtain dated trees. Our genomic monitoring revealed that starting from December 2021, all Omicron sub-lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) were circulating, although BA.1 was still the one with the highest prevalence thought time in this early period. Phylogeny revealed that Omicron isolates were scattered throughout the trees, suggesting multiple independent viral introductions following national and international human mobility. This data represents a sort of thermometer of what happened from July 2021 to June 2022 in Italy. Genomic monitoring of the circulating variants should be encouraged considering that SARS-CoV-2 variants or sub-variants emerged stochastically and unexpectedly.

SARS-CoV-2 AY.4.2 variant circulating in Italy: Genomic preliminary insight.

The appearance of emerging variants of SARS-CoV-2 carrying mutations into the spike protein has recently raised concern with respect to tracking their transmission and mitigating the impact in the evolving pandemic across countries. AY.4.2, a recently detected Delta variant sublineage, is considered a new variant under investigation (VUI) as it carries specific genetic signatures present in the spike protein, called Y145H and A222V. Here, using genomic epidemiology, we provide the first preliminary insight regarding the circulation of this emerging VUI in Italy.

Genetic diversity of Staphylococcus aureus influences disease phenotype of systemic lupus erythematosus.

OBJECTIVE: We investigated the genetic diversity, molecular epidemiology and evolutionary dynamics of Staphylococcus aureus (SA) isolated from SLE patients by means of phylogenetic analysis. METHODS: Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of the translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate relationships and to assess significant clades. Selective pressure analysis was used to investigate the evolution of the SA tuf gene. The gene sequences from non-SLE individuals, downloaded from the GenBank database, were compared through phylogenetic analysis with the tuf gene from SLE patients. RESULTS: We enrolled 118 patients [M/F 10/108; median (interquartile range (IQR)) age 45.5 (13.2) years; median (IQR) disease duration 120 (144) months]. Twenty-four patients (20.3%) were SA carriers (SA+), three of them MRSA. SA+ SLE showed significantly higher SLEDAI-2k values [SA+: median (IQR) 2 (3.75); SA-: 0 (2); P = 0.04]. The phylogenetic analysis, restricted to 21 non-MRSA SA+, revealed a statistically supported larger clade (A, n = 17) and a smaller one (B, n = 4). Patients located in clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P < 0.0001) and SA- (62.7%, P < 0.0001). Haematological manifestations were significantly more frequent in clade A (64.7%) compared with B (50.0%, P = 0.004). CONCLUSION: We suggest a possible role of SA nasal carriage status in SLE disease activity. Moreover, our findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.

Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU.

Early diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991, Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM). In this prospective study, 209 consecutive patients with clinical diagnosis of sepsis were enrolled (May 2014-June 2018) outside intensive care unit (ICU) setting. A diagnostic protocol could include SIRS criteria or qSOFA score evaluation, rapid testing of PCT and MR-proADM, and SOFA score calculation for organ failure definition. Using this approach outside the ICU, a rapid diagnostic and prognostic evaluation could be achieved, also in the case of negative SIRS, qSOFA or SOFA scores with high post-test probability to reduce mortality and improve outcomes.

Migrants rescued on the Mediterranean Sea route: nutritional, psychological status and infectious disease control.

INTRODUCTION: North Africa has become a key migratory hub where a large number of migrants attempt the journey by sea from the Libyan coastline to the south of Europe. In this humanitarian disaster scenario, the Mediterranean route has been one of the most used by illegal boats. METHODOLOGY: In this report, the state of physical and psychological health of a cluster of Eritrean migrants, escaped from Libya and rescued in the Mediterranean Sea after a shipwreck, was described by epidemiological, clinical and laboratory investigations. RESULTS: Data suggest that despite the majority  of the migrants being apparently in good health upon a syndromic surveillance approach, most of them suffered a decline in psychological status as well as severe malnutrition. The emergence of infectious diseases, related to poor living conditions during the journey, is not a rare event. CONCLUSION: The present report highlights the risks of failures of the syndromic medical approach in the setting of the extremely challenging migration route and underlines migrant frailties consequent to a prolonged journey and long period of detention. These stressors, which can degrade the initial health condition of traveling migrants, can lead to a premature "exhausted migrant effect" that should be carefully investigated in order to avoid the early emergence of diseases related to frailty.

Procalcitonin and MR-proAdrenomedullin combination in the etiological diagnosis and prognosis of sepsis and septic shock.

Procalcitonin and Mid-regional pro Adrenomedullin have been proposed for sepsis diagnosis, antibiotic therapy guidance and prognosis. A retrospective analysis of PCT and MR-proADM on 571 consecutive patients with sepsis diagnosis was performed. Median values were compared using the non-parametric Mann-Whitney's test. Receiver operating characteristic analysis was performed to define cutoff points for sepsis diagnosis. Pretest odds, posttest odds, and posttest probability have been calculated. Data were analyzed using Med-Calc 11.6.1.0 software. PCT resulted excellent in gram-negative, but less performant in gram-positive and fungal etiologies. MR-proADM values resulted homogenously distributed within the different microbial classes and increased significantly in septic shock. PCT highest PPV value was found to distinguish gram-negative from fungal sepsis and septic shock (>3. 57 ng/mL, PPV 0.96 and > 8.77 ng/mL, PPV 0.96, respectively). Good diagnostic accuracy was evidenced to discriminate gram-negative from gram-positive septic shock (>3.88 ng/mL PPV 0.89). Lower diagnostic accuracy was evidenced to discriminate gram-negative and gram-positive sepsis (>0.80 ng/mL, PPV 0.78) and gram-positive from fungal septic shock (>1.74 ng/mL PPV 0.75). The lowest PCT PPV (0.28) was found in gram-positive and fungal sepsis distinction. MR-proADM discriminating cut-offs were homogeneously distributed in Gram-negative and Gram-positive sepsis and were higher in septic shock, but not influenced by pathogen etiologies. MR-proADM cut-off values > 3.39 nmol/L in sepsis and >4.33 nmol/L in septic shock were associated with significant higher risk of 90-days mortality. In conclusion, PCT and MR-proADM combination represents an advantage for sepsis diagnosis and for 90-days mortality risk stratification.

Phylogenetic Analysis of Multi-Drug Resistant Klebsiella pneumoniae Strains From Duodenoscope Biofilm: Microbiological Surveillance and Reprocessing Improvements for Infection Prevention.

Duodenoscopes have been described as potential vehicles of patient-to-patient transmission of multi-drug resistant organisms. Carbapenem-resistant Enterobacteriaceae duodenoscope related infections have been described by the Center for Disease Control and the US Food and Drug Administration consequently to outbreaks occurring in the United States. These evidences suggested that improved microbiological surveillance and endoscope design optimization could represent valid tools to improve infection control. At this aim, in this study an example of duodenoscope microbiological surveillance and reprocessing improvement analyzing strains component of bacterial biofilm by phylogenetic analysis has been proposed. From September 2016 to December 2017, duodenoscope instruments were subjected to microbial surveillance by post-reprocessing cultures of liquid collected by internal channels of instruments after injection and aspiration cycles and membrane filtration. During surveillance seventeen Klebsiella pneumoniae, of which 10/17 (58.8%) MDR and KPC strains were collected from duodenoscope instruments plus one MDR Klebsiella pneumoniae strain from the rectal swab performed before ERCP procedure in an inpatient. The surveillance allowed evidencing potential failure of reprocessing procedure and performing consequent reprocessing improvements including the contaminated instruments quarantine until their negativity. Phylogenetic analysis of whole genome sequence of duodenoscope strains plus inpatients MDR strains, showed intermixing between duodenoscopes and inpatients, as evidenced by minimum spanning tree and time-scale Maximum Clade Credibility tree. In minimum spanning tree, three groups have been evidenced. Group I including Klebsiella pneumoniae strains, isolated from inpatients before microbiological surveillance adoption; group II including intermixed Klebsiella pneumoniae strains isolated from inpatients and Klebsiella pneumoniae strains isolated from duedonoscopes and group III including Klebsiella pneumoniae strains exclusively from duedonoscope instruments. In the Maximum Credibility Tree, a statistically supported cluster including two Klebsiella pneumoniae strains from duedonoscope instruments and one strains isolated from an inpatient was showed. From the first microbiologic surveillance performed on September 2016 and after the reprocessing improvement adoption, none MDR or susceptible Klebsiella pneumoniae strain was isolated in the following surveillance periods. In conclusion, these results should encourage hospital board to perform microbiological surveillance of duodenoscopes as well as of patients, by rectal swabs culture, and rapid molecular testing for antimicrobial resistance before any endoscopic invasive procedure.

The transmission dynamic of Madariaga Virus by bayesian phylogenetic analysis: Molecular surveillance of an emergent pathogen.

Madariaga Virus (MADV) is an emergent Alphavirus of the eastern equine encephalitis virus (EEEV) strain complex causing epizootic epidemics. In this study the genetic diversity and the transmission dynamics of Madariaga virus has been investigated by Bayesian phylogenetics and phylodynamic analysis. A database of 32 sequences of MADV group structural polyprotein were downloaded from GenBank, aligned manually edited by Bioedit Software. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Neighbor-joining tree was generated using MEGA7. The phylogenetic signal of the dataset was tested by the likelihood mapping analysis. The Bayesian phylogenetic tree was built using BEAST. Selective pressure analysis revealed one positive selection site. The phylogenetic trees showed two main clusters. In particular, Lineage II showed an epizootic infection in monkeys and Lineage III, including 2 main clusters (IIIa and IIIB), revealing an epizootic infection in humans in Haiti and an epizootic infection in humans in Venezuela during the 2016, respectively. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor estimates, showed that the root of the tree dated back to the year 346 with the probable origin in Brazil. Gene flow analysis revealed viral exchanges between different neighbor countries of South America. In conclusion, Bayesian phylogenetic and phylodynamic represent useful tools to follow the transmission dynamic of emergent pathogens to prevent new epidemics spreading worldwide.

MALDI-TOF MS Identification and Clustering Applied to Enterobacter Species in Nosocomial Setting.

Enterobacter microorganisms cause important bacterial infections in humans. Recently, carbapenem resistant isolates carrying the blaKPC gene were described and their clonal transmission in different nosocomial outbreaks reported. In this study, the relative numbers of Enterobacter species, their antimicrobial susceptibility along 3 years of observation and the identification ability of the two most common MALDI-TOF platforms were evaluated. A clustering analysis was performed to identify changes in the microbial population within the nosocomial environment. Enterobacter were identified using two platforms (MALDI-TOF Biotyper and VITEK MS). Antimicrobial susceptibility was tested by Vitek2 Compact and MIC50 and MIC90 was evaluated using GraphPad software. Clustering analysis was performed by MALDI-TOF and a dendrogram was built with both platforms and compared. The most frequent species isolated were Enterobacter cloacae and Enterobacter aerogenes with a gradual increase of Enterobacter asburiae in 2017. MALDI-TOF platforms showed a very good sensitivity and specificity except for E. asburiae identification that was reliable only by MALDI-TOF MS Biotyper. An increase of resistance for Enterobacter, confirmed by the isolation of extended spectrum beta-lactamase (ESBL) strains and the emergence of E. cloacae multidrug-resistant (MDR) and carbapenem resistant strains, was observed. A clonal route of transmission involving general surgery and geriatric wards was evidenced as previously described for Klebsiella pneumoniae MDR strains in the same nosocomial setting. These data represent an important source of information about the spreading of Enterobacter in the nosocomial environment.

Multi-drug resistant Pseudomonas aeruginosa nosocomial strains: Molecular epidemiology and evolution.

Pseudomonas aeruginosa causes a wide variety of nosocomial infections. In the study, phylogenetic, selective pressure analysis and homology modelling were applied to oprD efflux pump gene with the aim to characterize multi-drug resistant strains circulating in the nosocomial setting, their transmission dynamics and ongoing evolution. One hundred ninety-three consecutive inpatients with Pseudomonas aeruginosa infection were enrolled at the University Campus Bio-Medico of Rome, between January 2015 and December 2016. oprD gene was sequenced in 20 nosocomial multi-drug resistant P. aeruginosa strains. Phylogeographic, selective pressure, residue conservation analysis and homology modelling were performed. Clinical epidemiological data were extracted from patient medical records. Multi-drug resistant strains accounted for the 36% of total strains and were responsible of 20 cases of nosocomial infections. P. aeruginosa infections occurred prevalently in the West area, especially at the location IIIW and in the Geriatric ward. The time of the most recent common ancestor indicated that strains could have been introduced in the hospital since the end of the year 2009 with the most probable location in general surgery ward. By selective pressure analysis, 29 positions under diversifying selection have been identified and mapped onto the OprD model. Most of the observed residue substitutions are predicted to be destabilizing and some of them occurred in the Loops 2 and 3 that are involved in solute selection and carbapenem susceptibility. The molecular and evolutionary analysis of Multi-drug resistant strains circulating in the nosocomial setting may provide useful insights into the epidemiology and the mechanisms leading to resistance, contributing to infection control improvement.

A case of methicillin-resistant Staphylococcus aureus wound infection: phylogenetic analysis to establish if nosocomial or community acquired.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is rapidly increasing in both hospital and community settings. A 71-year-old man admitted at the Department of Orthopaedics and Trauma Surgery, University Campus Bio-Medico of Rome, with MRSA wound infection consequent to orthopedic surgery was studied and the MRSA transmission evaluated by phylogenetic analysis.

Klebsiella pneumoniae blaKPC-3 nosocomial epidemic: Bayesian and evolutionary analysis.

K. pneumoniae isolates carrying blaKPC-3 gene were collected to perform Bayesian phylogenetic and selective pressure analysis and to apply homology modeling to the KPC-3 protein. A dataset of 44 blakpc-3 gene sequences from clinical isolates of K. pneumoniae was used for Bayesian phylogenetic, selective pressure analysis and homology modeling. The mean evolutionary rate for blakpc-3 gene was 2.67×10-3 substitution/site/year (95% HPD: 3.4×10-4-5.59×10-3). The root of the Bayesian tree dated back to the year 2011 (95% HPD: 2007-2012). Two main clades (I and II) were identified. The population dynamics analysis showed an exponential growth from 2011 to 2013 and the reaching of a plateau. The phylogeographic reconstruction showed that the root of the tree had a probable common ancestor in the general surgery ward. Selective pressure analysis revealed twelve positively selected sites. Structural analysis of KPC-3 protein predicted that the amino acid mutations are destabilizing for the protein and could alter the substrate specificity. Phylogenetic analysis and homology modeling of blaKPC-3 gene could represent a useful tool to follow KPC spread in nosocomial setting and to evidence amino acid substitutions altering the substrate specificity.

Genetic diversity of hepatitis B virus (HBV) in Madagascar.

Hepatitis B virus (HBV) is a DNA virus belonging to Hepadnaviridae family. Chronic infection with HBV is one major risk factor of hepatic disease. In Madagascar, former studies classified the country as part of high endemic area, as HBV prevalence can reach 23% in general population. However, this prevalence differs largely between urban and rural areas and is estimated to be, respectively, 5% and 26%. The aims of the present study were to describe the genetic diversity of HBV strains from different regions of Madagascar, and to describe the viral gene flow throughout the country by using phylogenetic analysis. This is the first large-scale molecular and phylogenetic study analyzing HBV sequences from 28 different Malagasy areas, never sampled in the past. In this study, the most prevalent genotype/sub-genotypes was E. Migration analysis showed a gene flow from zone 3 (rural) to zone 2 (suburban), and a greater gene flow from the middle part of Madagascar to the north than to the south. It is important to study the HBV infections in Madagascar and to monitor the potential spread of this viral strain inside this country. J. Med. Virol. 88:2138-2144, 2016. © 2016 Wiley Periodicals, Inc.

Procalcitonin, MR-Proadrenomedullin, and Cytokines Measurement in Sepsis Diagnosis: Advantages from Test Combination.

BACKGROUND: Elevated cytokines levels correlate with sepsis severity and mortality but their role in the diagnosis is controversial, whereas Procalcitonin (PCT) has been largely used. Recently, the mid-regional proadrenomedullin (MR-proADM) has been combined with PCT for diagnosis optimization. In this study the combined measurement of PCT, MR-proADM, and cytokines in patients with sepsis was evaluated. METHODS: One hundred and four septic patients and 101 controls were enrolled. Receiver operating characteristic (ROC) analysis and multiple logistic regression were used to evaluate applicant markers for sepsis diagnosis. Markers with best Odds Ratio (OR) were combined, and the posttest probability and a composite score were computed. RESULTS: Based upon ROC curves analysis, PCT, MR-proADM, IL-6, IL-10, TNF-α, and MCP-1 were considered applicant for sepsis diagnosis. Among these PCT, MR-proADM , IL-6, and TNF-α showed the best OR. A better posttest probability was found with the combination of PCT with MR-proADM and PCT with IL-6 or TNF-α compared to the single marker. A composite score of PCT, MR-proADM, and TNF-α showed the best ROC curve in the early diagnosis of sepsis. CONCLUSION: The combination of PCT with other markers should expedite diagnosis and treatment of sepsis optimizing clinical management.

Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and Bayesian phylogenetic analysis to characterize Candida clinical isolates.

Clinical Candida isolates from two different hospitals in Rome were identified and clustered by MALDI-TOF MS system and their origin and evolution estimated by Bayesian phylogenetic analysis. The different species of Candida were correctly identified and clustered separately, confirming the ability of these techniques to discriminate between different Candida species. Focusing MALDI-TOF analysis on a single Candida species, Candida albicans and Candida parapsilosis strains clustered differently for hospital setting as well as for period of isolation than Candida glabrata and Candida tropicalis isolates. The evolutionary rates of C. albicans and C. parapsilosis (1.93×10(-2) and 1.17×10(-2)substitutions/site/year, respectively) were in agreement with a higher rate of mutation of these species, even in a narrow period, than what was observed in C. glabrata and C. tropicalis strains (6.99×10(-4) and 7.52×10(-3)substitutions/site/year, respectively). C. albicans resulted as the species with the highest between and within clades genetic distance values in agreement with the temporal-related clustering found by MALDI-TOF and the high evolutionary rate 1.93×10(-2)substitutions/site/year.

MALDI-TOF mass spectrometry and blakpc gene phylogenetic analysis of an outbreak of carbapenem-resistant K. pneumoniae strains.

Carbapenem-resistant Klebsiella pneumoniae isolates are an important cause of nosocomial infections. This study evaluated a rapid cost-saving method based on MALDI-TOF technology, was and compared it with phenotypic, genotypic and epidemiological data for characterization of KPC-Kp strains consecutively isolated during a supposed outbreak. Twenty-five consecutive KPC Klebsiella pneumoniae isolates were identified and clustered by the MALDI Biotyper (Bruker, Daltonics). To display and rank the variance within a data set, principal component analysis (PCA) was performed. ClinProTools models were generated to investigate the highest sum of recognition capability and cross-validation. A Class dendrogram of isolates was constructed using ClinproTool. MLST was performed sequencing gapA, infB, mdh, pgi, rpoB, phoE and tonB genes. blakpc and cps genes were typed. Phylogenetic analysis and genetic distance of the KPC gene were performed using the MEGA6 software. PCA analysis defined two clusters, I and II, which were identified in a dendrogram by both temporal split and different antimicrobial susceptibility profiles. These clusters were composed mostly of strains of the same sequence type (ST512), the most prevalent ST in Italy, and the same cps (type 2). In cluster II, blakpc genotype resulted more variable than in cluster I. Phylogenetic analysis confirmed the genetic diversity in both clusters supported by the epidemiological data. Our study confirms that MALDI-TOF can be a rapid and cost-saving method for epidemiological clustering of KPC K. pneumoniae isolates and its association with blakpc genotyping represents a reliable method to recognize possible clonal strains in nosocomial settings.

Turnaround time of positive blood cultures after the introduction of matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.

A comparative evaluation of the turnaround time (TAT) of positive blood culture before and after matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) introduction in the laboratory routine was performed. A total of 643 positive blood cultures, of which 310 before and 333 after MALDI-TOF technique introduction, were collected. In the post MALDI-TOF period, blood culture median TAT decreased from 73.53 hours to 71.73 for Gram-positive, from 64.09 hours to 63.59 for Gram-negative and from 115.7 hours to 47.62 for anaerobes. MALDI-TOF significantly decreased the TAT of anaerobes, for which antimicrobial susceptibility test is not routinely performed. Furthermore, the major advantage of MALDI-TOF introduction was the decrease of the time for pathogen identification (TID) independently from the species with an improvement of 93% for Gram-positive, 86% for Gram-negative and 95% for anaerobes. In addition, high species-level identification rates and cost savings than conventional methods were achieved after MALDI-TOF introduction.

Diagnostic and prognostic role of procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM) in bacterial infections.

Rapid diagnosis of bacterial infections is crucial for adequate antibiotic treatment. Serum molecules such as Procalcitonin (PCT) have been used as biomarkers of infection. Recently, the mid-regional pro-Adrenomedullin (MR-proADM) has been evaluated in combination with PCT for sepsis diagnosis. The diagnostic role of PCT and MR-proADM both in sepsis and in localized infections together with their contribution to effective antibiotic therapy has been evaluated. One hundred and eighty-two patients with bacterial infection has been enrolled: PCT and MR-proADM were measured at admission (T = 0), at 12-24 h (T = 1) and in the third or fifth day of antibiotic therapy (T = 3-5). ROC curve (receiver operating characteristic) and post-test probability were calculated. MR-proADM increased with the severity of the infection. PCT resulted significantly higher in sepsis than localized infection. After antibiotic therapy, PCT significantly decreased in localized respiratory infections and in sepsis, while MR-proADM decreased significantly after antibiotic therapy only in patients with severe sepsis/septic shock. The threshold values of PCT and MR-proADM were >0.1 ng/mL and >0.8 nmol/L, respectively. The combined use of PCT and MR-proADM increased the post-test probability of the diagnosis of bacterial infections compared to PCT alone. In conclusion, PCT and MR-proADM combination improves the diagnosis of bacterial infection and contribute to prognosis and antibiotic therapy effectiveness.