Rethinking Combination Therapy for S. aureus bacteremia: A Fading Paradigm.

Staphylococcus aureus bacteremia presents clinical complexities, with prolonged duration associated with unfavorable outcomes. This research delves into unconventional treatments, such as combinations involving daptomycin, oxacillin, ceftaroline, and fosfomycin, with the aim of swiftly sterilizing bloodstream infection to reduce complications. Our examination of 30 MSSA bacteremia patients with infective endocarditis uncovers differing results between single-agent therapies (oxacillin or daptomycin) and combined treatment plans. Microbiologic clearance at the 72 hour mark demonstrates greater efficacy within the combination cohort (bacteremia persistence 29%) versus monotherapy (bacteremia persistence 78%). This limited case series suggests the potential superiority of combination therapy, prompting further investigations.

Time is running out. No excuses to delay implementation of antimicrobial stewardship programmes: impact, sustainability, resilience and efficiency through an interrupted time series analysis (2017-2022).

Introduction: The WHO declared antimicrobial resistance (AMR) a significant concern in 2014, sparking initiatives to ensure responsible antibiotic use. In human medicine, Antimicrobial Stewardship Programmes (ASPs) in hospitals play a pivotal role in combating AMR. Although evidence supports the effectiveness of ASPs in optimizing antimicrobial use, often the lack of resources becomes an excuse to limit their dissemination and use. This paper provides a comprehensive report on a 6-year analysis of an ASP implemented in a healthcare region in north-east Italy. Methods: A retrospective data collection was conducted to assess the programme's impact on antibiotic consumption expressed as DDDs/100 patient-days, its sustainability over time, resilience during the COVID-19 pandemic and the efficiency of the ASP (relationship between workload and human resources). Results: A substantial overall reduction in antibiotic consumption (-14%), particularly in fluoroquinolones (-64%) and carbapenems (-68%), was demonstrated, showcasing the programme's impact. Sustainability was confirmed through enduring trends in antibiotic consumption and ecological analysis over time. The ASP demonstrates resilience by maintaining positive trends even amid the challenging COVID-19 pandemic. Efficiency was underscored by an increase in on-site consultations despite consistent human resources until 2021. Conclusions: This study offers insights into the prolonged success of a resource-efficient ASP, emphasizing the crucial role of long-term commitment in fostering responsible antibiotic use in the context of global health challenges such as AMR.

The Management of Recurrent Urinary Tract Infection: Non-Antibiotic Bundle Treatment.

Recurrent urinary tract infections (rUTIs) are a common condition with high morbidity and negatively impact the quality of life. They account for approximately 25% of all antibiotic prescriptions and are a public health concern in an era of increasing multidrug-resistant organisms (MDROs). Several non-antibiotic treatment strategies have been tried to curb antimicrobial use, and many are effective to some degree, but no experience testing multimodal interventions. We created a "care bundle" consisting of behavioral interventions, vaginal and oral probiotics, D-mannose, and cranberry to be followed for six months. We enrolled women with rUTIs over three years. Changes in urinary tract infections, antibiotic use, chronic symptoms, and quality of life were compared in the six months before and after participation in the study. Forty-seven women were enrolled in the study, six of whom were excluded from the final analysis. We observed a 76% reduction in urinary tract infections (p < 0.001) and a reduction in total antibiotic exposure of more than 90% (p < 0.001); all chronic symptoms showed a trend toward reduction. Adherence to the bundle was high (87.2%). Overall, 80.5% of women experienced an improvement in their quality of life. In our experience, a bundle protocol is effective in reducing recurrences and antimicrobial use in a cohort of women with rUTIs and results in a subjective improvement in chronic symptoms and quality of life. Further research with larger sample size is needed to confirm these findings.

Dalbavancin in catheter-related bloodstream infections: a pilot study.

Background: Catheter-related bloodstream infections (CRBSI) represent a frequent complication of vascular catheterization, with high morbidity, mortality, and associated costs. Most infections are caused by Gram-positive bacteria; thus dalbavancin, a new long-acting lipoglicopeptide, may have a role in early patient discharge strategies optimizing treatment and reducing overall costs. Methods: In this small pilot feasibility study, we assessed the efficacy and safety of a "single step" treatment strategy combining dalbavancin administration (1500 mg IV single dose), catheter removal, and early discharge in adult patients admitted to medical wards in a three-year period. Results: We enrolled sixteen patients with confirmed Gram-positive CRBSI, with a mean age of 68 years and relevant comorbidities (median Charlson Comorbidity index=7). The most frequent causative agents were staphylococci, with 25% of methicillin-resistant strains, and the majority of infected devices were short term central venous catheter (CVC) and peripherally inserted central catheter (PICC). Ten out of sixteen patients had been treated empirically before dalbavancin administration. The mean time from dalbavancin administration to discharge was 2 days; none of the patients had adverse drug-related reactions; at 30- and 90-day follow-up, no patients have been readmitted to the hospital due to bacteraemia recurrence. Conclusions: Our results indicate that single-dose dalbavancin is highly effective, well-tolerated, and cost-saving for Gram-positive CRBSI.

Antimicrobial Stewardship in the Covid-19 Pandemic.

During COVID-19 pandemic, implementing and maintaining an antimicrobial stewardship protocol obtained both low rates of MDR microorganisms and low antimicrobial use in an 800-bed hospital network in northern Italy. Infectious diseases specialist consulting was crucial to maintain this protocol active.

Epidemiology of respiratory virus before and during COVID-19 pandemic.

The COVID pandemic has forcefully turned the spotlight on the importance of the diagnosis of respiratory virus infections. Viruses have always been a frequent and common cause of respiratory tract infections. Rapid molecular diagnostics applied to the diagnostics of respiratory virus infections has revolutionized microbiology laboratories only a few years ago. Few studies illustrate the epidemiology of respiratory viruses, and fewer still those that have compared the pre-pandemic to the pandemic period. During the first year of the pandemic (2020-2021) it was clear to everyone to witness a sudden disappearance of the circulation of all the other respiratory viruses, especially those typically isolated during the winter time, such as RSV and Influenza virus. In our study we wanted to verify this phenomenon and to study the epidemiology of our local reality, analyzing three consecutive flu seasons (2018-2019, 2019-2020, 2020-2021). The results lead us to note that the prevalence of positivity to respiratory virus infections went from 49.8% (2018-2019) and 39% (2019-2020) to 13.4% (2020-2021). This decrease is at least partly attributable to the security measures adopted (social distancing and mask), but it certainly opens up new scenarios when the restriction measures will be terminated. We believe such studies can provide real-world evidence of the effectiveness of public health interventions implemented during current and future pandemics.

Molecular diagnosis of SARS-Cov-2, performances and throughput by Direct RT-PCR.

The Covid-19 pandemic has required all laboratories to rapidly and unexpectedly reorganize to cope with the increase in requests for tests in rapid response times and, not least, to provide the shortening of molecular reagents. In order to validate an accurate, faster and cheaper method suitable for large-scale diagnosis of SARS-CoV-2, we evaluated a simplified workflow by Direct RT-PCR on 181 nasopharyngeal swabs on Seegene's automated platform. Direct RT-PCR ensured 99% overall concordance versus standard RNA RT-PCR in samples with Ct values under 35, saving 100% on extraction reagents and providing an approximately three-fold increase in productivity in 24 hours.

A new molecular method for rapid etiological diagnosis of sepsis with improved performance.

The value of blood cultures for confirming the clinical diagnosis of sepsis is suboptimal. There is growing interest in the potential of real-time PCR technology by detection of minute amounts of pathogen DNA in patient blood samples with results available within 4-6 h. Adopting a two-step approach, we evaluated the compliance of two versions of the MicrobScan assay on a total of 748 patients with suspected bloodstream infections. The results obtained with a second version of the MicrobScan assay are characterized by increased specificity (from 95.1 to 98.2%) and sensitivity (from 76.7 to 85.1), increased throughput and the possibility of simultaneously testing different kinds of samples collected from the potential sites of infection and utilizing different syndromic panels.

Epidemiological and clinical features of imported malaria at the three main hospitals of the Friuli-Venezia Giulia Region, Italy.

BACKGROUND: Imported malaria cases continue to occur in non-endemic regions among travellers returning from tropical and subtropical countries. At particular risk of acquiring malaria is the group of travellers identified as immigrants who return to their home country with the specific intent of visiting friends or relatives (VFRs) and who commonly believe they are immune to malaria and fail to seek pre-travel advice. Our aim was to review the current trends of imported malaria in the three main hospitals of the Friuli-Venezia Giulia region (FVG), North Eastern Italy, focusing in particular on patient characteristics and laboratory findings. METHODS: In this retrospective study, we examined all malaria cases among patients admitted from January 2010 through December 2014 to the emergency department of the three main hospitals located in FVG. RESULTS: During the 5-year study period from 2010 to 2014, there were a total of 140 patients with a diagnosis of suspected malaria and who received microscopic confirmation of malaria. The most common species identified was P. falciparum, in 96 of 140 cases (69%), followed by P. vivax (13%), P. ovale (4%), P. malariae (4%), and mixed infection (4%). The most common reason for travel was VFRs (54%), followed by work (17%), and recent immigration (15%). Moreover, 78% of all patients took no chemoprophylaxis, 80 (79%) of whom were foreigners. Notably, the percentage of Italian travellers who took chemoprophylaxis was only 20% (8 of 39 Italian cases), and the regimen was appropriate in only four cases. Parasitaemia greater than 5% was observed in 11 cases (10%), all due to P. falciparum infection. CONCLUSIONS: We highlight that VFRs have the highest proportion of malaria morbidity and the importance of improving patient management in this category. These data are useful for establishing appropriate malaria prevention measures and recommendations for international travellers.

Co-production of NDM-1 and OXA-232 by ST16 Klebsiella pneumoniae, Italy, 2016.

Carbapenem-resistant Klebsiella pneumoniae strains, New Delhi metallo-ß-lactamase-1 producers, are still rare in Italy, being endemic in Southeast Asiatic region. In October 2016, a multidrug-resistant K. pneumoniae was isolated from blood and urine of an Italian long-hospitalized patient with urosepsis without travel history abroad. To the best of our knowledge, this is the first report of bacteremia caused by an ST16 K. pneuomoniae New Delhi metallo-ß-lactamase-1 and OXA-232 co-producing carbapenemase, in Italy.

Technical note: Discard the specimen collection swab directly at point of care to improve extensive automated processing in clinical microbiology laboratories.

We compared, in terms of microorganisms recovery, the discard of specimen collection swab, after swirling into its medium, directly at point of care, with its placing into the medium and vortexing on arrival in the laboratory. Our results show that these two procedures are overlapped in terms of bacterial recovery.

Liquid based microbiological transport systems: conformity assessment of two commercial devices.

We compared two types of liquid-based microbiology devices for microorganism viability according to standardized quantitative elution method CLSI M40-A2. The eSwab® met CLSI acceptance criteria of viability maintenance for all microorganisms tested. The Σ-Transwab® failed to meet CLSI acceptance criteria for Peptostreptococcus anaerobius, Prevotella melaninogenica, Fusobacterium nucleatum and Haemophilus influenzae.

Direct molecular detection of pathogens in blood as specific rule-in diagnostic biomarker in patients with presumed sepsis: our experience on a heterogeneous cohort of patients with signs of infective systemic inflammatory response syndrome.

The practical value of blood cultures in the diagnosis of sepsis is impaired by a delay in the turnaround time to result and by the fact that blood culture positive can be found for only about 30% of these patients. Conventional laboratory signs of sepsis and acute phase protein biomarkers are sensitive and easy to use, but often also very nonspecific. Molecular diagnostic reflects currently the most promising avenue to decrease time to result and to influence decision making for antibiotic therapy in the septic host. In this study, we wish to highlight the impact of the LightCycler SeptiFast, a multipathogen probe-based real-time polymerase chain reaction, in the rapid etiological diagnosis of sepsis in patients with clinical and laboratory signs of bloodstream infections. We have evaluated prospectively 830 adult patients with suspected bloodstream infection and at least two criteria of systemic inflammatory response syndrome. In more than 50% of critically ill patients strongly suspected of having sepsis, we arrived to an etiological diagnosis only by the molecular method in a median time of 15 h, with specificity and predictive positive values of 96% and 94%, respectively. We highlight the role of DNAemia as time-critical, high-specificity, etiological, non-culture-based rule-in diagnostic biomarker in patients with presumed sepsis.

When should adenoviral non-gonococcal urethritis be suspected? Two case reports.

The impact of Adenovirus as agent of non-gonococcal urethritis (NGU) is still poorly documented in the literature. We describe two cases showing that adenoviral infection should be reasonably hypothesized in men with dysuria and scant urethral discharge in addition to meatus inflammation and/or edema (meatitis) or conjunctivitis. Case 1: a 55-year-old man came to our observation in July 2012 referring a 5-day-history of intense dysuria and scant mucoid urethral discharge. Physical examination revealed the urethral discharge referred, but also modest meatitis and an intense conjunctival hyperemia on his right eye. Adenoviral infection was investigated and Adenovirus DNA (type 37) was detected in both the urethral and conjunctival swabs. Case 2: a 43-year-old man with intense dysuria, started 4-5 days earlier, came to our attention with his wife in August 2012. Scant urethral mucoid secretions, severe meatal inflammation of the male patient were revealed during physical examination. His wife instead complained of a 2-day history of intense burning eyes. Adenoviral infection was investigated and Adenovirus DNA (type 37) was positive both in the male urethral swab and in his wife's conjunctival swab. Adenovirus seems to cause a distinct and recognisable clinical syndrome in men presenting with urethritis. Studies on the prevalence and role of Adenovirus as a causative agent of urethritis are limited. Moreover, as rapid advanced molecular microbiology is now available, we believe that extending the search to Adenovirus in sexually active men with dysuria, scant discharge in addition to meatitis or conjunctivitis, should be a useful approach improving our understanding about adenoviral NGU, and especially avoiding or stopping unnecessary empirical antibiotic therapy.

Methicillin-resistant Staphylococcus aureus infection rate after implementation of an antibiotic care bundle based on results of rapid molecular screening.

AIM: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for subsequent invasive MRSA infection, particularly in patients admitted to critical areas. We conducted a surveillance among patients admitted to our Intensive Care Unit (ICU) to determine whether the implementation of a specific MRSA antibiotic care bundle (ACB) based on rapid molecular screening for MRSA and de-colonization, reduced the total MRSA infection rate. MATERIALS AND METHODS: A total of 431 and 577 nasal swabs were obtained from ICU patients at admission from April 2009 through December 2010 (pre-ACB period) and, after the bundle implementation, from January 2011 through December 2012 (post-ACB period), respectively. Nasal swabs were analyzed by the rapid molecular test Xpert MRSA. All patients were followed-up during their whole ICU stay to determine whether they developed MRSA infection. RESULTS: Overall, 31 out of 431 (7.1%) patients were colonized with MRSA at admission during the pre-ACB period and 49 out of 577 (8.4%) were colonized with MRSA during the post-ACB period. The rate of MRSA infection in ICU significantly declined from 2% in pre-ACB to 0.3% in post-ACB, with a total decrease of 100% in two consecutive semesters between July 2011 and July 2012 (p<0.001). CONCLUSION: The analysis demonstrated a significant decline in MRSA infections following the introduction of active rapid molecular surveillance and the specific ACB at our ICU and in the risk associated with MRSA bacteremia.

An antibiotic care bundle approach based on results of rapid molecular screening for nasal carriage of methicillin-resistant Staphylococcus aureus in the intensive care unit.

The potential role of active methicillin-resistant Staphylococcus aureus (MRSA) surveillance in the intensive care unit (ICU), has been recently proposed as a guide for antibiotic treatment in patients suspected of being infected with MRSA by using an antibiotic care bundle (ACB) approach. A group of 376 consecutive ICU patients were prospectively screened for nasal carriage of MRSA using a real-time polymerase chain reaction test. The study group consisted of 244 (64.9%) males and (35.1%) females, with a median age of 64 (range 17-95 years). Overall, 26 (6.9%) patients were positive for MRSA, while 350 (93.1%) were MRSA-negative. No difference was observed in gender and age between groups. During ICU stay, 9 (2.4%) patients developed generalized MRSA infection, of whom 8 out of 26 (30.8%) were MRSA-carriers and one out of the 350 (0.3%) was MRSA-negative. Thus, a strong relationship between MRSA infection and MRSA carriage (relative risk=107.7, 95% confidence interval=14.0-828.5, p<0.0001) was found. Subsequently, in our ICU, we developed and introduced a new ACB approach based on rapid nasal screening results for improving the management of critically ill patients. The use of anti-MRSA agents should be re-evaluated daily on the basis of clinical and laboratory features, with positive cultures from sterile site or signs of active infection supporting prolongation of empirical treatment. On the contrary, MRSA-negative clinical cultures support a de-escalation strategy. In conclusion, the early identification of MRSA-carriers using a rapid molecular screening is safe and accurate, allowing MRSA-positive patients, who will more likely develop MRSA infections, to be detected.

Molecular diagnosis of Staphylococcus aureus prosthetic aortic graft infection: a case report.

INTRODUCTION: Aortic graft infection is a widely debated topic in the literature, it represents about 1% of post-surgical complications and is associated with a high complication and mortality rate. In most cases, such infections are treated empirically because patients are already under antibiotic coverage so as not to allow isolation of the pathogen. The literature in this regard is very attentive to new molecular diagnostic possibilities, and especially the operating of such complications in a precise diagnostic algorithm and management of the patient. REPORT: We present the case of a 62-year-old patient with abdominal aortic aneurysms (AAA) treated in 2004 by endovascular repair of abdominal aortic aneurysms (EVAR). In 2009, a type II endoleak (the most frequent complication in this kind of surgery) was treated by CT-guided direct puncture and embolization of aneurysm, due to progressive enlargement of the aortic aneurism sac during annual follow-up. After nine days the patient was hospitalized for septic fever. DISCUSSION: When traditional culture does not allow microbiological diagnosis, molecular tests may permit results to be obtained that can change the effective therapeutic intervention, with a decisive impact on patient outcome.

Evaluation of the Sysmex UF1000i flow cytometer for ruling out bacterial urinary tract infection.

BACKGROUND: Urine culture is one of the most frequently requested tests in microbiology, and it represents the gold standard for the diagnosis of UTIs. Considering the high prevalence of negative results and the long TAT of the culture test, the use of a rapid and reliable screening method is becoming more and more important, as it reduces the workload, the TAT of negative results, and above all, unnecessary antibiotic prescription. METHODS: The Sysmex UF1000i is a new urine flow cytometry analyzer capable of quantifying urinary particles, including BACT, WBCs, and YLCs. To evaluate the analytical performance of the UF1000i as a method for ruling out UTIs, we examined 1349 urine samples and compared the UF1000i results with standard urine culture results. RESULTS: With instrument cut-off values of 170BACTx10(6)/L and 150WBCsx10(6)/L, we obtained a sensitivity of 98.8%, a specificity of 76.5%, a NPV of 99.5%, and four false negative results (1.2%), avoiding the culture of 57.1% of samples. CONCLUSION: The Sysmex UF1000i was capable of improving the efficiency of a routine microbiology laboratory by processing 100samples/h and providing negative results in a few minutes, thus reducing unnecessary testing with an acceptable number of false negative results. In addition, the preliminary evaluation of B_FSC and B_FLH parameters from bacteria histograms seems to be useful for the distinction of bacterial strains detected (Gram-negatives versus Gram-positives). In fact when B_FSC was less than 30 ch, it allowed the distinction of Gram-negative bacteria in 97% of the samples.