Despite being members of gut microbiota,
are associated with many severe infections such as bloodstream infections. The β-lactam drugs have been the cornerstone of antibiotic therapy for such ...infections. However, the overuse of these antibiotics has contributed to select β-lactam-resistant
isolates, so that β-lactam resistance is nowadays a major concern worldwide. The production of enzymes that inactivate β-lactams, mainly extended-spectrum β-lactamases and carbapenemases, can confer multidrug resistance patterns that seriously compromise therapeutic options. Further, β-lactam resistance may result in increases in the drug toxicity, mortality, and healthcare costs associated with
infections. Here, we summarize the updated evidence about the molecular mechanisms and epidemiology of β-lactamase-mediated β-lactam resistance in
, and their potential impact on clinical outcomes of β-lactam-resistant
infections.
The emergence of SARS-CoV-2 variants is jeopardizing the effectiveness of current vaccines and limiting the application of monoclonal antibody-based therapy for COVID-19 (refs.
). Here we analysed ...the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to investigate the nature of the B cell and antibody response at the single-cell level. Almost 6,000 cells were sorted, over 3,000 cells produced monoclonal antibodies against the spike protein and more than 400 cells neutralized the original SARS-CoV-2 virus first identified in Wuhan, China. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants escaped almost 70% of these antibodies, while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part, this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in people who were convalescent and generated potent and broadly neutralizing antibodies. Our data suggest that people who are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control emerging SARS-CoV-2 variants.
is still one of the most threatening pathogens responsible for serious hospital-acquired infections. It is intrinsically resistant to many antimicrobial agents and additional acquired resistance ...further complicates the management of such infections. High rates of combined antimicrobial resistance persist in many countries, especially in the eastern and south-eastern parts of Europe. The aim of this narrative review is to provide a comprehensive assessment of the epidemiology, latest data, and clinical evidence on the current and new available drugs active against
isolates with limited treatment options. The latest evidence and recommendations supporting the use of ceftolozane-tazobactam and ceftazidime-avibactam, characterized by targeted clinical activity against a significant proportion of
strains with limited treatment options, are described based on a review of the latest microbiological and clinical studies. Cefiderocol, with excellent in vitro activity against
isolates, good stability to all β-lactamases and against porin and efflux pumps mutations, is also examined. New carbapenem combinations are explored, reviewing the latest experimental and initial clinical evidence. One section is devoted to a review of new anti-pseudomonal antibiotics in the pipeline, such as cefepime-taniborbactam and cefepime-zidebactam. Finally, other "old" antimicrobials, mainly fosfomycin, that can be used as combination strategies, are described.
Purpose
Candida
is the most common cause of severe yeast infections worldwide, especially in critically ill patients. In this setting, septic shock attributable to
Candida
is characterized by high ...mortality rates. The aim of this multicenter study was to investigate the determinants of outcome in critically ill patients with septic shock due to candidemia.
Methods
This was a retrospective study in which patients with septic shock attributable to
Candida
who were treated during the 3-year study period at one or more of the five participating teaching hospitals in Italy and Spain were eligible for enrolment. Patient characteristics, infection-related variables, and therapy-related features were reviewed. Multiple logistic regression analysis was performed to identify the risk factors significantly associated with 30-day mortality.
Results
A total of 216 patients (mean age 63.4 ± 18.5 years; 58.3 % males) were included in the study. Of these, 163 (75 %) were admitted to the intensive care unit. Overall 30-day mortality was 54 %. Significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, dysfunctional organs, and inadequate antifungal therapy were compared in nonsurvivors and survivors. No differences in survivors versus nonsurvivors were found in terms of the time from positive blood culture to initiation of adequate antifungal therapy. Multivariate logistic regression identified inadequate source control, inadequate antifungal therapy, and 1-point increments in the APACHE II score as independent variables associated with a higher 30-day mortality rate.
Abstract
Background
Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections ...secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of
Staphylococcus aureus
ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19.
Methods
We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed.
Results
We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%;
p
= 0.01), methicillin-resistant (65.0% vs 27.5%;
p
< 0.01) or bacteremic (47.5% vs 6.3%;
p
< 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (
p
= 0.12), clinical cure (
p
= 0.20) and microbiological eradication (
p
= 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance,
R
2
0.15349;
p
< 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8;
p
< 0.01). Interestingly, we found that
S. aureus
(log
2
fold change, 29.5),
Streptococcus anginosus
subspecies
anginosus
(log
2
fold change, 24.9), and
Olsenella
(log
2
fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non–COVID-19 group of SA-VAP patients.
Conclusions
In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.
Background The increasing frequency of ventilator-associated pneumonia (VAP) caused by colistin-only susceptible (COS) gram-negative bacteria (GNB) is of great concern. Adjunctive aerosolized (AS) ...colistin can reportedly increase alveolar levels of the drug without increasing systemic toxicity. Good clinical results have been obtained in patients with cystic fibrosis, but conflicting data have been reported in patients with VAP. Methods We conducted a retrospective, 1:1 matched case-control study to evaluate the efficacy and safety of AS plus IV colistin vs IV colistin alone in 208 patients in the ICU with VAP caused by COS Acinetobacter baumannii , Pseudomonas aeruginosa , or Klebsiella pneumoniae. Results Compared with the IV colistin cohort, the AS-IV colistin cohort had a higher clinical cure rate (69.2% vs 54.8%, P = .03) and required fewer days of mechanical ventilation after VAP onset (8 days vs 12 days, P = .001). In the 166 patients with posttreatment cultures, eradication of the causative organism was also more common in the AS-IV colistin group (63.4% vs 50%, P = .08). No between-cohort differences were observed in all-cause ICU mortality, length of ICU stay after VAP onset, or rates of acute kidney injury (AKI) during colistin therapy. Independent predictors of clinical cure were trauma-related ICU admission ( P = .01) and combined AS-IV colistin therapy ( P = .009). Higher mean Simplified Acute Physiology Score II ( P = .002) and Sequential Organ Failure Assessment ( P = .05) scores, septic shock ( P < .001), and AKI onset during colistin treatment ( P = .04) were independently associated with clinical failure. Conclusions Our results suggest that AS colistin might be a beneficial adjunct to IV colistin in the management of VAP caused by COS GNB.
Very few data exist on risk factors for developing biofilm-forming Candida bloodstream infection (CBSI) or on variables associated with the outcome of patients treated for this infection.
We ...identified 207 patients with CBSI, from whom 84 biofilm-forming and 123 non biofilm-forming Candida isolates were recovered. A case-case-control study to identify risk factors and a cohort study to analyze outcomes were conducted. In addition, two sub-groups of case patients were analyzed after matching for age, sex, APACHE III score, and receipt of adequate antifungal therapy. Independent predictors of biofilm-forming CBSI were presence of central venous catheter (odds ratio OR, 6.44; 95% confidence interval 95% CI, 3.21-12.92) or urinary catheter (OR, 2.40; 95% CI, 1.18-4.91), use of total parenteral nutrition (OR, 5.21; 95% CI, 2.59-10.48), and diabetes mellitus (OR, 4.47; 95% CI, 2.03-9.83). Hospital mortality, post-CBSI hospital length of stay (LOS) (calculated only among survivors), and costs of antifungal therapy were significantly greater among patients infected by biofilm-forming isolates than those infected by non-biofilm-forming isolates. Among biofilm-forming CBSI patients receiving adequate antifungal therapy, those treated with highly active anti-biofilm (HAAB) agents (e.g., caspofungin) had significantly shorter post-CBSI hospital LOS than those treated with non-HAAB antifungal agents (e.g., fluconazole); this difference was confirmed when this analysis was conducted only among survivors. After matching, all the outcomes were still favorable for patients with non-biofilm-forming CBSI. Furthermore, the biofilm-forming CBSI was significantly associated with a matched excess risk for hospital death of 1.77 compared to non-biofilm-forming CBSI.
Our data show that biofilm growth by Candida has an adverse impact on clinical and economic outcomes of CBSI. Of note, better outcomes were seen for those CBSI patients who received HAAB antifungal therapy.
We aimed to describe the characteristics of patients with Staphylococcus aureus bacteremia and to evaluate the risk factors associated with early (7-day) and late (30-day) mortality. We performed an ...observational study including all consecutive episodes of Staphylococcus aureus bacteremia diagnosed at two Italian university hospitals during 2010-2014. A total of 337 patients were included. Mean age was 69 years (range, 57-78) and 65% were males. Methicillin-resistant S. aureus (MRSA) was identified in 132/337 (39%)cases. Overall 7- and 30-day mortality were 13% and 26%, respectively. Early mortality was associated with increased Charlson scores (OR 1.3, 95% CI 1.1-1.5), MRSA bacteremia (OR 3.2, 95% CI 1.4-8.1), presentation with septic shock (OR 13.5, 95% CI 5.4-36.4), and occurrence of endocarditis (OR 4.5, 95%CI 1.4-14.6). Similar risk factors were identified for late mortality, including increased Charlson scores (OR 1.2, 95% CI 1.1-1.4), MRSA bacteremia (OR 2.1, 95% CI 1.2-3.9), presentation with septic shock (OR 4, 95%CI 1.7-9.7), occurrence of endocarditis (OR 3.8, 95% CI 1.4-10.2) as well as Child C cirrhosis (OR 3.9, 95% CI 1.1-14.4) and primary bacteremia (OR 2.5, 95%CI 1.3-5). Infectious disease consultation resulted in better outcomes both at 7 (OR 0.1, 95% CI 0.05-0.4) and at 30 days (OR 0.4, 95% CI 0.2-0.7). In conclusion, our study highlighted high rates of MRSA infection in nosocomial Staphylococcus aureus bacteremia. Multiple comorbidities, disease severity and methicillin-resistance are key factors for early and late mortality in this group. In patients with Staphylococcus aureus bacteremia, infectious disease consultation remains a valuable tool to improve clinical outcome.
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