Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).

Introduction. Staphylococcus felis is a coagulase-negative staphylococcal species that is commonly isolated from healthy cats. Like other commensal staphylococci, S. felis can cause opportunistic infections, e.g. otitis externa, skin and urinary tract infections, in cats. Gap Statement. Several studies have reported within-household transmission between humans and pets and human infections caused by coagulase-positive staphylococci. However, human infections with coagulase-negative staphylococci of zoonotic origin are relatively rare. Methodology. Culture of a surgical site infection in a 58-year-old woman who underwent a laminectomy revealed dominant growth of S. felis . The three cats owned by the patient were sampled to investigate potential within-household transmission. S. felis isolates were sequenced to investigate the relatedness of the isolates and to look for virulence factors and host specific genes. Results. All cats were colonized with S. felis . Comparative genomics of the isolates showed that each cat was colonized with a distinct genotype. The patient’s isolate clustered with isolates of one of the cats. Sequence analysis of the studied isolates together with 29 publicly available S. felis genomes detected putative virulence factors that can be crucial in potential interspecies transmission. Conclusion. The current case is the first reported human infection caused by S. felis and highlights the zoonotic potential of this bacterial species. Evidence of cat-to-human transmission was shown by comparative genomics of isolates from the patient with isolates of her cats.

Background: Recent scientific reports on the use of high dose tigecycline monotherapy as a “drug of last resort” warrant further research into the use of this regimen for the treatment of severe multidrug-resistant, Gram-negative bacterial infections. In the current study, the therapeutic efficacy of tigecycline monotherapy was investigated and compared to meropenem monotherapy in a newly developed rat model of fatal lobar pneumonia–septicemia. Methods: A Klebsiella pneumoniae producing extended-spectrum β-lactamase (ESBL) and an isogenic variant producing K. pneumoniae carbapenemase (KPC) were used in the study. Both strains were tested for their in vitro antibiotic susceptibility and used to induce pneumonia–septicemia in rats, which was characterized using disease progression parameters. Therapy with tigecycline or meropenem was initiated at the moment that rats suffered from progressive infection and was administered 12-hourly over 10 days. The pharmacokinetics of meropenem were determined in infected rats. Results: In rats with ESBL pneumonia–septicemia, the minimum dosage of meropenem achieving survival of all rats was 25 mg/kg/day. However, in rats with KPC pneumonia–septicemia, this meropenem dosage was unsuccessful. In contrast, all rats with KPC pneumonia–septicemia were successfully cured by administration of high-dose tigecycline monotherapy of 25 mg/kg/day (i.e., the minimum tigecycline dosage achieving 100% survival of rats with ESBL pneumonia–septicemia in a previous study). Conclusions: The current study supports recent literature recommending high-dose tigecycline as a last resort regimen for the treatment of severe multidrug-resistant bacterial infections. The use of ESBL- and KPC-producing K. pneumoniae strains in the current rat model of pneumonia–septicemia enables further investigation, helping provide supporting data for follow-up clinical trials in patients suffering from severe multidrug-resistant bacterial respiratory infections.

An accurate diagnosis of invasive aspergillosis (IA) in patients with underlying hematological malignancies relies heavily on galactomannan detection. In this study, we compared the VirCLIA chemiluminescence immunoassay (CLIA) with the frequently used Platelia enzyme-linked immunosorbent assay (ELISA) on serum from hematology patients with suspected IA. Patients were categorized according to EORTC/MSGERC 2020 definitions into proven/probable IA and possible/no IA. The first cohort included 161 patients at four centers, and the VirCLIA manufacturer’s cutoff of 0.200 was evaluated. Next, the optimal cutoff was determined using the Youden’s index. In a second independent cohort of 189 patients from four centers, this optimal cutoff was evaluated again. In the first cohort, sensitivities and specificities for probable/proven IA were 21.1% and 100.0% for ELISA (1.0 cutoff) and 36.6% and 95.6% (0.5 cutoff), compared to 11.3% and 97.8% for CLIA (0.200 cutoff). In the second cohort, the sensitivities of ELISA and CLIA were comparable (ELISA ≥ 1.0: 33.3%, CLIA ≥ 0.200: 38.1%). The area under the ROC curve was lower for CLIA than for ELISA in the first cohort (65.0% vs 78.7%, P = 0.005) but comparable in the second cohort (79.5% vs 81.3%, P = 0.649). Youden’s index identified 0.100 as the optimal CLIA cutoff with sensitivities of 35.2% and 61.9% in cohorts 1 and 2, respectively, at slightly reduced specificities of 85.6% and 90.5%. While the sensitivity of both assays was low to moderate at best, in patients with a high pre-test probability, we suggest 0.100 as the cutoff for the VirCLIA assay. IMPORTANCE: This study demonstrates a comparable performance of the novel chemiluminescence immunoassay (CLIA) and the conventionally used enzyme-linked immunosorbent assay for galactomannan serum testing in hematological patients at high risk for invasive aspergillosis. In patients with a high pre-test probability, a lower CLIA cutoff of 0.100 is preferred.