Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme (AESOP) Annual Report 2020.

From 1 January to 31 December 2020, forty-nine institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aims of AESOP 2020 were to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial-resistant, and to characterise the molecular epidemiology of the E. faecium isolates. Of the 1,230 unique episodes of enterococcal bacteraemia investigated, 93.9% were caused by either E. faecalis (54.2%) or E. faecium (39.7%). Ampicillin resistance was not detected in E. faecalis but was detected in 88.2% of E. faecium . Vancomycin non-susceptibility was detected in 0.2% of E. faecalis and 32.6% of E. faecium . Overall, 35.2% of E. faecium harboured vanA and/or vanB genes. For the vanA/B positive E. faecium isolates, 38.8% harboured the vanA gene, 60.6% the vanB gene, and 0.6% harboured both vanA and vanB . Although the percentage of E. faecium bacteraemia isolates was significantly lower than that detected in the 2019 AESOP (presumably due to the COVID-19 elective surgery restrictions placed on hospitals), it remains substantially higher than that recorded in most European countries. The E. faecium isolates detected consisted of 71 multilocus sequence types (STs), with 81.7% of these isolates classified into eight major STs each containing ten or more isolates. All major STs belonged to clonal cluster 17 (CC17), a major hospital-adapted polyclonal E. faecium cluster. The major STs (ST17, ST1424, ST80, ST796, ST78, ST1421, ST555 and ST117) were found across most regions of Australia. The predominant clone was ST17, which was identified in all regions except the Northern Territory. Overall, 40.9% of isolates belonging to the eight major STs harboured the vanA or vanB gene. The AESOP 2020 has shown enterococcal bacteraemia episodes in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin-resistant vanA - or vanB -positive E. faecium which have limited treatment options.

Aminopenicillins for treatment of ampicillin-resistant enterococcal urinary tract infections.

PURPOSE: The purpose of this review is to describe the theory behind and data supporting use of aminopenicillins in the treatment of ampicillin-resistant enterococcal urinary tract infections. SUMMARY: Aminopenicillin concentrations in the urine may be high enough to achieve bacterial eradication and clinical cure for infections affecting the lower genitourinary tract, even in the context of in vitro resistance based on established susceptibility breakpoints. A literature search was conducted to identify original research articles describing the use of aminopenicillins in the treatment of urinary tract infections caused by ampicillin-resistant Enterococcus species. Three published retrospective cohort studies were identified, all of which reported that aminopenicillins had similar rates of clinical cure as other antibiotic classes prescribed for the treatment of enterococcal urinary tract infections. CONCLUSION: Both pharmacokinetic/pharmacodynamic principles and limited retrospective clinical data support the use of aminopenicillins in the treatment of lower urinary tract infections caused by Enterococcus species, even when the isolates have a minimum inhibitory concentration that exceeds the susceptibility breakpoint.

Role of membrane proteins in bacterial resistance to antimicrobial peptides.

Several natural antimicrobial peptides (AMPs), including the novel semisynthetic lipoglycopeptide antibiotics telavancin, dalbavancin, and oritavancin, have been approved for clinical use to address the growing problem of multiple antibiotic-resistant Gram-positive bacterial infections. Nevertheless, the efficacy of these antibiotics has already been compromised. The SARS-CoV-2 pandemic led to the increased clinical use of all antibiotics, further promoting the development of bacterial resistance. Therefore, it is critical to gain a deeper understanding of the role of resistance mechanisms to minimize the consequential risks of long-term antibiotic use and misuse. Here, we summarize for the first time the current knowledge of resistance mechanisms that have been shown to cause resistance to clinically used AMPs, with particular focus on membrane proteins that have been reported to interfere with the activity of AMPs by affecting the binding of AMPs to bacteria.

Real-World Use of Dalbavancin in the Era of Empowerment of Outpatient Antimicrobial Treatment: A Careful Appraisal Beyond Approved Indications Focusing on Unmet Clinical Needs.

Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable.

Bacteremia caused by Anaerococcus SPP: Is this an underdiagnosed infection?

The objectives of this study were to report 10 episodes of clinically significant bacteremia caused by species of the genus Anaerococcus isolated between July 2018 and February 2021 from the microbiology laboratory of a tertiary hospital in Granada (Spain). None of the isolates were identified by MALDI-TOF MS, and the definitive species identification was performed by 16 S rRNA gene sequencing. No reference spectra of the Anaerococcus species were present in the MALDI-TOF MS database. Eight isolates were finally identified as A. octavius, one isolate as A. tetradius and the other as A. urinomassiliensis. The majority of these infections were seen in patients aged >70 years. Risk factors for anaerobic infection were observed in eight patients, especially diabetes mellitus, surgery, and the presence of cancer. Fever was present in all patients. Three patients died, but only one death was attributed to the infection. Mean detection time of positive blood cultures was 47.5 h (range 24-92 h). Antimicrobial susceptibility to penicillin, amoxicillin-clavulanate, imipenem, moxifloxacin, clindamycin, metronidazole, and piperacillin-tazobactam was tested using the gradient diffusion technique and EUCAST breakpoints (except for moxifloxacin). No resistance to amoxicillin-clavulanate, metronidazole, imipenem, or piperacillin-tazobactam was detected; however, the majority of isolates were resistant to clindamycin. When MALDI-TOF MS does not provide a correct identification at genus or species level, as in some isolates of Gram-positive anaerobic cocci, microbiologists should perform an additional confirmatory technique, such as gene sequencing analysis, to obtain a definitive diagnosis.

The role of dalbavancin for Gram positive infections in the COVID-19 era: state of the art and future perspectives.

INTRODUCTION: The COVID-19 pandemic has dramatically challenged the national health systems worldwide in the last months. Dalbavancin is a novel antibiotic with a long plasmatic half-life and simplified weekly administration regimens, thus representing a promising option for the outpatient treatment of Gram-positive infections and the early discharge of hospitalized patients. Dalbavancin is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Many preliminary data seem to support its use in other indications, such as osteomyelitis, prosthetic joint infections, and infective endocarditis. AREAS COVERED: A search in the literature using validated keywords (dalbavancin, Gram-positive infections, Gram-positive cocci, ABSSSI, intravenous treatment, and long-acting antibiotics) was conducted on biomedical bibliographic databases (PubMed and Embase) from 2004 to 30 September 2020. Results were analyzed during two consensus conferences with the aim to review the current evidence on dalbavancin in Gram-positive infections, mainly ABSSSI, osteomyelitis, and infective endocarditis, highlight the main limitations of available studies and suggest possible advantages of the molecule. EXPERT OPINION: The board identifies some specific subgroups of patients with ABSSSIs who could mostly benefit from a treatment with dalbavancin and agrees that the design of homogenous and robust studies would allow a broader use of dalbavancin even in other clinical settings.

Challenges in the diagnosis and management of Granulicatella elegans endocarditis in a 9-year-old child.

A 9-year-old child, with a background of repaired pulmonary atresia and Ebstein's anomaly, presented with fever, night sweats and lethargy. Blood cultures grew Granulicatella elegans, a nutritionally variant Streptococcus and known cause of infective endocarditis (IE). Echocardiogram revealed no clear vegetation, but increased stenosis of the right ventricle to pulmonary artery conduit. The child was successfully managed with high-dose benzylpenicillin, completing 2 weeks in the hospital, and was discharged to complete the final 4 weeks of therapy with ceftriaxone in the community, as per European Society of Cardiology guidance. IE caused by any Granulicatella species is rare, with infection due to G. elegans rarer still. It is a Gram-positive bacteria that presents a diagnostic challenge due to non-specific symptoms at presentation and difficulty in growing the organism on culture medium. We present a case of G. elegans endocarditis in a young child, which illustrates the challenges in managing this condition and the importance of considering atypical organism endocarditis in children presenting with fever of unknown origin, in particular those with a background of congenital cardiac disease. We review the literature on Granulicatella endocarditis, and briefly discuss the challenges of managing this condition in a child with an autism spectrum disorder and learning difficulties.

Eight-year trends in the relative isolation frequency and antimicrobial susceptibility among bloodstream isolates from Greek hospitals: data from the Greek Electronic System for the Surveillance of Antimicrobial Resistance - WHONET-Greece, 2010 to 2017.

BackgroundAntimicrobial resistance (AMR) changes over time and continuous monitoring provides insight on trends to inform both empirical treatment and public health action.AimsTo survey trends in relative isolation frequency (RIF) and AMR among key bloodstream pathogens using data from the Greek Electronic System for the Surveillance of AMR (WHONET-Greece).MethodsThis observational study looked into routine susceptibility data of 50,488 blood culture isolates from hospitalised patients in 25 tertiary hospitals, participating in the WHONET-Greece for trends over time between January 2010 and December 2017. Only the first isolate per species from each patient was included. Hospital wards and intensive care units (ICUs) were analysed separately.ResultsDuring the study, the RIF of Acinetobacter baumannii increased in wards, as did the proportion of A. baumannii isolates, which were non-susceptibleto most antibiotics in both wards and ICUs. Coincidently, Klebsiella pneumoniae RIF declined while the respective rates of non-susceptible isolates to carbapenems and gentamicin increased. Pseudomonas aeruginosa RIF remained stable but decreasing proportions of non-susceptible isolates to all studied antibiotics, except imipenem were observed. Escherichia coli RIF increased as did the proportion of isolates non-susceptible to third-generation cephalosporins, carbapenems and fluoroquinolones. Concerning Staphylococcus aureus, a decline in the percentage of meticillin resistant isolates in ICUs was found, while the percentages of Enterococcus faecium isolates with non-susceptibility to vancomycin stayed stable.ConclusionsRecognising these trends over time is important, since the epidemiology of AMR is complex, involving different 'bug and drug' combinations. This should be taken into consideration to control AMR.

A nosocomial cluster of vancomycin resistant enterococci among COVID-19 patients in an intensive care unit.

BACKGROUND: Currently, hospitals have been forced to divert substantial resources to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic. It is unclear if this situation will affect long-standing infection prevention practices and impact on healthcare associated infections. Here, we report a nosocomial cluster of vancomycin-resistant enterococci (VRE) that occurred on a COVID-19 dedicated intensive care unit (ICU) despite intensified contact precautions during the current pandemic. Whole genome sequence-based typing (WGS) was used to investigate genetic relatedness of VRE isolates collected from COVID-19 and non-COVID-19 patients during the outbreak and to compare them to environmental VRE samples. METHODS: Five VRE isolated from patients (three clinical and two screening samples) as well as 11 VRE and six vancomycin susceptible Enterococcus faecium (E. faecium) samples from environmental sites underwent WGS during the outbreak investigation. Isolate relatedness was determined using core genome multilocus sequence typing (cgMLST). RESULTS: WGS revealed two genotypic distinct VRE clusters with genetically closely related patient and environmental isolates. The cluster was terminated by enhanced infection control bundle strategies. CONCLUSIONS: Our results illustrate the importance of continued adherence to infection prevention and control measures during the COVID-19 pandemic to prevent VRE transmission and healthcare associated infections.