Considerations About Antimicrobial Stewardship in Settings with Epidemic Extended-Spectrum β-Lactamase-Producing or Carbapenem-Resistant Enterobacteriaceae

Abstract

Infections caused by gram-negative bacteria (GNB) resistant to multiple classes of antibiotics are increasing in many hospitals. Extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae in particular are now endemic in many parts of the world and represent a serious public health threat. In this era, antimicrobial stewardship programs are essential as targeted and responsible use of antibiotics improves patient outcomes and hopefully limits the selective pressure that drives the further emergence of resistance. However, some stewardship strategies aimed at promoting carbapenem-sparing regimens remain controversial and are difficult to implement when resistance rates to non-carbapenem antibiotics are increasing. Coordinated efforts between stewardship programs and infection control are essential for reversing conditions that favor the emergence and dissemination of multidrug-resistant GNB within the hospital and identifying extra-institutional “feeder reservoirs” of resistant strains such as long-term care facilities, where colonization is common despite limited numbers of serious infections. In settings where ESBL resistance is endemic, the cost-effectiveness of expanded infection control efforts and antimicrobial stewardship is still unknown. Once a patient has been colonized, selective oral or digestive decontamination may be considered, but evidence supporting its effectiveness is limited in patients who are already colonized or in centers with high rates of resistance. Moreover, temporary success at decolonization may be associated with a higher risk of relapse with strains that are resistant to the decolonizing antibiotics.

Veterinarians’ Perception, Knowledge and Practices of Antibiotic Stewardship in Enugu State Southeast, Nigeria

“…The cost of developing a new antibiotic has been estimated to be US$1 billion (Huttner et al, 2013), but no new antibiotic is expected to be on the market until 2018 at the earliest (Bartlett, 2011;Cisneros et al, 2014). antibiotic use) is critical for ASPs to be successfully implemented (Cotta et al, 2014;Viale et al, 2015;Cabello et al, 2016). Thus, veterinarians (as clinicians and educators) play a critical role in ABS and for successful implementation of ASP (Bowater, 2015;Coyne et al, 2016).…”

What is the role of the new β-lactam/β-lactamase inhibitors ceftolozane/tazobactam and ceftazidime/avibactam?

“…We strongly recommend that these new drugs be used judiciously (e.g. within antimicrobial stewardship programs), taking into account the following factors for each clinical reality: the population of patients, the local bacterial epidemiology, and the risk of selecting pathogens resistant to the new BLBLI combinations because of their misuse [5,38]. We appeal to physicians not to 'waste' TOL/TAZ and CAZ/AVI by using them against non-MDR bacteria!…”

Risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections

“…Ureidopenicillins plus b-lactamase inhibitor can represent an alternative to carbapenems for specific treatment of infections due to microorganisms susceptible when MIC ≤2 mg/mL as well as for empiric treatment of urinary infections and nonsevere infections from other sites. [39][40] Before starting with empiric broad-spectrum antibiotic treatment, all in-patients suspected to have any infection, as well as outpatients admitted for severe infection, should perform a complete microbiological assessment (cultures of blood, urine and endotracheal aspiration if appropriate). The empiric treatment should be re-evaluated after 48 h and in the event that modified according to clinical response and microbiological results with de-escalation in the absence of resistant strains.…”

“…Viale et al recognized several risk factors predictive of a poor outcome: patient-related factors (age, comorbidities, APACHE score), infection-related factors (bloodstream or pulmonary source of infection, severe sepsis or septic shock, colistin-resistant strain) and treatment-related factors (not effective empiric treatment, monotherapy). 40 The lack of initially appropriate antibiotic therapy seems to be the major determinant of outcome in severe infections. In a recent series of 1076 patients with severe sepsis or septic shock due to Gram-negative pathogens, 5.9% of the isolates were MDR; overall in-hospital mortality was 29.2%.…”

“…Other drugs in clinical development are plazomicin (a novel aminoglycoside) and eravacycline (a new tetracycline), active against most KPC-producing Enterobacteriaceae. 40,41 Whenever available in microbiological laboratories, the new rapid molecular assays already licensed for commercial use, are of great utility to ensure an earlier effective treatment of MDR infections, and in particular of CRKP infections, with specific agents. The matrix-assisted laser desorption/ionization time of flight mass spectrometry is a fast and cost-effective test in which the mass-charge ratios of molecular fragments obtained by ionization and disintegration of a target molecule are compared with those of known microorganisms.…”