Pharmacokinetic and Pharmacodynamic Considerations of Antibiotics of Last Resort in Treating Gram-Negative Infections in Adult Critically Ill Patients

Heavner, Mojdeh; Claeys, Kimberly C; Masich, Anne M.; Gonzales, Jeffrey

doi:10.1007/s11908-018-0614-0

Cited by 10 publications

(5 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Extended-spectrum β-lactam (ESBL) resistant E. coli are of particular public health concern [ 19 ] as they are able to inactivate most β-lactam antimicrobials [ 20 ] used to treat associated infections. Presently, ESBL bacteria are a common source of therapeutic failure due to frequent co-resistance to multiple last resort antimicrobials [ 21 , 22 ] including colistin (i.e., polymyxin E), aminoglycoside, and 3rd and 4th generation cephalosporins that are used to treat a significant proportion of nosocomial infections [ 23 , 24 , 25 ]. In veterinary and human medicine, the extended-spectrum cephalosporins which are a sub-class of ESBL are regarded as critically important [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

A One Health Comparative Assessment of Antimicrobial Resistance in Generic and Extended-Spectrum Cephalosporin-Resistant Escherichia coli from Beef Production, Sewage and Clinical Settings

et al. 2020

View full text Add to dashboard Cite

This study aimed to compare antimicrobial resistance (AMR) in extended-spectrum cephalosporin-resistant and generic Escherichia coli from a One Health continuum of the beef production system in Alberta, Canada. A total of 705 extended-spectrum cephalosporin-resistant E. coli (ESCr) were obtained from: cattle feces (CFeces, n = 382), catch basins (CBasins, n = 137), surrounding streams (SStreams, n = 59), beef processing plants (BProcessing, n = 4), municipal sewage (MSewage; n = 98) and human clinical specimens (CHumans, n = 25). Generic isolates (663) included: CFeces (n = 142), CBasins (n = 185), SStreams (n = 81), BProcessing (n = 159) and MSewage (n = 96). All isolates were screened for antimicrobial susceptibility to 9 antimicrobials and two clavulanic acid combinations. In ESCr, oxytetracycline (87.7%), ampicillin (84.4%) and streptomycin (73.8%) resistance phenotypes were the most common, with source influencing AMR prevalence (p < 0.001). In generic E. coli, oxytetracycline (51.1%), streptomycin (22.6%), ampicillin (22.5%) and sulfisoxazole (14.3%) resistance were most common. Overall, 88.8% of ESCr, and 26.7% of generic isolates exhibited multi-drug resistance (MDR). MDR in ESCr was high from all sources: CFeces (97.1%), MSewage (96.9%), CHumans (96%), BProcessing (100%), CBasins (70.5%) and SStreams (61.4%). MDR in generic E. coli was lower with CFeces (45.1%), CBasins (34.6%), SStreams (23.5%), MSewage (13.6%) and BProcessing (10.7%). ESBL phenotypes were confirmed in 24.7% (n = 174) ESCr and 0.6% of generic E. coli. Prevalence of bla genes in ESCr were blaCTXM (30.1%), blaCTXM-1 (21.6%), blaTEM (20%), blaCTXM-9 (7.9%), blaOXA (3.0%), blaCTXM-2 (6.4%), blaSHV (1.4%) and AmpC β-lactamase blaCMY (81.3%). The lower AMR in ESCr from SStreams and BProcessing and higher AMR in CHumans and CFeces likely reflects antimicrobial use in these environments. Although MDR levels were higher in ESCr as compared to generic E. coli, AMR to the same antimicrobials ranked high in both ESCr and generic E. coli sub-populations. This suggests that both sub-populations reflect similar AMR trends and are equally useful for AMR surveillance. Considering that MDR ESCr MSewage isolates were obtained without enrichment, while those from CFeces were obtained with enrichment, MSewage may serve as a hot spot for MDR emergence and dissemination.

show abstract

Section: Introductionmentioning

confidence: 99%

A One Health Comparative Assessment of Antimicrobial Resistance in Generic and Extended-Spectrum Cephalosporin-Resistant Escherichia coli from Beef Production, Sewage and Clinical Settings

et al. 2020

View full text Add to dashboard Cite

show abstract

“…baumanni [ 62 ]. Doses higher than those recommended (100 mg bid) are necessary for clinical cure and possibly to prevent resistance development [ 63 ].…”

Section: Pk/pd Issues and Antimicrobial Resistancementioning

confidence: 99%

Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting—Focus on ICU Patients and Gram-Negative Strains

2020

View full text Add to dashboard Cite

The containment of the phenomenon of resistance towards antimicrobials is a priority, especially in preserving molecules acting against Gram-negative pathogens, which represent the isolates more frequently found in the fragile population of patients admitted to Intensive Care Units. Antimicrobial therapy aims to prevent resistance through several actions, which are collectively known as “antimicrobial stewardship”, to be taken together, including the application of pharmacokinetic/pharmacodynamic (PK/PD) principles. PK/PD application has been shown to prevent the emergence of resistance in numerous experimental studies, although a straight translation to the clinical setting is not possible. Individualized antibiotic dosing and duration should be pursued in all patients, and even more especially when treating intensive care unit (ICU) septic patients in whom optimal exposure is both difficult to achieve and necessary. In this review, we report on the available data that support the application of PK/PD parameters to contain the development of resistance and we give some practical suggestions that can help to translate the benefit of PK/PD application to the bedside.

show abstract

“…In patients who are at greater risk of MDR bacteria empiric therapy needs to cover these organisms, often including Pseudomonas and methicillin resistant Staphylococcus aureus (MRSA). These two organisms in particular pose a problem as they are frequently resistant to most frontline antibiotics, and their treatment can involve antibiotics such as aminoglycosides and glycopeptides, which have an unfavourable toxicity profile (110). Empiric therapy runs the risk of over-treatment and thus increases the risk of toxic side effects.…”

Section: Management Of Pneumonia In Icuantimicrobialsmentioning

confidence: 99%

Management of pneumonia in intensive care

Morris¹

2018

J Emerg Crit Care Med

View full text Add to dashboard Cite

Pneumonia, an inflammatory infiltrate of the alveolar airspace, is commonly triggered by bacterial infection of the lungs, or less commonly by viral or fungal infection. It remains the commonest infective reason for admission to intensive care as well as being the most common secondary infection acquired whilst in the intensive care unit (ICU). It presents a significant global burden of disease and is especially prevalent in low-and middle-income countries. The major categories of pneumonia encountered by the Intensive Care clinician are community-acquired, ventilator-acquired, non-ventilator hospitalacquired and pneumonia in the immunocompromised patient. An appreciation of the type of pneumonia a patient has developed is critical to its effective treatment. Pneumonia is the commonest precipitant of acute respiratory distress syndrome (ARDS) and clinicians should be mindful that the evidence-base surrounding ARDS will, in large part, apply to severe pneumonia. The causative organisms which lead to pneumonia vary depending on the site of acquisition (community or hospital-acquired), the immune status of the patient and the presence of intercurrent medications including antibiotics. Current standard microbiological testing is seldom able to give a rapid answer as to which microorganisms is present and causing infection. Therefore, empirical therapy guided by knowledge of local microbial flora and resistance patterns is the recommended course of action. This approach risks the over-treatment of pneumonia with unnecessarily broad-spectrum agents which bring with them the problems of antibiotic-associated harm. Novel rapid diagnostic tests aimed at both the pathogen and the host response hold promise in the rationalisation and appropriate targeting of antimicrobial therapy. At present neither scoring systems nor diagnostic tests are able to accurately risk stratify a patient's need for intensive care admission. Beyond antibiotic therapy, a number of adjuvant therapies have been trialled in pneumonia although none have yet made it into widespread clinical use. Corticosteroids are recommended in some cases of community-acquired pneumonia (CAP), but their role in the patient with severe CAP in ICU remains uncertain whilst they are a risk factor for the development of hospital and ventilator-acquired pneumonia. Immuno-stimulation has not yet translated from small scale clinical trials into clinical use. Supportive management includes lung protective ventilation, and those interventions proven to improve outcomes in ARDS. This review will give an overview of the epidemiology of severe pneumonia, the microbiological causes and diagnostic strategies. It will then turn to management, including antimicrobial therapy, role of adjuvant therapies, respiratory support and prevention of complications.

show abstract

Pharmacokinetic and Pharmacodynamic Considerations of Antibiotics of Last Resort in Treating Gram-Negative Infections in Adult Critically Ill Patients

Cited by 10 publications

References 99 publications

A One Health Comparative Assessment of Antimicrobial Resistance in Generic and Extended-Spectrum Cephalosporin-Resistant Escherichia coli from Beef Production, Sewage and Clinical Settings

A One Health Comparative Assessment of Antimicrobial Resistance in Generic and Extended-Spectrum Cephalosporin-Resistant Escherichia coli from Beef Production, Sewage and Clinical Settings

Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting—Focus on ICU Patients and Gram-Negative Strains

Management of pneumonia in intensive care

Contact Info

Product

Resources

About