David E. Katz

The Continuing Plague of Extended-spectrum β-lactamase–producing Enterobacteriaceae Infections

Antimicrobial resistance is a common iatrogenic complication of modern life and medical care. One of the most demonstrative examples is the exponential increase in the incidence of extended-spectrum β-lactamases (ESBLs) production among Enterobacteriaceae, which is the most common human pathogens outside of the hospital settings. Infections resulting from ESBL-producing bacteria are associated with devastating outcomes, now affecting even previously healthy individuals. This development poses an enormous burden and threat to public health. This paper aims to narrate the evolving epidemiology of ESBL infections, and highlight current challenges in terms of management and prevention of these common infections.

The complex epidemiology of extended-spectrum β-lactamase-producing Enterobacteriaceae.

Antimicrobial resistance is a growing worldwide iatrogenic complication of modern medical care. Extended-spectrum β-lactamases have emerged as one of the most successful resistance mechanisms, limiting our therapeutic options to treat various human infections. The dissemination of these enzymes to the community probably signifies an irreversible step. This paper will review the evolution of human infections associated with extended-spectrum β-lactamase-producing organisms in the past 20 years, and will present and discuss the current challenges, controversies, debates and knowledge gaps in this research field.

American Geriatrics Society Position Statement on Feeding Tubes in Advanced Dementia

To the Editor: We agree with the American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee in that careful hand feeding should be offered to all individuals with advanced dementia. However, people with dementia must have a feeding tube placed under certain circumstances (e.g., beliefs, family burdens, family-related responsibilities, nursing home characteristics, acute hospital settings). Sometimes, surprisingly, the main and only indication for placing a feeding tube is prevention of aspiration pneumonia. Taking this into consideration those circumstances, we disagree that difficulty eating and feeding is associated with poor prognosis over the short term. Although the short-term prognosis, accurate prognosis of survival in advanced dementia is elusive. In addition, the assertion that tube feeding is associated with agitation and greater use of physical and chemical restraints is not completely correct. The setting might be completely different for individuals with dementia with a nasoenteric tube and those with percutaneous gastrostomy (PEG). In the case of nasoenteric tube, behavioral disturbances appear in many individuals and it is therefore necessary to prescribe physical or chemical (e.g., neuroleptics, benzodiazepines) restraints. In a previous letter to this journal, we reported that individuals with advanced dementia and PEG tubes did not exhibit PEG-associated behavioral disturbances and did not need any physical or chemical restrain. Although advanced dementia is a serious burden for health systems, professionals, relatives, and the individuals themselves we must be aware of some opinions on this topic. The individual’s comfort must be the main goal, but is an untreated individual with pneumonia, fever, or eating problems comfortable? Finally, advanced dementia is usually a complicated condition with a long trajectory. To affirm that all individuals with dementia have a terminal illness and therefore that use of a PEG tube must be completely excluded in elderly adults with dementia is similar to the idea described in a famous children’s story: “Sentence first—verdict afterwards.”

Escherichia coli, cattle, and the propagation of disease.

Abstract Several early models describing host‐pathogen interaction have assumed that each individual host has approximately the same likelihood of becoming infected or of infecting others. More recently, a concept that has been increasingly emphasized in many studies is that for many infectious diseases, transmission is not homogeneous but highly skewed at the level of populations. In what became known as the ‘20/80 rule’, about 20% of the hosts in a population were found to contribute to about 80% of the transmission potential. These heterogeneities have been described for the interaction between many microorganisms and their human or animal hosts. Several epidemiological studies have reported transmission heterogeneities for Escherichia coli by cattle, a phenomenon with far‐reaching agricultural, medical and public health implications. Focusing on E. coli as a case study, this paper will describe super‐spreading and super‐shedding by cattle, review the main factors that shape these transmission heterogeneities and examine the interface with human health. Escherichia coli super‐shedding and super‐spreading by cattle are shaped by microorganism‐specific, cattle‐specific and environmental factors. Understanding the factors that shape heterogeneities in E. coli dispersion by cattle and the implications for human health represent key components that are critical for targeted infection control initiatives.

Emergence and Control of Antibiotic-resistant Gram-negative Bacilli in Older Adults

The prevalence of multidrug resistant Gram-negative organisms is increasing worldwide. The Infectious Diseases Society of America has previously singled out groups of pathogens with the highest threat, the majority of which are Gram-negative bacilli. These isolates are prevalent not only in intensive-care units of acute-care facilities, but are also found among residents of long-term care facilities with various levels of care, and occasionally among patients without exposure to healthcare systems. Advanced age is an independent predictor for carriage of many of these organisms, and elderly patients are subjected to worse outcomes following the acquisition of resistant Gram-negatives. Due to their frequent admissions and transfers across different healthcare facilities within a region, the elderly constitute important epidemiological reservoirs for these bacteria. Containing the acquisitions of resistant Gram-negatives among the elderly could be achieved through reduction of either 1) selective pressure (e.g. less antibiotics) or 2) colonization pressure (e.g. less exposure to resistant bacteria). This manuscript will review the present situation of multidrug resistant Gram-negative organisms, especially among the elderly, and the infection control interventions that might mitigate their further spread.

Diabetic foot infection in hospitalized adults

BACKGROUNDnAcute infections of the diabetic foot (DFI) are a common and complex condition. Patients are generally managed in the ambulatory setting and epidemiological data pertaining to hospitalized patients is lacking. The aim of this study was to analyze the epidemiology, microbiology and outcomes of hospitalized patients with DFI, who are managed at a referral center equipped with hyperbaric oxygen (HBO) therapy.nnnMETHODSnA retrospective cohort study of adult patients admitted to a tertiary referral center with DFI over a six-month period in 2013 was undertaken. Predictors of clinical outcomes and efficacy of treatment modalities were analyzed by Cox regression.nnnRESULTSnSixty-one patients with DFI were identified. Most patients were elderly (67xa0±xa013 years), with long-standing (17xa0±xa09 years), poorly controlled (HbA1c 9xa0±xa03%) diabetes. Most patients had polymicrobial infection (80%); specifically, anaerobic (39%) and multi or extensively-drug resistant organisms (61%). Administration of appropriate antimicrobials was delayed for >48xa0h in 83%. Advanced age was associated with worse outcomes. Sicker patients with severe peripheral vascular disease were managed with HBO. The use of HBO was associated with higher costs and increased functional deterioration, and did not prevent future limb amputation.nnnCONCLUSIONSnOur study illustrates the descriptive epidemiology of hospitalized adults with DFI predominantly of polymicrobial etiology. MDROs and anaerobic organisms are common causative pathogens, and appropriate antibiotics were frequently delayed. HBO treatment may delay the need for limb amputation, but not obviate this eventual outcome.

Multidrug-Resistant Gram-Negative Bacilli: Infection Prevention Considerations

Antimicrobial resistance is a common iatrogenic complication of modern healthcare. Gram-negative organisms pose the biggest challenge to healthcare today, predominantly due to lack of effective therapeutic options. Containing the spread of these organisms is challenging, and in reality, the application of multiple control measures during an evolving outbreak or while high endemic rates are recorded makes it difficult to measure the relative impact of each measure. This chapter will review the utility of various infection control measures in containing the spread of multidrug-resistant Gram-negative bacilli.

Therapeutic Management of Pseudomonas aeruginosa Bloodstream Infection Non-Susceptible to Carbapenems but Susceptible to “Old” Cephalosporins and/or to Penicillins

It is unknown as to whether other beta-lactams can be used for bloodstream infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non-susceptible to one or more carbapenem. We conducted a retrospective cohort study at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014. Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but susceptible to ceftazidime or piperacillin (with or without tazobactam), were enrolled. We compared the outcomes of patients who received an appropriate beta-lactam antibiotic (“cases”) to those who received an appropriate non-beta-lactam antibiotic (“controls”). Whole genome sequencing was performed for one of the isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and one colistin and an aminoglycoside). All clinical outcomes were similar between the groups. There were large variations in the phenotypic susceptibilities of the strains. A detailed molecular investigation of one isolate revealed a strain that belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene was intact. Non-carbapenem-β-lactams may still be effective alternatives for short duration therapy (up to 14 days) for BSI caused by a carbapenem non-susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin-tazobactam) PA strain. This observation requires further confirmatory analyses. Future molecular investigations should be performed, in order to further analyze additional potential mechanisms for this prevalent phenotype.

The epidemiological impact and significance of carbapenem resistance in Pseudomonas aeruginosa bloodstream infections: a matched case–case-control analysis

A case-case-control investigation (N = 255 patients) explored the epidemiology of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Recent exposure to carbapenems and a rapidly fatal condition should prompt practitioners to shorten delays in initiating appropriate therapy, which can adversely impact CRPA outcomes, as opposed to the isolated impact of the carbapenem resistance determinant.

Antibiotic Resistance of Non-pneumococcal Streptococci and Its Clinical Impact

The taxonomy of streptococci has undergone major changes during the last two decades. The present classification is based on both phenotypic and genotypic data. Phylogenetic classification of streptococci is based on 16S rRNA sequences [1], and it forms the backbone of the overall classification system of streptococci. Phenotypic properties are also important, especially for clinical microbiologists. The type of hemolysis on blood agar, reaction with Lancefield grouping antisera, resistance to optochin, and bile solubility remain important for grouping of clinical Streptococcus isolates and therefore treatment options [2]. In the following chapter, two phenotypic classification groups, viridans group streptococci (VGS) and beta-hemolytic streptococci, will be discussed.