Hospital Ward Antibiotic Prescribing and the Risks of<i>Clostridium difficile</i>Infection

Brown, Kevin A.; Valenta, Kim; Fisman, David N.; Simor, Andrew E.; Daneman, Nick

doi:10.1001/jamainternmed.2014.8273

Cited by 111 publications

(91 citation statements)

References 26 publications

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“…Broad-spectrum antibiotics disrupt the gut microbiome and encourage infection with Clostridium difficile , a growing health problem as a complication following antibiotic therapy. 60 …”

Section: Discussionmentioning

confidence: 99%

Immucillins in Infectious Diseases

2017

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The Immucillins are chemically stable analogues that mimic the ribocation and leaving-group features of N-ribosyltransferase transition states. Infectious disease agents often rely on ribosyltransferase chemistry in pathways involving precursor synthesis for nucleic acids, salvage of nucleic acid precursors, or synthetic pathways with nucleoside intermediates. Here, we review three infectious agents and the use of the Immucillins to taget enzymes essential to the parasites. First, DADMe-Immucillin-G is a purine nucleoside phosphorylase (PNP) inhibitor that blocks purine salvage and shows clinical potential for treatment for the malaria parasite Plasmodium falciparum, a purine auxotroph requiring hypoxanthine for purine nucleotide synthesis. Inhibition of the PNPs in the host and in parasite cells leads to apurinic starvation and death. Second, Helicobacter pylori, a causative agent of human ulcers, synthesizes menaquinone, an essential electron transfer agent, in a pathway requiring aminofutalosine nucleoside hydrolysis. Inhibitors of the H. pylori methylthioadenosine nucleosidase (MTAN) are powerful antibiotics for this organism. Synthesis of menaquinone by the aminofutalosine pathway does not occur in most bacteria populating the human gut microbiome. Thus, MTAN inhibitors provide high-specificity antibiotics for H. pylori and are not expected to disrupt the normal gut bacterial flora. Third, Immucillin-A was designed as a transition state analogue of the atypical PNP from Trichomonas vaginalis. In antiviral screens, Immucillin-A was shown to act as a prodrug. It is active against filoviruses and flaviviruses. In virus-infected cells, Immucillin-A is converted to the triphosphate, is incorporated into the viral transcript, and functions as an atypical chain-terminator for RNA-dependent RNA polymerases. Immucillin-A has entered clinical trials for use as an antiviral. We also summarize other Immucillins that have been characterized in successful clinical trials for T-cell lymphoma and gout. The human trials support the potential development of the Immucillins in infectious diseases.

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“…Broad-spectrum antibiotics disrupt the gut microbiome and encourage infection with Clostridium difficile , a growing health problem as a complication following antibiotic therapy. 60 …”

Section: Discussionmentioning

confidence: 99%

Immucillins in Infectious Diseases

2017

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“…For example, the risk for CDI is associated with the quantity of antibiotics used on a particular unit. 34 Unfortunately, we are unable to control for hospital-level antibiotic use directly because the family of Healthcare Cost and Utilization Project SIDs does not contain antibiotic prescribing. Therefore, we cannot rule out that a hospital’s CDI rate is a surrogate marker for patterns of excessive antibiotic use.…”

Section: Discussionmentioning

confidence: 99%

Hospital Clostridium difficile infection (CDI) incidence as a risk factor for hospital-associated CDI

Polgreen

Cavanaugh

Polgreen

2016

American Journal of Infection Control

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Background Environmental risk factors for Clostridium difficile infections (CDIs) have been described at the room or unit level but not the hospital level. To understand the environmental risk factors for CDI, we investigated the association between institutional- and individual-level CDI. Methods We performed a retrospective cohort study using the Healthcare Cost and Utilization Project state inpatient databases for California (2005–2011). For each patient’s hospital stay, we calculated the hospital CDI incidence rate corresponding to the patient’s quarter of discharge, while excluding each patient’s own CDI status. Adjusting for patient and hospital characteristics, we ran a pooled logistic regression to determine individual CDI risk attributable to the hospital’s CDI rate. Results There were 10,329,988 patients (26,086 cases and 10,303,902 noncases) who were analyzed. We found that a percentage point increase in the CDI incidence rate a patient encountered increased the odds of CDI by a factor of 1.182. Conclusions As a point of comparison, a 1-percentage point increase in the CDI incidence rate that the patient encountered had roughly the same impact on their odds of acquiring CDI as a 55.8-day increase in their length of stay or a 60-year increase in age. Patients treated in hospitals with a higher CDI rate are more likely to acquire CDI.

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“…The hazards of antibiotic use may extend beyond the individual patient. As ward-level antibiotic use increases, so too does an individual patient’s risk of C. difficile infection, even when he or she has not directly received antibiotics 2. In this study, Freedberg et al aim to provide perhaps the most direct evidence of the indirect hazards of antibiotic use on the risk of C. difficile —by testing whether antibiotic receipt by a hospital bed occupant increases the risk of C. difficile for the next bed occupant.…”

Section: Contextmentioning

confidence: 99%

Hospital Ward Antibiotic Prescribing and the Risks ofClostridium difficileInfection

Cited by 111 publications

References 26 publications

Immucillins in Infectious Diseases

Immucillins in Infectious Diseases

Hospital Clostridium difficile infection (CDI) incidence as a risk factor for hospital-associated CDI

Prescribing antibiotics to hospitalised patients increases the risk ofClostridium difficileinfection for the next bed occupant

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