scholarly journals Asymmetric Effects of Decontamination Using Topical Antibiotics for the ICU Patient

Symmetry ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1027
Author(s):  
James C. Hurley
Keyword(s):  
Infection Prevention ◽  
Natural Experiment ◽  
Antibiotic Use ◽  
Ventilator Associated Pneumonia ◽  
Control Groups ◽  
Topical Antibiotic ◽  
Topical Antibiotics ◽  
Concurrent Control ◽  
Asymmetric Effects ◽  
Prevention Studies

There are several antiseptic, antibiotic and non-decontamination-based interventions for preventing intensive care unit (ICU) acquired infection. These have been evaluated in >200 studies. Infection prevention using topical antibiotic prophylaxis (TAP) appears to be the most effective. Whether antibiotic use in the ICU may influence the risk of infection among concurrent control patients within the same ICU and result in asymmetrical herd effects cannot be resolved with individual studies examined in isolation. The collective observations within control and intervention groups from numerous ICU infection prevention studies simulates a multi-center natural experiment enabling the herd effects of antibiotics to be evaluated. Among the TAP control groups, the incidences for both ventilator associated pneumonia (VAP) and mortality are unusually high in comparison to literature-derived benchmarks. Paradoxically, amongst the TAP intervention groups, the incidences of mortality are also unusually high and the VAP incidences are similar (i.e., not lower) compared to the incidences among studies of other interventions. By contrast, the mortality incidences among the intervention groups of other studies are similar to those among the intervention groups of TAP studies. Using topical antibiotics to prevent infections acquired within the ICU environment may result in profoundly asymmetrical effects.

scholarly journals 127Topical antibiotics used to prevent infection in the ICU: an accidental natural herd exposure experiment

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
James Hurley
Keyword(s):  
Systematic Reviews ◽  
Infection Prevention ◽  
Intervention Group ◽  
Control Group ◽  
Control Groups ◽  
Topical Antibiotic ◽  
Herd Effect ◽  
Icu Patients ◽  
Topical Antibiotics ◽  
Prevention Methods

Abstract Background Multiple studies of topical antibiotics applied to ICU patients appear to show potent infection prevention effects versus studies of other interventions. However, the effect is less apparent for studies using non-concurrent (NCC) versus concurrent controls (CC) implying the possibility of a herd effect. Methods 206 studies of infection prevention among ICU patients, sourced from 15 systematic reviews were stratified into those using topical antibiotics with NCC versus with CC versus studies of other prevention methods. The event rates were summarised using generalized estimating equations and compared to other studies without an intervention (literature benchmark). Results The summary effect sizes for pneumonia and mortality prevention derived in the systematic reviews were replicated. The mean ICU mortality incidence for topical antibiotic study CC control groups (28.5%; 95% CI, 25.0-32.3; n = 41) is higher versus a literature benchmark (23.7%; 19.2%-28.5%; n = 34), versus NCC control groups (23.5%; 19.3-28.3; n = 14) and versus topical antibiotic intervention groups (24.4%; 22.1 – 26.9; n = 62). In meta-regression models adjusted for group mean age and publication year, CC group membership within a topical antibiotic study remains associated with higher mortality (p = 0.027). Conclusions Within topical antibiotic studies, the CC control group mortality incidences are inexplicably high, whereas the intervention group incidences are paradoxically similar to a literature-derived benchmark. Key messages An adverse herd effect is apparent for topical antibiotics used to prevent infection among ICU patients.

scholarly journals Topical Antibiotic Use Coselects for the Carriage of Mobile Genetic Elements Conferring Resistance to Unrelated Antimicrobials in Staphylococcus aureus

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Glen P. Carter ◽  
Mark B. Schultz ◽  
Sarah L. Baines ◽  
Anders Gonçalves da Silva ◽  
Helen Heffernan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
New Zealand ◽  
Single Molecule ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Topical Antibiotic ◽  
Content Type ◽  
Topical Antibiotics ◽  
The Impact

ABSTRACTTopical antibiotics, such as mupirocin and fusidic acid, are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, the widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains. New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences single-molecule real-time (SMRT) whole-genome sequencing, Illumina short-read sequencing, and Bayesian phylogenomic modeling on 118 new multilocus sequence type 1 (ST1) communityStaphylococcus aureusisolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1S. aureus. We also providein vitroexperimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDRS. aureusisolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.

scholarly journals Structural equation modelling the ‘control of gut overgrowth’ in the prevention of ICU acquired Gram-negative infection.

2020 ◽  
Author(s):  
James C Hurley
Keyword(s):  
Latent Variables ◽  
Structural Equation ◽  
Infection Prevention ◽  
Structural Equation Models ◽  
Control Groups ◽  
Parenteral Antibiotic ◽  
Gram Negative ◽  
Positive Effects ◽  
Prevention Studies ◽  
Negative Effect

Abstract Background: Conceptually, the ‘control of gut overgrowth’ (COGO) is key to the mediation of infection prevention with ‘abnormal Gram-negative bacilli’ (AGNB) by Selective Digestive Decontamination (SDD). However, the relative importance of the SDD components; topical (TAP), enteral (EAP) and protocolized parenteral antibiotic prophylaxis (PPAP), versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies. Methods: Seven candidate generalized structural equation models (GSEM) founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator associated pneumonia (VAP) data derived from >200 infection prevention studies. The following group level exposures were included in the GSEM models; use of TAP, EAP, PPAP, antiseptic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation (MV); trauma ICU; mean length of ICU stay and concurrency versus non-concurrency of TAP study control groups. Results: In GSEM modelling of Pseudomonas and Acinetobacter gut overgrowth (GO) as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas GO but no intervention was significantly negative against Acinetobacter GO. Strikingly, PPAP and concurrency each have positive effects in the model, EAP is neutral and Acinetobacter bacteremia incidences are high within TAP studies, moreso with PPAP exposure. Paradoxically, TAP (moreso with PPAP) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP. Conclusions: GSEM modelling of published AGNB infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of TAP.

scholarly journals The role of preventive topical antibiotic treatment prior to intravitreal injection

2015 ◽  
Vol 8 (2) ◽  
pp. 79-83 ◽  
Author(s):  
Elena Vladimirovna Ageeva ◽  
Anna Evgen'yevna Grodnenskaya ◽  
Kseniya Aleksandrovna Popova
Keyword(s):  
Macular Degeneration ◽  
Intravitreal Injection ◽  
Staphylococcus Epidermidis ◽  
Povidone Iodine ◽  
Antibiotic Use ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Topical Antibiotic ◽  
Topical Antibiotics ◽  
Age Related

Treatment of wet age-related macular degeneration (AMD) requires frequent intravitreal injections of anti-VEGF agents, sometimes on monthly basis during a long period of time. Endophthalmitis is a rare but extremely severe complication of intravitreal injections. As it has been proven before, the flora from the conjunctival surface is the main source for endophthalmitis. Using Povidone-iodine solution (Betadine10 % Povidone-iodine, EGIS PHARMACEUTICALS) is the only way to prevent endophthalmitis. The efficacy of it was proven by numerous studies. No evidence exists that topical antibiotiotics prior and after injections could be effective for prevention of endophthalmitis. Purpose: To study the advisability of topical antibiotic application before intravitreal injection. Materials and methods: Under investigation, there were 25 eyes of 25 patients with wet AMD treated by anti-VEGF intravitreal injections. All patients used topical antibiotics 3 days before injection. Conjunctival culture from injection eye was collected three times: before topical antibiotic use; after topical antibiotic use, and after Betadine 5 % application. Results: The rates of Staphylococcus epidermidis before and after topical antibiotic use were approximately equal. However there was no Staphylococcus epidermidis found after Betadine 5 % application. Conclusion: Our study showed the effectiveness of Betadine 5 % solution in conjunctival flora reduction. Use of topical antibiotics 3 days prior intravitreal injections is not effective. Key words: age-related macular degeneration; endophthalmitis; intravitreal injection; topical antibiotics; endophthalmitis prevention.

scholarly journals Clinical relevance of topical antibiotic use in co-selecting for multidrug-resistant Staphylococcus aureus: Insights from in vitro and ex vivo models

2021 ◽  
Author(s):  
Yi Nong ◽  
George Taiaroa ◽  
Shivani Pasricha ◽  
Romain Guérillot ◽  
Ian R Monk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Targeted Mutagenesis ◽  
Topical Antibiotic ◽  
Experimental Proof ◽  
Topical Antibiotics ◽  
Superficial Skin

Topical antibiotic preparations, such as fusidic acid (FA) or mupirocin, are used in the prevention and treatment of superficial skin infections caused by staphylococci. Previous genomic epidemiology work has suggested an association between the widespread use of topical antibiotics and the emergence of methicillin resistant Staphylococcus aureus in some settings. In this study, we provide experimental proof of co-selection for multidrug resistance in S. aureus following exposure to FA or mupirocin. Through targeted mutagenesis and phenotypic analyses, we confirmed that fusC carriage confers resistance to FA, and mupA carriage confers high-level resistance to mupirocin in multiple S. aureus genetic backgrounds. In vitro experiments demonstrated that carriage of fusC and mupA confer a competitive advantage in the presence of sub-inhibitory concentrations of FA and mupirocin, respectively. Further, we used a porcine skin colonisation model to show that clinically relevant concentrations of topical antibiotics can co-select for presence of unrelated antimicrobial resistance determinants, such as mecA, blaZ, and qacA, in fusC or mupA harbouring S. aureus. These findings provide valuable insights on the role of acquired FA or mupirocin resistance in co-selecting for broader antibiotic resistance in S. aureus, prompting greater need for judicious use of topical antibiotics.

scholarly journals 128Study data within systematic reviews of intensive care interventions analysed as a cluster randomized trial

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
James Hurley
Keyword(s):  
Systematic Reviews ◽  
Prolonged Mechanical Ventilation ◽  
Intervention Group ◽  
Population Level ◽  
Cluster Randomized Trial ◽  
Contextual Effect ◽  
Control Groups ◽  
Topical Antibiotics ◽  
Concurrent Control ◽  
Cluster Randomized

Abstract Focus of Presentation Cluster randomized trials (CRT) can address infectious disease research questions at the whole-of-population level, such as herd protection and herd peril effects, that cannot be answered within randomized controlled trials. For adequate power, ideally, a CRT will have at least 40 clusters. Findings Studies of decontamination (using either chlorhexidine or topical antibiotics) to prevent ICU-acquired infections among adult patients requiring prolonged mechanical ventilation (MV) have been summarized in > 15 systematic reviews. Of 83 studies of topical antibiotics, 69 had concurrent control (CC) versus non-concurrent control (NCC; n = 14) design (Figure below; solid symbols are intervention group patients). The mean ICU pneumonia incidence for topical antibiotic study CC control groups (34.5%; 95% CI, 29.1-40.4) is higher versus a literature benchmark (26.1%; 23.3%-29.1%), and versus NCC control groups (29.9%; 21.4-40.4) and versus chlorhexidine study CC control groups (25.5%; 19.6 – 32.5; n = 17). Conclusions/Implications Benchmarking the event rates among control groups versus the event rate among non-intervention studies for MV patients provide a measure of the contextual effect of the intervention. Differing intervention effects for studies with CC versus NCC design implicates herd effects. Key messages Systematic reviews of interventions that include studies with CC versus NCC design provide a natural experiment of contextual effects where their study otherwise would be difficult or, for adverse herd effects, unethical.

Inapparent Outbreaks of Ventilator-Associated Pneumonia An Ecologic Analysis of Prevention and Cohort Studies

2005 ◽  
Vol 26 (4) ◽  
pp. 374-390 ◽  
Author(s):  
James C. Hurley
Keyword(s):  
Cohort Study ◽  
Regression Models ◽  
Study Groups ◽  
Cross Infection ◽  
Ventilator Associated Pneumonia ◽  
Reference Standard ◽  
Control Groups ◽  
Prevention Studies ◽  
Cohort Groups ◽  
Linear Regressions

AbstractObjective:To compare ventilator-associated pneumonia (VAP) rates and patterns of isolates across studies of antibiotic and non-antibiotic methods for preventing VAP.Design:With the use of 42 cohort study groups as the reference standard, the prevalence of VAP was modeled in two linear regressions: one with the control groups and the other with the intervention groups of 96 VAP prevention studies. The proportion of patients admitted with trauma and the VAP diagnostic criteria were used as ecologic correlates. Also, the patterns of pathogenic isolates were available for 117 groups.Results:In the first regression model, the VAP rates for the control groups of antibiotic-based prevention studies were at least 18 (CI95, 12 to 24) per 100 patients higher than those in the cohort study groups (P< .001). By contrast, comparisons of cohort study groups with all other control and intervention groups in the first and second regression models yielded differences that were less than 6 per 100 and not significant (P> .05). For control groups with VAP rates greater than 35%, the patterns of VAP isolates, such as the proportion ofStaphylococcus aureus,more closely resembled those in the corresponding intervention groups than in the cohort groups.Conclusions:The rates of VAP in the control groups of the antibiotic prevention studies were significantly higher than expected and the patterns of pathogenic isolates were unusual. These observations suggest that inapparent outbreaks of VAP occurred in these studies. The possibility remains that antibiotic-based VAP prevention presents a major cross-infection hazard.

scholarly journals Candida–Acinetobacter–Pseudomonas Interaction Modelled within 286 ICU Infection Prevention Studies

2020 ◽  
Vol 6 (4) ◽  
pp. 252
Author(s):  
James C. Hurley
Keyword(s):  
Antibiotic Prophylaxis ◽  
Latent Variables ◽  
Structural Equation ◽  
Infection Prevention ◽  
Structural Equation Models ◽  
Candida Colonization ◽  
Topical Antibiotic ◽  
Effective Prevention ◽  
Prevention Studies ◽  
Improved Model

Background: Whether Candida interacts to enhance the invasive potential of Acinetobacter and Pseudomonas bacteria cannot be resolved within individual studies. There are several anti-septic, antibiotic, anti-fungal, and non-decontamination-based interventions to prevent ICU acquired infection. These effective prevention interventions would be expected to variably impact Candida colonization. The collective observations within control and intervention groups from numerous ICU infection prevention studies simulates a multi-centre natural experiment with which to evaluate Candida, Acinetobacter and Pseudomonas interaction (CAPI). Methods: Eight Candidate-generalized structural equation models (GSEM), with Candida, Pseudomonas and Acinetobacter colonization as latent variables, were confronted with blood culture and respiratory tract isolate data derived from >400 groups derived from 286 infection prevention studies. Results: Introducing an interaction term between Candida colonization and each of Pseudomonas and Acinetobacter colonization improved model fit in each case. The size of the coefficients (and 95% confidence intervals) for these interaction terms in the optimal Pseudomonas (+0.33; 0.22 to 0.45) and Acinetobacter models (+0.32; 0.01 to 0.5) were similar to each other and similar in magnitude, but contrary in direction, to the coefficient for exposure to topical antibiotic prophylaxis (TAP) on Pseudomonas colonization (−0.45; −0.71 to −0.2). The coefficient for exposure to topical antibiotic prophylaxis on Acinetobacter colonization was not significant. Conclusions: GSEM modelling of published ICU infection prevention data supports the CAPI concept. The CAPI model could account for some paradoxically high Acinetobacter and Pseudomonas infection incidences, most apparent among the concurrent control groups of TAP studies.

scholarly journals Incidences ofPseudomonas aeruginosa-Associated Ventilator-Associated Pneumonia within Studies of Respiratory Tract Applications of Polymyxin: Testing the Stoutenbeek Concurrency Postulates

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
James C. Hurley
Keyword(s):  
Respiratory Tract ◽  
Estimating Equation ◽  
Ventilator Associated Pneumonia ◽  
Control Groups ◽  
Content Type ◽  
Mechanically Ventilated ◽  
Concurrent Control ◽  
Component Group ◽  
Funnel Plots ◽  
The Mean

ABSTRACTRegimens containing topical polymyxin appear highly effective at preventing ventilator-associated pneumonia (VAP) overall and, more so, VAP caused by Gram-negative bacteria. However, Stoutenbeek's postulates that VAP incidences within studies of topical antibiotics depend on the context of whether the component (control and intervention) groups of each study were concurrent versus nonconcurrent remain untested. The literature was searched for concurrent control (CC) versus nonconcurrent control (NCC) designed studies of respiratory tract applications of topical polymyxin to mechanically ventilated (MV) patients that reported incidences ofPseudomonas-associated ventilator-associated pneumonia (PsVAP). Studies of various interventions other than topical polymyxin (nonpolymyxin studies) served to provide additional points of reference. The PsVAP incidences within the component groups of all studies were benchmarked against groups from observational studies. This was undertaken by meta-regression using generalized estimating equation methods. Dot plots, caterpillar plots, and funnel plots enable visual benchmarking. The PsVAP benchmark (and 95% confidence interval [CI]) derived from 102 observational groups is 4.6% (4.0 to 5.3%). In contrast, the mean PsVAP within NCC polymyxin intervention groups (1.6%; CI, 1.0 to 4.5%) is lower than that of all other component group categories. The mean PsVAP within CC polymyxin control groups (9.9%; CI, 7.6 to 12.8%) is higher than that of all other component group categories. The PsVAP incidences of control and intervention groups of studies of respiratory tract applications of polymyxin are dependent on whether the groups were within a concurrent versus nonconcurrent study. Stoutenbeek's concurrency postulates are validated.

scholarly journals Selective digestive decontamination, a seemingly effective regimen with individual benefit or a flawed concept with population harm?

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
James C. Hurley
Keyword(s):  
Antibiotic Prophylaxis ◽  
Natural Experiment ◽  
Evidence Base ◽  
Selective Digestive Decontamination ◽  
Topical Antibiotic ◽  
Parenteral Antibiotic ◽  
Concurrent Control ◽  
Effective Regimen ◽  
Highly Effective ◽  
Event Rates

AbstractSelective digestive decontamination (SDD) regimens, variously constituted with topical antibiotic prophylaxis (TAP) and protocolized parenteral antibiotic prophylaxis (PPAP), appear highly effective for preventing ICU-acquired infections but only within randomized concurrent control trials (RCCT’s). Confusingly, SDD is also a concept which, if true, implies population benefit. The SDD concept can finally be reified  in humans using the broad accumulated evidence base, including studies of TAP and PPAP that used non-concurrent controls (NCC), as a natural experiment. However, this test implicates overall population harm with higher event rates associated with SDD use within the ICU context.

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