Busting the Myth of “Static vs Cidal”: A Systemic Literature Review

Wald-Dickler, Noah; Holtom, Paul; Spellberg, Brad

doi:10.1093/cid/cix1127

Cited by 121 publications

(90 citation statements)

References 40 publications

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“…Reductions in colony count and size were statistically significant but within the timeframe of UVA exposure in our experiments (60 minutes or less), the bactericidal threshold of 1000-fold reduction (i.e. >99.9% reduction) in bacterial density [21] was not met for several microbes. Mechanisms underlying the antimicrobial effects of UV light are not fully known.…”

Section: Discussioncontrasting

confidence: 58%

Ultraviolet A light effectively reduces bacteria and viruses including coronavirus

et al. 2020

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Antimicrobial-resistant and novel pathogens continue to emerge, outpacing efforts to contain and treat them. Therefore, there is a crucial need for safe and effective therapies. Ultraviolet-A (UVA) phototherapy is FDA-approved for several dermatological diseases but not for internal applications. We investigated UVA effects on human cells in vitro, mouse colonic tissue in vivo, and UVA efficacy against bacteria, yeast, coxsackievirus group B and coronavirus-229E. Several pathogens and virally transfected human cells were exposed to a series of specific UVA exposure regimens. HeLa, alveolar and primary human tracheal epithelial cell viability was assessed after UVA exposure, and 8-Oxo-2'-deoxyguanosine was measured as an oxidative DNA damage marker. Furthermore, wild-type mice were exposed to intracolonic UVA as an in vivo model to assess safety of internal UVA exposure. Controlled UVA exposure yielded significant reductions in Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Clostridioides difficile, Streptococcus pyogenes, Staphylococcus epidermidis, Proteus mirabilis and Candida albicans. UVA-treated coxsackievirus-transfected HeLa cells exhibited significantly increased cell survival compared to controls. UVA-treated coronavirus-229E-transfected tracheal cells exhibited significant coronavirus spike protein reduction, increased mitochondrial antiviral-signaling protein and decreased coronavirus-229E-induced cell death. Specific controlled UVA exposure had no significant effect on growth or 8-Oxo-2'-deoxyguanosine levels in three types of human cells. Single or repeated in vivo intraluminal UVA exposure produced no discernible endoscopic, histologic or dysplastic changes in mice. These findings suggest that, under specific conditions, UVA reduces various pathogens including coronavirus-229E, and may provide a safe and effective treatment for infectious diseases of internal viscera. Clinical studies are warranted to further elucidate the safety and efficacy of UVA in humans.

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Section: Discussioncontrasting

confidence: 58%

Ultraviolet A light effectively reduces bacteria and viruses including coronavirus

et al. 2020

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“…Bacteriostatic agents may also kill bacteria, but a higher dosage is required (Wald‐Dickler et al . ). Over the course of this study, short‐term MSM treatment displayed a bacteriostatic phenotype; whereas, long‐term treatment displayed a bactericidal phenotype.…”

Section: Discussionmentioning

confidence: 97%

“…Bacteriostatic antimicrobials inhibit growth of bacteria by interfering with DNA replication, protein production or other metabolic functions without killing the cell (Wald-Dickler et al 2018). Cellular functions may resume if the drug is withdrawn before normal cellular functions are irreparably affected, particularly in vitro.…”

Section: Discussionmentioning

confidence: 99%

Methylsulfonylmethane exhibits bacteriostatic inhibition of Escherichia coli , and Salmonella enterica Kinshasa, in vitro

Poole

Benjamin²,

Genovese

et al. 2019

J Appl Microbiol

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Aims To evaluate antibacterial properties of methylsulfonylmethane (MSM) on Escherichia coli (MDRE21) and Salmonella enterica serovar Kinshasa (SK132). Methods and Results Bacterial proliferation analysis was measured spectrophotometrically during log phase growth with 0, 3, 5, 7, 10, 12 and 16% MSM. To assess the mechanism of inhibition, cultures were grown overnight with 0–16% MSM and enumerated on unmedicated brain–heart infusion agar (BHIA) or BHIA with 0–16% MSM. The long‐term viability studies were done to evaluate the impact of 10% MSM. Absorbance data indicated a dose‐dependent inhibition from 0 to 16% MSM. There was no growth of MDRE21 or SK132 on BHIA in 10–16% MSM. Both strains enumerated on unmedicated BHIA from overnight cultures with 10–16% MSM were able to partially recover. Conclusions Recovery after MSM removal may be indicative of a bacteriostatic mechanism of inhibition. The long‐term viability studies illustrated that neither MDRE21 nor SK132 could be rescued from 10% MSM after 5 or 6 days respectively. Significance and Impact of the Study Methylsulfonylmethane antibacterial activity may prove useful during pre or postharvest food safety as a disinfectant. The primary benefit being, its clinical safety to humans. Comparisons to other disinfectants would also need to be done to determine if MSM was superior to those already on the market and would be cost effective.

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“…We thus wondered at which level macrolides and tetracyclines exert a differential effect on gut microbes. Although traditionally both clinical use 34-37 and basic research 38,39 heavily rely on this distinction between bactericidal and bacteriostatic antibiotics, there are reports of drugs changing their killing capacity depending on the organism, drug concentration or medium tested 40,41 (and increased evidence from meta-analyses that the distinction may have little relevance to clinical practice 42,43 ). We therefore hypothesized that this bacteriostatic/bactericidal divide may be less rigid for gut commensals, which are more phylogenetically diverse than the few pathogens usually tested, and hence provide a level where the effect of these drug classes on gut microbes becomes differential.…”

Section: Main Textmentioning

confidence: 99%

Dissecting the collateral damage of antibiotics on gut microbes

Maier

Goemans

Pruteanu

et al. 2020

Preprint

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24Antibiotics are used for fighting pathogens, but also target our commensal bacteria as a side 25 effect, disturbing the gut microbiota composition and causing dysbiosis and disease 1-3 . 26Despite this well-known collateral damage, the activity spectrum of the different antibiotic 27 classes on gut bacteria remains poorly characterized. Having monitored the activities of 28 >1,000 marketed drugs on 38 representative species of the healthy human gut microbiome 4 , 29 we here characterize further the 144 antibiotics therein, representing all major classes. We 30 determined >800 Minimal Inhibitory Concentrations (MICs) and extended the antibiotic 31 profiling to 10 additional species to validate these results and link to available data on 32 antibiotic breakpoints for gut microbes. Antibiotic classes exhibited distinct inhibition spectra, 33including generation-dependent effects by quinolones and phylogeny-independence by β-34 lactams. Macrolides and tetracyclines, two prototypic classes of bacteriostatic protein 35 synthesis inhibitors, inhibited almost all commensals tested. We established that both kill 36 different subsets of prevalent commensal bacteria, and cause cell lysis in specific cases. 37This species-specific activity challenges the long-standing divide of antibiotics into 38 bactericidal and bacteriostatic, and provides a possible explanation for the strong impact of 39 macrolides on the gut microbiota composition in animals 5-8 and humans 9-11 . To mitigate the 40 collateral damage of macrolides and tetracyclines on gut commensals, we exploited the fact 41 that drug combinations have species-specific outcomes in bacteria 12 and sought marketed 42 drugs, which could antagonize the activity of these antibiotics in abundant gut commensal 43 species. By screening >1,000 drugs, we identified several such antidotes capable of 44 protecting gut species from these antibiotics without compromising their activity against 45 relevant pathogens. Altogether, this study broadens our understanding of antibiotic action on 46 gut commensals, uncovers a previously unappreciated and broad bactericidal effect of 47 prototypical bacteriostatic antibiotics on gut bacteria, and opens avenues for preventing the48 collateral damage caused by antibiotics on human gut commensals.49 3 MAIN TEXT 50 Medication is emerging as major contributor for changes in the composition of the human gut 51 microbiota 4,13-15 . Such severe and long-lasting changes are associated, and in some cases 52 causatively linked, to dysbiosis and a wide range of diseases 16 . Although several non-53 antibiotic drugs may also have a previously unappreciated impact on the gut microbiome 54 composition 4,16,17 , antibiotics, developed to have broad spectra and thereby target very 55 diverse pathogens, are long known to take a heavy toll on our gut flora, causing a variety of 56 gastrointestinal side-effects 18 , including Clostridioides (former Clostridium) difficile infections. 57Recently more attention has been given to this collateral damage of antibiot...

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Busting the Myth of “Static vs Cidal”: A Systemic Literature Review

Cited by 121 publications

References 40 publications

Ultraviolet A light effectively reduces bacteria and viruses including coronavirus

Ultraviolet A light effectively reduces bacteria and viruses including coronavirus

Methylsulfonylmethane exhibits bacteriostatic inhibition of Escherichia coli , and Salmonella enterica Kinshasa, in vitro

Dissecting the collateral damage of antibiotics on gut microbes

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