General Anesthesia Alters the Diversity and Composition of the Intestinal Microbiota in Mice. Serbanescu Mara A,Mathena Reilley P,Xu Jing,Santiago-Rodriguez Tasha,Hartsell Theresa L,Cano Raul J,Mintz Cyrus D Anesthesia and analgesia Dysbiosis of the intestinal microbiota has been shown to result in altered immune responses and increased susceptibility to infection; as such, the state of the intestinal microbiome may have profound implications in the perioperative setting. In this first-in-class study, we used 16s ribosomal RNA sequencing and analysis in a mouse model of general anesthesia to investigate the effects of volatile anesthetics on the diversity and composition of the intestinal microbiome. After 4-hour exposure to isoflurane, we observed a decrease in bacterial diversity. Taxonomic alterations included depletion of several commensal bacteria including Clostridiales. These data identify volatile anesthetics as potential contributors to microbial dysbiosis in the postoperative patient. 10.1213/ANE.0000000000003938
    The Differential Effects of Anesthetics on Bacterial Behaviors. Chamberlain Matthew,Koutsogiannaki Sophia,Schaefers Matthew,Babazada Hasan,Liu Renyu,Yuki Koichi PloS one Volatile anesthetics have been in clinical use for a long period of time and are considered to be promiscuous by presumably interacting with several ion channels in the central nervous system to produce anesthesia. Because ion channels and their existing evolutionary analogues, ion transporters, are very important in various organisms, it is possible that volatile anesthetics may affect some bacteria. In this study, we hypothesized that volatile anesthetics could affect bacterial behaviors. We evaluated the impact of anesthetics on bacterial growth, motility (swimming and gliding) and biofilm formation of four common bacterial pathogens in vitro. We found that commonly used volatile anesthetics isoflurane and sevoflurane affected bacterial motility and biofilm formation without any effect on growth of the common bacterial pathogens studied here. Using available Escherichia coli gene deletion mutants of ion transporters and in silico molecular docking, we suggested that these altered behaviors might be at least partly via the interaction of volatile anesthetics with ion transporters. 10.1371/journal.pone.0170089
    The antibacterial activity of tramadol against bacteria associated with infectious complications after local or regional anesthesia. Tamanai-Shacoori Zohreh,Shacoori Valliollah,Jolivet-Gougeon Anne,Vo Van Jean-Marie,Repère Martine,Donnio Pierre-Yves,Bonnaure-Mallet Martine Anesthesia and analgesia BACKGROUND:Tramadol is a synthetic analog of codeine with opioid and local anesthetic properties. It is used as a central-acting analgesic, and recently, in subcutaneous or intradermal injections, as a local anesthetic. We investigated in vitro the antibacterial activity of tramadol in the absence of any local anesthetics against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa pathogens that can cause infectious complications after local or regional anesthesia. METHODS:Bacterial cultures were grown for 18 h, diluted in sterile physiological saline, and incubated for 6 or 24 h at 37 degrees C with 6.25, 12.5, or 25 mg/mL tramadol. The mixtures were then plated onto blood agar and colony counts were recorded after 24 h incubation at 37 degrees C. RESULTS:Tramadol had bactericidal activity against E. coli and S. epidermidis compared with controls: at 25 mg/mL for 6 h or at 12.5 mg/mL for 24 h, tramadol decreased by approximately 7 log(10) (P < 0.001) the colony counts of E. coli (100% kill). Similar results were obtained with S. epidermidis, with approximately 6 log(10) reduction (100% kill) when tramadol was used at 25 mg/mL for 24 h (P < 0.001). The antibacterial effect of 25 mg/mL tramadol was lower against S. aureus and P. aeruginosa, reducing the growth of these strains by approximately 3log(10) after 24 h (P < 0.001). CONCLUSIONS:Tramadol has dose- and time-dependent bactericidal activity against E. coli and S. epidermidis, as well as antibacterial activity against S. aureus and P. aeruginosa. The antibacterial properties of tramadol may be useful for reducing the risk of bacterial infection after local or regional anesthesia. 10.1213/01.ane.0000267525.51017.b8
    Ropivacaine 0.1% with sufentanil 1 microg/mL inhibits in vitro growth of Pseudomonas aeruginosa and does not promote multiplication of Staphylococcus aureus. Kampe Sandra,Poetter Carsten,Buzello Shariah,Wenchel Hans-Martin,Paul Matthias,Kiencke Peter,Kasper Stefan-Mario Anesthesia and analgesia UNLABELLED:We investigated the effect of ropivacaine combined with sufentanil, a mixture frequently used for postoperative epidural analgesia, on the growth of Staphylococcus aureus and Pseudomonas aeruginosa at room temperature. Aliquots of suspension of S. aureus and P. aeruginosa in saline were transferred into test tubes containing either a mixture of ropivacaine 0.1% and sufentanil 1 microg/mL (R+S) or saline (SA), with the latter serving as control. At 0, 3, 6, 24, and 48 h after inoculation, 1 mL of each solution was spread over standard blood agar. The plates were incubated at 22 degrees C for 48 h, and the numbers of colony-forming units (cfu) were counted. The growth ratio for both bacterial strains was calculated as cfu time (t(n))/cfu baseline (t(0)). The primary efficacy variable was the area under the curve (AUC) in (cfu t(n)/cfu t(0)) x time, based on the growth ratios. The AUC for P. aeruginosa was significantly less in R+S than in SA (P = 0.028). Multiplication of P. aeruginosa (growth ratio >1) was observed for at least 6 h after inoculation in SA. Growth of P. aeruginosa was significantly less in R+S than in SA at 3 h (P = 0.043) and 24 h (P = 0.012) after inoculation. The AUC for S. aureus did not differ significantly between R+S and SA (P = 0.74). Neither R+S nor SA promoted multiplication of S. aureus. Forty-eight hours after inoculation, growth of S. aureus was significantly less in R+S than in SA (P < 0.0001). We conclude that R+S inhibited growth of P. aeruginosa and did not promote multiplication of S. aureus when compared with SA. IMPLICATIONS:This laboratory study demonstrated that compared with saline, ropivacaine 0.1% with 1 microg/mL of sufentanil inhibited growth of Pseudomonas aeruginosa and did not promote multiplication of Staphylococcus aureus at room temperature. With respect to bacterial infection with these two strains, the mixture seems to be safe for continuous epidural administration if prepared under aseptic conditions and after alcohol hand rub. 10.1213/01.ane.0000067404.84486.7a
    Pseudomonas aeruginosa overrides the virulence inducing effect of opioids when it senses an abundance of phosphate. Zaborin Alexander,Gerdes Svetlana,Holbrook Christopher,Liu Donald C,Zaborina Olga Y,Alverdy John C PloS one The gut during critical illness represents a complex ecology dominated by the presence of healthcare associated pathogens, nutrient scarce conditions, and compensatory host stress signals. We have previously identified key environmental cues, opioids and phosphate depletion that independently activate the virulence of Pseudomonas aeruginosa. Opioids induce quinolone signal production (PQS), whereas phosphate depletion leads to a triangulated response between MvfR-PQS, pyoverdin, and phosphosensory/phosphoregulatory systems (PstS-PhoB). Yet how P. aeruginosa manages its response to opioids during nutrient scarce conditions when growth is limited and a quorum is unlikely to be achieved is important in the context of pathogenesis in gut during stress. To mimic this environment, we created nutrient poor conditions and exposed P. aeruginosa PAO1 to the specific k-opioid receptor agonist U-50,488. Bacterial cells exposed to the k-opioid expressed a striking increase in virulence- and multi-drug resistance-related genes that correlated to a lethal phenotype in C. elegans killing assays. Under these conditions, HHQ, a precursor of PQS, rather than PQS itself, became the main inducer for pqsABCDE operon expression. P. aeruginosa virulence expression in response to k-opioids required PqsE since ΔPqsE was attenuated in its ability to activate virulence- and efflux pumps-related genes. Extracellular inorganic phosphate completely changed the transcriptional response of PAO1 to the k- opioid preventing pqsABCDE expression, the activation of multiple virulence- and efflux pumps-related genes, and the ability of P. aeruginosa to kill C. elegans. These results indicate that when P. aeruginosa senses resource abundance in the form of phosphate, it overrides its response to compensatory host signals such as opioids to express a virulent and lethal phenotype. These studies confirm a central role for phosphate in P. aeruginosa virulence that might be exploited to design novel anti- virulence strategies. 10.1371/journal.pone.0034883
    Chronic opioid use is associated with altered gut microbiota and predicts readmissions in patients with cirrhosis. Acharya C,Betrapally N S,Gillevet P M,Sterling R K,Akbarali H,White M B,Ganapathy D,Fagan A,Sikaroodi M,Bajaj J S Alimentary pharmacology & therapeutics BACKGROUND:Opioid use is epidemic in cirrhosis, which could precipitate hepatic encephalopathy (HE) potentially through gut dysbiosis and inflammation. AIM:To define the effect of opioids on readmissions and on gut microbiota composition and functionality. METHODS:Cohort 1 had 200 cirrhotic in-patients (with/without opioid use) followed prospectively through the index hospitalisation and 6 months post discharge. Readmissions (HE-related/unrelated) were compared between patients discharged on opioids compared to the rest, including using a multi-variable analysis. Cohort 2 consisted of 72 cirrhotics on chronic opioids who were age/model for end-stage liver disease (MELD) and prior HE-balanced with 72 cirrhotics not on opioids. Stool microbiota composition (multi-tagged sequencing), predicted functionality (PiCRUST), endotoxemia and systemic inflammation (IL-6, IL-17) were compared. RESULTS:Cohort 1: Chronic opioid use was statistically similar between those admitted with/without HE, and was judged to be an HE precipitant in <5% of cases during the index hospitalisation. Of the 144 patients alive at 6 months, 82 were readmitted. The opioid users had a significantly higher all cause (69% vs. 48%, P = 0.008), but not HE-related readmissions (30% vs. 41%, P = 0.30). On regression, opioid therapy and female gender were predictive of readmission independent of MELD score and previous HE. Cohort 2: Significant dysbiosis was noted in the opioid cohort, especially in HE+opioid patients with lower autochthonous taxa and Bacteroidaceae relative abundance. PiCRUST showed highest aromatic amino acid and endotoxin production in opioid users. Opioid users also had higher endotoxemia and IL-6 but not IL-17. CONCLUSION:Chronic opioid use in cirrhosis is associated with increased endotoxemia, dysbiosis and all-cause readmissions. 10.1111/apt.13858
    Opioid analgesics stop the development of clostridial gas gangrene. Chakravorty Anjana,Awad Milena M,Hiscox Thomas J,Cheung Jackie K,Choo Jocelyn M,Lyras Dena,Rood Julian I The Journal of infectious diseases Gas gangrene is a potentially fatal disease that is primarily caused by the ubiquitous, anaerobic bacteria Clostridium perfringens and Clostridium septicum. Treatment is limited to antibiotic therapy, debridement of the infected tissue, and, in severe cases, amputation. The need for new treatment approaches is compelling. Opioid-based analgesics such as buprenorphine and morphine also have immunomodulatory properties, usually leading to faster disease progression. However, here we show that mice pretreated with buprenorphine and morphine do not die from clostridial myonecrosis. Treatment with buprenorphine after the onset of infection also arrested disease development. Protection against myonecrotic disease was specific to C. perfringens-mediated myonecrosis; buprenorphine did not protect against disease caused by C. septicum infection even though infections due to both species are very similar. These data provide the first evidence of a protective role for opioids during infection and suggest that new therapeutic strategies may be possible for the treatment of C. perfringens-mediated myonecrosis. 10.1093/infdis/jiu101
    Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection. Mora Andrea L,Salazar Miguel,Pablo-Caeiro Juan,Frost Craig P,Yadav Yashoo,DuPont Herbert L,Garey Kevin W The American journal of the medical sciences INTRODUCTION:Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. METHODS:Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. RESULTS:During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. CONCLUSIONS:Moderate to high use of opioid analgesics were associated with an increased risk of CDI. 10.1097/MAJ.0b013e31822f42eb
    Growth of Staphylococcus aureus in four intravenous anesthetics. Sosis M B,Braverman B Anesthesia and analgesia Patient infections related to the use of propofol have been reported. To investigate the growth of Staphylococcus aureus in propofol, thiopental, methohexital, etomidate, and 0.9% saline containing no bacteriostatic drug, these preparations were inoculated and samples were plated onto blood agar at 0, 3, 6, 21, 24, and 27 h. The number of colony-forming units (CFU) on the plates was then determined after 24 h of incubation. Samples from the inoculated etomidate solution showed zero CFU at 3 h and thereafter, whereas 21 h were required by the methohexital and thiopental solutions to reduce the number of CFU to zero. For normal saline, no significant change in CFU was seen before the first 6 h, then the number of CFU gradually declined, although some S. aureus CFU were still present at 27 h. Inoculation of the propofol emulsion resulted in a substantial growth of S. aureus between 6 and 21 h after inoculation. We conclude that, of the preparations tested, only propofol was an excellent medium for the rapid growth of S. aureus. Meticulous sterile technique, therefore, is advised when handling it.
    The effects of thiopentone, etomidate, ketamine and midazolam on several bactericidal functions of polymorphonuclear leucocytes in vitro. Krumholz W,Demel C,Jung S,Meuthen G,Knecht J,Hempelmann G European journal of anaesthesiology Polymorphonuclear leucocytes (PMNL) are an essential component of the defence system against invading bacteria. There is evidence that some anaesthetics are able to suppress PMNL functions, promoting, perhaps, perioperative infection. We studied the effects of thiopentone, etomidate, ketamine, and midazolam on the generation of bactericidal agents (superoxide anion, hydrogen peroxide, and myeloperoxidase) by PMNL in vitro. Thiopentone inhibited superoxide anion (P < or = 0.01) as well as hydrogen peroxide production (P < or = 0.001). However, there was no statistically significant effect on myeloperoxidase release. Neither etomidate nor ketamine influenced the PMNL functions tested to any extent. Midazolam suppressed superoxide anion generation (P < or = 0.01) but only if a concentration far beyond clinical relevance was used.
    Comparison of antimicrobial effects of dexmedetomidine and etomidate-lipuro with those of propofol and midazolam. Keleş G T,Kurutepe S,Tok D,Gazi H,Dinç G European journal of anaesthesiology BACKGROUND AND OBJECTIVES:The aim of our study was to investigate the antimicrobial effects of dexmedetomidine and etomidate-lipuro, and to compare these effects with those of midazolam and propofol on Staphylococcus aureus, Escherichia coli, Pseudomonas aeroginosa, Acinetobacter baumannii and extended-spectrum beta-lactamase Escherichia coli ( E. coli ESBL). METHODS:All hypnotic dilutions were exposed to micro-organisms for 0, 30, 60, 120 and 240 min at room temperature in vitro. The inoculums taken from diluted suspensions were re-inoculated on blood agar and incubated for 18-24 h at 35 degrees C after which a count of the colonies was compared. RESULTS:Midazolam reduced the viable cells of S. aureus at 30, 60, 120 and 240 min, and also completely inhibited the growth of E. coli, P. aeroginosa, A. baumannii and E. coli ESBL. Dexmedetomidine, etomidate-lipuro and propofol, however, did not inhibit any of the micro-organisms tested. CONCLUSION:In vitro, midazolam had an antimicrobial effect on E. coli, P. aeroginosa, A. baumannii and E. coli ESBL. Like propofol and dexmedetomidine, etomidate-lipuro had no antimicrobial effect on any of the micro-organisms tested. 10.1017/S0265021506000949
    The microbiological and sustainability effects of washing anaesthesia breathing circuits less frequently. McGain F,Algie C M,O'Toole J,Lim T F,Mohebbi M,Story D A,Leder K Anaesthesia In the presence of single-use airway filters, we quantified anaesthetic circuit aerobic microbial contamination rates when changed every 24 h, 48 h and 7 days. Microbiological samples were taken from the interior of 305 anaesthetic breathing circuits over a 15-month period (3197 operations). There was no significant difference in the proportion of contaminated circuits when changed every 24 h (57/105 (54%, 95% CI 45-64%)) compared with 48 h (43/100 (43%, 95% CI 33-53%, p = 0.12)) and up to 7 days (46/100 (46%, 95% CI 36-56%, p = 0.26)). Median bacterial counts were not increased at 48 h or 7 days provided circuits were routinely emptied of condensate. Annual savings for one hospital (six operating theatres) were $AU 5219 (£3079, €3654, $US 4846) and a 57% decrease in anaesthesia circuit steriliser loads associated with a yearly saving of 2760 kWh of electricity and 48 000 l of water. Our findings suggest that extended circuit use from 24 h up to 7 days does not significantly increase bacterial contamination, and is associated with labour, energy, water and financial savings. 10.1111/anae.12563
    Sensitivity of respiratory bacteria to lignocaine. Chandan Snehal S,Faoagali Joan,Wainwright Claire E Pathology AIM:Lignocaine, a topical anaesthetic agent, is generally used in variable concentrations usually between 2% and 4% on the vocal cords prior to flexible bronchoscopy and bronchoalveolar lavage (BAL) procedures. The aim of this study was to investigate whether 2% or 1% lignocaine significantly inhibits the growth of organisms commonly found in the respiratory tract, in particular Streptococcus pneumoniae. METHOD:In order to determine the antibiotic effect of lignocaine on lower respiratory tract flora, five different organisms were examined in vitro using well diffusion, disc diffusion and microbroth dilution against 1% and 2% concentrations of lignocaine. RESULTS:Antimicrobial activity could not be detected using the well diffusion and the disc diffusion methods, as lignocaine failed to diffuse through the media. The microbroth dilution method showed reproducible bactericidal effect of these respiratory isolates against Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae at 2% concentration. Lignocaine 2% showed no growth inhibition against Pseudomonas aeruginosa and Candida albicans. Lignocaine 1% also partially inhibited S. pneumoniae. CONCLUSION:As lignocaine shows significant inhibition of respiratory pathogens such as Streptococcus pneumoniae even at a concentration of 1%, the lowest concentration possible should be used for flexible bronchoscopy and BAL to maximise the chance of recovery of these organisms. 10.1080/00313020500168752
    In vitro antibacterial effects of topical local anesthetics. Sedef Gocmen J,Buyukkocak Unase,Caglayan Osman,Aksoy Altan The Journal of dermatological treatment BACKGROUND:The antibacterial activities of local anesthetics are recognized. OBJECTIVE:To investigate in vitro the activity of topical local anesthetic ointments at clinical doses. METHODS:The activity of two different local anesthetic ointments including lidocaine 5% and lidocaine/prilocaine 2.5% was tested against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes and Enterococcus faecalis by the disc-diffusion method. Sterile discs containing topical local anesthetic drugs were prepared taking into account the doses of ointments used in clinical practice. The validity of the methodology was confirmed using topical antibacterial mupirocin. The inhibition zones of the discs were measured. RESULTS:Mupirocin inhibited all the bacteria. Both local anesthetic ointments were found to be most effective on E. coli, whereas they had no effects on P. aeruginosa. Lidocaine 5% revealed antibacterial activity against S. aureus, S. epidermidis, E. coli, S. pyogenes and E. faecalis, but lidocaine/prilocaine 2.5% showed no activity on E. faecalis and inhibited S. pyogenes only at double doses. It was also observed that the antibacterial activity was in a dose-dependent manner. CONCLUSION:In the light of these findings, it might be concluded that topical local anesthetic ointments in routine settings may have a preventive role against some bacteria. 10.1080/09546630802050498
    Local anesthetics as antimicrobial agents: a review. Johnson Svena M,Saint John Barbara E,Dine Alan P Surgical infections BACKGROUND:Since the introduction of cocaine in 1884, local anesthetics have been used as a mainstay of pain management. However, numerous studies over the past several decades have elucidated the supplemental role of local anesthetics as antimicrobial agents. In addition to their anesthetic properties, medications such as bupivacaine and lidocaine have been shown to exhibit bacteriostatic, bactericidal, fungistatic, and fungicidal properties against a wide spectrum of microorganisms. METHODS:A comprehensive literature search was conducted using MEDLINE 1950-present for in vitro and in vivo studies pertaining to the antimicrobial activity of various local anesthetics on a broad range of bacterial and fungal pathogens. Studies testing the effect on microbial growth inhibition of local anesthetics alone and in combination with other agents, such as preservatives and other medications, as well as the effect of conditions such as concentration and temperature, were included for review. Outcome measures included colony counts, area-under-the-curve and time-kill curve calculations, minimum inhibitory concentrations, and post-antibiotic effect. RESULTS:Evidence suggests that local anesthetics as a class possess inherent antimicrobial properties against a wide spectrum of human pathogens. Multiple local anesthetics at concentrations typically used in the clinical setting (e.g., bupivacaine 0.125%-0.75%; lidocaine 1%-3%) inhibit the growth of numerous bacteria and fungi under various conditions. Different local anesthetics showed various degrees of antimicrobial capacity; bupivacaine and lidocaine, for example, inhibit growth to a significantly greater extent than does ropivacaine. Greater concentrations, longer exposure, and higher temperature each correlate with a proportional increase in microbial growth inhibition. Addition of other agents to the anesthetic solutions, such as preservatives, opioids, or intravenous anesthetics such as propofol, modify the antimicrobial activity via either synergistic or antagonistic action. Limited studies attribute the mechanism of action of antimicrobial activity of local anesthetics to a disruption of microbial cell membrane permeability, leading to leakage of cellular components and subsequent cell lysis. CONCLUSIONS:Local anesthetics not only serve as agents for pain control, but possess antimicrobial activity as well. In such a capacity, local anesthetics can be considered as an adjunct to traditional antimicrobial use in the clinical or laboratory setting. Additionally, caution should be exercised when administering local anesthetics prior to diagnostic procedures in which culture specimens are to be obtained, as the antimicrobial activity of the local anesthetic could lead to false-negative results or suboptimal culture yields. 10.1089/sur.2007.036
    Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties. Getachew Bruk,Aubee Joseph I,Schottenfeld Richard S,Csoka Antonei B,Thompson Karl M,Tizabi Yousef BMC microbiology BACKGROUND:Appreciable evidence suggest that dysbiosis in microbiota, reflected in gut microbial imbalance plays a key role in the pathogenesis of neuropsychiatric disorders including depression and inflammatory diseases. Recently, the antidepressant properties of ketamine have gained prominence due to its fast and long lasting effects. Additional uses for ketamine in inflammatory disorders such as irritable bowel syndrome have been suggested. However, ketamine's exact mechanism of action and potential effects on microbiome is not known. Here, we examined the effects of low dose ketamine, known to induce antidepressant effects, on stool microbiome profile in adult male Wistar rats. Animals (5/group) were injected intraperitoneally with ketamine (2.5 mg/kg) or saline, daily for 7 days and sacrificed on day 8 when intestinal stools were collected and stored at - 80 °C. DNA was extracted from the samples and the 16 S rRNA gene-based microbiota analysis was performed using 16S Metagenomics application. RESULTS:At genus-level, ketamine strikingly amplified Lactobacillus, Turicibacter and Sarcina by 3.3, 26 and 42 fold, respectively. Conversely, opportunistic pathogens Mucispirillum and Ruminococcus were reduced by approximately 2.6 and 26 fold, respectively, in ketamine group. Low levels of Lactobacillus and Turicibacter are associated with various disorders including depression and administration of certain species of Lactobacillus ameliorates depressive-like behavior in animal models. Hence, some of the antidepressant effects of ketamine might be mediated through its interaction with these gut bacteria. Additionally, high level of Ruminococcus is positively associated with the severity of irritable bowel syndrome (IBS), and some species of Mucispirillum have been associated with intestinal inflammation. Indirect evidence of anti-inflammatory role of Sarcina has been documented. Hence, some of the anti-inflammatory effects of ketamine and its usefulness in specific inflammatory diseases including IBS may be mediated through its interaction with these latter bacteria. CONCLUSION:Our data suggest that at least some of the antidepressant and anti-inflammatory effects of daily ketamine treatment for 7 days may be mediated via its interaction with specific gut bacteria. These findings further validate the usefulness of microbiome as a target for therapeutic intervention and call for more detailed investigation of microbiome interaction with central mediators of mood and/or inflammatory disorders. 10.1186/s12866-018-1373-7
    Local anesthetics impair human granulocyte phagocytosis activity, oxidative burst, and CD11b expression in response to Staphylococcus aureus. Kiefer Ralph-Thomas,Ploppa Annette,Krueger Wolfgang A,Plank Michael,Nohé Boris,Haeberle Helene A,Unertl Klaus,Dieterich Hans-Jürgen Anesthesiology BACKGROUND:With invasion of bacteria, the host defense system is activated by a complex cascade of various mechanisms. Local anesthetics previously were shown to interact with diverse components of the immune response, such as leukocyte adherence on endothelial monolayers, oxidative burst, or crosstalk within lymphocyte subset populations. However, effects of newer local anesthetics like bupivacaine and ropivacaine on antibacterial host defense-primarily phagocytosis activity, oxidative burst, or CD11b expression-still remain unclear. METHODS:Whole blood samples were preincubated with local anesthetics (lidocaine, 9.2, 92.2, and 1,846 microm bupivacaine, 6.1, 61, and 770 microm; ropivacaine, 6.4, 64, and 801 microm). For the oxidative burst and CD11b assay, dihydroethidium was added to the probes. After viable Staphylococcus aureus was added in a 5 to 1 ratio following leukocyte count, phagocytosis was stopped at different times, and staining with monoclonal antibodies was performed for subsequent flow cytometric analysis of phagocytosis activity, oxidative burst, and CD11b expression. RESULTS:Granulocyte phagocytosis activity, CD11b expression, and generation of reactive oxygen species were significantly reduced by lidocaine (P < 0.0002) and bupivacaine (P < 0.005) in the highest concentration (1,846 microm and 770 microm, respectively). The capability of granulocytes to ingest bacteria was significantly depressed only by lidocaine (P < 0.003). Ropivacaine had no significant effect on any parameter investigated. CONCLUSIONS:Local anesthetic dose and structure dependently inhibit inflammatory and immunologic parameters of granulocyte functions. Ropivacaine shows low interference with granulocyte immunologic and inflammatory functions. 10.1097/00000542-200304000-00009
    Antimicrobial activity of ropivacaine and other local anaesthetics. Aydin O N,Eyigor M,Aydin N European journal of anaesthesiology BACKGROUND AND OBJECTIVE:It is claimed that local anaesthetics have antimicrobial properties. Our aim was to investigate the antimicrobial effects of different concentrations of ropivacaine, bupivacaine, lidocaine and prilocaine on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. METHODS:All local anaesthetic dilutions were exposed to microorganisms for 0, 30, 60, 120, 240 min at room temperature. The inoculums taken from diluted suspensions were reinoculated on blood agar and incubated for 18-24 h at 35 degrees C and then the colonies were counted. RESULTS:Ropivacaine did not inhibit any of the microorganisms tested. Bupivacaine reduced the viable cells of P. aeruginosa at 0.5% and 0.25% solutions. Lidocaine 5% and 2% and prilocaine 2.0% dilutions reduced the viable cells of all microorganisms tested. Prilocaine 1.0% reduced the viable cells of E. coli, S. aureus and P. aeruginosa. Lidocaine 1% reduced only the viable cells of P. aeruginosa and prilocaine 0.5% reduced only E. coli. CONCLUSION:Ropivacaine had no antimicrobial effect on microorganisms tested. Bupivacaine showed poor antimicrobial effectiveness. Lidocaine and prilocaine had more powerful antimicrobial effects than the other two local anaesthetics.
    Local anesthetics time-dependently inhibit staphylococcus aureus phagocytosis, oxidative burst and CD11b expression by human neutrophils. Ploppa Annette,Kiefer Ralph-Thomas,Krueger Wolfgang A,Unertl Klaus E,Durieux Marcel E Regional anesthesia and pain medicine BACKGROUND AND OBJECTIVES:Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, which might help to prevent inflammatory injury to the organism. However, if host defense mechanisms are affected similarly, the ability to eliminate bacteria might be reduced. We hypothesized that local anesthetics have time-dependent effects on phagocytosis of S. aureus, oxidative burst, and CD11b expression by human neutrophils. To test this hypothesis, we reanalyzed data from a previous study. METHODS:Blood samples from 11 healthy volunteers were incubated with lidocaine (1,846 mumol/L), bupivacaine (770 mumol/L) or ropivacaine (801 mumol/L) for 30 minutes. Thereafter, bacteria were added, either fluorescently labeled for determination of phagocytosis, or unstained for determination of oxidative burst and CD11b expression. After an additional incubation for 0, 10, 30, or 60 minutes, phagocytosis was stopped and neutrophils were stained with monoclonal antibodies for flow cytometric analysis. Data were analyzed by analysis of variance for repeated measurements. RESULTS:Lidocaine and bupivacaine inhibited neutrophil functions in a time-dependent manner (P < .05). Prolonged local anesthetic exposure reduced the fraction of ingesting neutrophils by 20% +/- 12% (mean +/- SD) and 7% +/- 7%, bacterial uptake by 19% +/- 16% and 14% +/- 12%, oxidative burst by 29% +/- 23% and 28% +/- 25%, and CD11b expression by 66% +/- 24% and 25% +/- 21% for lidocaine and bupivacaine, respectively. Ropivacaine exerted a time-dependent effect on CD11b expression only (24% +/- 34%; P < .05). CONCLUSIONS:Our results indicate that in a whole blood model, time-dependent effects of local anesthetics affect key neutrophil functions necessary for bacterial elimination. However, these effects only occur at concentrations that are unlikely to be routinely attained in the clinical setting, and concern about interfering with the host defense is likely unwarranted. 10.1016/j.rapm.2007.05.012
    Volatile Anesthetic Attenuates Phagocyte Function and Worsens Bacterial Loads in Wounds. Koutsogiannaki Sophia,Bernier Rachel,Tazawa Kazumasa,Yuki Koichi The Journal of surgical research BACKGROUND:Previously we have shown that volatile anesthetic isoflurane attenuated neutrophil recruitment and phagocytosis in mouse sepsis and skin inflammation models. The objectives of this study were to test ex vivo function of neutrophils in patients who underwent cardiac catheterization under volatile anesthesia versus intravenous anesthesia (IA), and also to assess the effect of anesthesia on surgical site infections (SSIs) using mouse model to understand the clinical relevance of anesthesia-induced immunomodulation. METHODS:Whole blood from patients who underwent cardiac catheterization procedures either by volatile anesthesia or IA was collected and subjected to phagocytosis assay and a lipopolysaccharide-induced tumor necrosis factor-α assay. Mouse SSI with Staphylococcus aureus USA300 was created, and the effect of isoflurane and propofol exposure (short or long exposure) on bacterial loads was tested. RESULTS:Neutrophil phagocytosis was significantly attenuated after the induction of volatile anesthesia in patients, but not by IA. Monocyte phagocytosis was not affected by the anesthesia regimen. Bacterial loads following SSIs were significantly higher in mice receiving long, but not short, isoflurane exposure. Propofol exposure did not affect bacterial loads. DISCUSSION:Neutrophil phagocytosis can be affected by the type of anesthesia, and preclinical model of SSIs showed potential clinical relevance. The effects of anesthesia regimen on SSIs in patients needs to be studied extensively in the future. 10.1016/j.jss.2018.07.075
    Do local anesthetics have antibacterial effect on Staphylococcus aureus under in vivo conditions? An experimental study. Kose A Aydan,Karabaggli Yakup,Kiremitci Abdurrahman,Kocman Emre,Cetin Cengiz Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] OBJECTIVE:The antimicrobial properties against Staphylococcus aureus of some common local anesthetic preparations such as prilocaine, bupivacaine, articaine, and combinations were evaluated in a live rat surgical wound model. METHODS:This study was conducted at the animal research laboratory of Eskisehir Osmangazi University in 2003. Clean surgical wounds were created after local anesthetic application and inoculated with S. aureus (10(2) colony forming units/mL). Four days later, tissue cultures were harvested from control animals and animals given local anesthetic to determine the quantity of bacteria. RESULTS:The tissue cultures demonstrated that none of the local anesthetics used in the study showed any inhibitory or bactericidal activity on S. aureus. There was no statistical difference in bacterial count between the local anesthetic-treated and control group wounds. CONCLUSION:The results of the present study did not show any antimicrobial activity of above-mentioned local anesthetics in surgically created wounds of rats. 10.1111/j.1524-4725.2010.01559.x
    Interaction of local anaesthetics with other antifungal agents against pathogenic Aspergillus. Rodrigues Acacio Gonçalves,Araujo Ricardo,Pina-Vaz Cidalia International journal of antimicrobial agents Aspergillus spp. are responsible for an increasing number of fungal infections in immunocompromised and transplant patients. Local anaesthetics (LAs) are growth inhibitors of bacteria and yeasts. Subinhibitory concentrations of the LAs lidocaine and bupivacaine blocked the germination of Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger whilst also showing a positive interaction in vitro with the antifungal activity of amphotericin B, itraconazole and caspofungin and a negative interaction with voriconazole. At higher concentrations, both LAs present fungicidal activity against resting conidia owing to cell membrane lesions. Verapamil, nifedipine and lanthanum produced a similar inhibitory effect on conidia germination. Calcium chloride reverted the inhibitory effect of verapamil and LAs. This study highlights that drug interactions may affect the clinical efficacy of antifungals, either promoting or limiting their action. 10.1016/j.ijantimicag.2005.11.011
    The antimicrobial activity of bupivacaine, lidocaine and mepivacaine against equine pathogens: An investigation of 40 bacterial isolates. Adler D M T,Damborg P,Verwilghen D R Veterinary journal (London, England : 1997) Lameness is the most commonly reported health problem in horses, and lameness investigations which include local anaesthetic injections are routinely performed by equine practitioners. Through this process, bacteria can enter the tissues perforated by the needle and may cause local infections at the injection site. The objective of this in vitro study was to investigate if local anaesthetics at concentrations available in commercially available solutions could inhibit growth and/or kill bacteria that could be inoculated into the synovial space or soft tissues during injection. This study evaluated the antimicrobial activity of the local anaesthetics bupivacaine, lidocaine and mepivacaine against 40 equine clinical bacterial isolates of the Actinobacillus, Corynebacterium, Enterobacter, Escherichia, Pseudomonas, Rhodococcus, Staphylococcus and Streptococcus genera. Minimum inhibitory and minimum bactericidal concentrations (MICs and MBCs) were determined by the broth microdilution method. Clinically applied concentrations of bupivacaine, lidocaine, and mepivacaine inhibited visual growth of 93%, 93%, and 80% of isolates tested, respectively. For the majority (80%) of the inhibited isolates, the concentrations were also bactericidal. The tested local anaesthetics possessed antimicrobial activity against equine pathogens at concentrations that are routinely applied in clinical cases. However, this antimicrobial activity should not discourage antiseptic preparation prior to local anaesthetic injections. 10.1016/j.tvjl.2017.05.001
    Microbial stability of syringes of anesthetic drugs prepared in the operating room. Segal Scott,Gunawan Antonius,McLaughlin Douglas H,Palavecino Elizabeth Journal of clinical anesthesia STUDY OBJECTIVE:To determine whether microbial contamination of anesthesia syringes prepared in the operating room (OR) become contaminated in a time-dependent fashion. DESIGN:Observational. SETTING:Operating suite in a major university hospital. PATIENTS:None (in vitro study). 400 syringes were studied for microbial contamination. INTERVENTIONS:Syringes prepared in the OR by anesthesia personnel were sampled at 1, 2, 3, or 4 h in a sterile fashion and sent to the microbiology laboratory for quantitative culture of any bacteria. MEASUREMENTS:Colony forming units (CFU) per mL of drug were calculated and any identified positive cultures were identified by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry. Logistic regression was used to test the effect of time since preparation on prevalence of positive culture, as was the effect of number of accesses of the syringe and identity of the drug. MAIN RESULTS:Overall, 9/400 (2.25%) syringes were positive for bacteria. The median (interquartile range [IQR]) concentration of bacteria among positive cultures was 100 (100,100) CFU. All cultured species were generally nonpathogenic common contaminants. There was no effect of time since preparation, number of accesses of the syringe at the time of sampling, or drug identity (propofol vs. other). CONCLUSIONS:Contamination of anesthesia syringes is uncommon and occurs at a low overall concentration of bacteria. Contamination does not appear to be time related, and thus calls into question the reasonableness of USP Chapter 797's one-hour requirement. 10.1016/j.jclinane.2018.12.029
    Analysis of the antimicrobial activity of local anaesthetics used for dental analgesia. Pelz Klaus,Wiedmann-Al-Ahmad Margit,Bogdan Christian,Otten Jörg-Elard Journal of medical microbiology Seven local anaesthetics and their active anaesthetic components [Ultracaine D-S (articaine hydrochloride), Carbostesin (bupivacaine hydrochloride), Scandicaine (mepivacaine hydrochloride), Xylonest (prilocaine hydrochloride), Xylocaine (lidocaine hydrochloride), Hostacaine (butanilicaine phosphate) and Novocaine (procaine hydrochloride)] were tested for their antimicrobial activity against 311 bacterial strains from 52 different species and 14 Candida albicans strains. The tested pathogens were members of the oral flora, and partly members of the skin and intestinal flora. Additionally, the antimicrobial activity of methyl-4-hydroxybenzoate, sodium disulfite, adrenaline hydrogen tartrate and adrenaline (the preservative and vasoconstrictive components of the anaesthetics) was tested. For determination of MIC and minimal bactericidal concentration (MBC), the agar dilution method using Wilkins-Chalgren agar was applied. The trade preparation Ultracaine D-S showed the most prominent antimicrobial activity with regard to both MIC and MBC. Ultracaine D-S and its active substance, articaine hydrochloride, showed similar MIC values, suggesting that the antimicrobial activity is mainly caused by the anaesthetic component. Novocaine showed the lowest antimicrobial activity and did not inhibit 35 of the species tested. The MIC values of all local anaesthetics were between 0.25 and 16 mg ml(-1). The routinely applied concentration of Ultracaine D-S was roughly four times higher, and of Hostacaine was two times higher, than the MBC values for the tested bacteria, whereas for the other anaesthetics, the MBC values were not reached or exceeded with the concentrations used. The MIC range of the preservatives was 0.5-1.0 mg ml(-1) for methyl-4-hydroxybenzoate and 0.2-0.5 mg ml(-1) for sodium disulfite. The articaine MIC values were two to three serial dilution steps lower, and the butanilicaine MIC values one to two serial dilution steps lower, than the MIC of the preservatives. The mepivacaine mean MIC values were slightly lower for Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis and Staphylococcus aureus, but higher for Streptococcus intermedius, compared with the preservative methyl-4-hydroxybenzoate. The same result was found with Streptococcus intermedius and lidocaine. Screening of 20 MIC values of 4 pure anaesthetic substances and the corresponding preservative found 2/20 instances where the MICs of the preservatives against 5 representative species (67 strains) were lower, indicating that the antimicrobial effect was mainly due to the preservative, but 18/20 results where the pure anaesthetic component showed greater antimicrobial effects compared with the preservative. The in vitro results for Carbostesin, Scandicaine and especially for Novocaine indicate that a local disinfection should be done prior to injection of the anaesthetics. Due to the results obtained with nosocomial strains (Escherichia coli, S. aureus and Pseudomonas), disinfection of the mucous membranes should be performed routinely in immunocompromised patients, regardless of the anaesthetic used. 10.1099/jmm.0.47339-0
    A review and new insights to antimicrobial action of local anesthetics. Razavi Bibi Marjan,Fazly Bazzaz Bibi Sedigheh European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology Local anesthetics (LAs) are medications which can provide analgesia in distinct body regions through the blockade of voltage-gated sodium channels. Besides pain management, the supplemental role of LAs as antimicrobial agents has been documented in several studies. Different databases including PubMed, Scopus, and Web of Science with the name of different local anesthetics and related names for antimicrobial keywords were searched without time limitation. This review summarized different in vitro and in vivo studies regarding antimicrobial effects of different LAs with focuses on antimicrobial applications of most studied LAs, interaction with different agents which combined with LAs, and mechanisms of action and structural dependence of LAs antibacterial effects. Among different LAs, lidocaine is the most studied preparation. Reduction of the incidence of endophthalmitis after intravitreal injection, prophylaxis for surgical wound infections, prevention of the incidence of catheter-associated infections, oral biofilm reduction on the buccal mucosa, and prevention against bacteria that produced nosocomial infection are some examples of lidocaine antimicrobial application. Studies showed that different factors including structure, concentration, duration of exposure, type of microorganism tested, and temperature affect the degree of LA antimicrobial activity. In addition, various agents such as antibiotics, preservatives, opioids, epinephrine, and propofol can combine with LAs and affect their antimicrobial properties through synergistic or antagonistic action. Due to antibacterial activities, LAs could be applied in a clinic for prophylaxis of surgical site infection. In the application of LAs prior to diagnostic procedures caution should be needed; otherwise, when culturing the specimen, they could lead to false negative results. 10.1007/s10096-018-03460-4
    Antimicrobial effects of local anaesthetics. Kesici Ugur,Demirci Mehmet,Kesici Sevgi International wound journal After the introduction of cocaine to the medical practice, local anaesthetics (LA) became essential in pain control. LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. This study aimed to compare the antimicrobial effects of the topical antimicrobial agent mupirocine with those of the LA lidocaine and the combination of lidocaine and adrenalin. In our study, the in vitro antimicrobial effects of 1 mL sterile saline, 20 mg/mL mupirocine, 20 mg/mL Lidocaine, and 20 mg/mL Lidocaine and Adrenaline were tested against Staphylococcus aureus American type culture collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922 as Group C (Control), Group M (Mupirocine), Group L (Lidocaine), and Group LA (Lidocaine + adrenaline), respectively. S aureus ATCC 29213, P aeruginosa ATCC 27853, and E coli ATCC 25922 were cultured onto Mueller-Hinton agar (Oxoid, UK) plates for 18 to 24 hours at 37°C. Colonies from these plates were suspended in sterile saline and a 0.5 McFarland turbidity standard suspension (corresponding to 1.5 × 10  CFU/mL) of each isolate was prepared. S Aureus ATCC 29213 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared with the group C (P ˂ 0.05). P aeruginosa ATCC 27853 inhibition zone diameter values of Group M and Group LA were significantly higher compared with the group C (P ˂ 0.05). E coli ATCC 25922 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared to the group C (P ˂ 0.05). LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. Considering that LAs show antimicrobial effects besides their analgesic effects, they may contribute to preventing the development and reducing the rate of surgical infections, decreasing the requirement to administer antibiotics. However, caution should be exercised not to antagonise the effective treatment of surgical infections, remembering that controversy on the antimicrobial effects of LAs remains in the literature. Therefore, further comprehensive studies with larger patient populations are warranted to demonstrate the antimicrobial effects of LAs. 10.1111/iwj.13153
    The impact of drugs used in anaesthesia on bacteria. Bátai I,Kerényi M,Tekeres M European journal of anaesthesiology
    Effects of Time and Storage Conditions on the Chemical and Microbiologic Stability of Diluted Buprenorphine for Injection. DenHerder Johnathan M,Reed Ralph L,Sargent Jennifer L,Bobe Gerd,Stevens Jan F,Diggs Helen E Journal of the American Association for Laboratory Animal Science : JAALAS Buprenorphine is a partial μ-opioid agonist used for analgesia. Due to the small size of laboratory rodents, buprenorphine HCl is typically diluted 10- or 20-fold with a sterile diluent, such as saline, for accurate dosing. Protocols for preparing and storing diluted buprenorphine vary by institution, and little published information is available regarding stability and beyond-use dating of specific buprenorphine preparations. The purpose of this study was to determine the chemical and microbiologic stability of diluted buprenorphine stored for a maximum of 180 d. Buprenorphine HCl was diluted 1:10 into sterile bacteriostatic saline by using aseptic technique. Diluted samples were stored in glass vials or plastic syringes, protected from light, and maintained at refrigerated or room temperature for as long as 180 d. Aerobic and anaerobic cultures on all stored samples were negative for bacterial and fungal growth. According to HPLC analysis, diluted buprenorphine stored in glass vials experienced less than 10% loss when stored for 180 d at either refrigerated or room temperature. However, the concentration of buprenorphine stored in syringes declined rapidly to more than 80% loss at room temperature and 28% loss in the refrigerator after 180 d. According to the results of this study, diluted buprenorphine stored in glass vials retains more than 90% of the initial concentration and is microbiologically stable for 180 d. However, our data suggest that, regardless of the duration, storing diluted buprenorphine in plastic syringes is inadvisable.
    INHIBITION OF BACTERIAL GROWTH BY DRUGS OF THE MORPHINE SERIES. SIMON E J Science (New York, N.Y.) The growth of Escherichia coli is reversibly inhibited by drugs of the morphine series. The order of inhibitory effectiveness for the drugs tested was levallorphan > levorphanol > dextrorphan > nalorphine > morphine. The synthetic analgesic, levorphanol, was studied in greater detail. Its effectiveness was found to be strongly dependent on the pH of the medium. Raising the pH of the medium provides a higher concentration of the neutral free base which is thought to diffuse across cell membranes more readily. However, considerations other than the rate of entry of drug into the cells must be of importance since an already established growth inhibition is promptly reversed upon lowering the pH of the medium. Two mutants of Escherichia coli with altered sensitivity to levorphanol were isolated. 10.1126/science.144.3618.543
    Levobupivacaine hydrochloride and sufentanil have no antimicrobial effect at 25 degrees C in vitro. Guillier M,Boselli E,Bouvet L,Freney J,Renaud F N R,Chassard D,Allaouchiche B European journal of anaesthesiology BACKGROUND AND OBJECTIVES:Levobupivacaine in combination with sufentanil may be used for labour or postoperative regional analgesia. The risk of bacterial growth within these contained solutions for several hours at room temperature is unknown. We investigated the in vitro antimicrobial effect of levobupivacaine and sufentanil against common micro-organisms encountered during regional anaesthesia. METHODS:Standardized suspensions of Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli were incubated for 1, 3, 6 and 24 h at 25 degrees C, with saline (as control), sufentanil 0.5 or 0.75 microg mL-1, levobupivacaine hydrochloride 5.6 mg mL-1 and concentrations of 1.4, 2.8 and 5 mg mL-1 of levobupivacaine hydrochloride with sufentanil 0.5 microg mL-1. Colony counts were compared after 24 h incubation at 37 degrees C. RESULTS:No bacterial growth was observed on any bacterial strain for any solution tested throughout the experiment. CONCLUSIONS:Our results suggest that solutions of levobupivacaine combined with sufentanil may be used for 24 h at room temperature during regional anaesthesia with no risk of bacterial growth. 10.1017/S0265021507000026
    Effects of sevoflurane and/or nitrous oxide on bacterial growth in in vitro culture conditions. Karabiyik Lale,Türkan Hülya,Ozişik Tahir,Saraçli Mehmet Ali,Haznedaroğlu Tuncer Journal of anesthesia The aim of this study was to determine the role of sevoflurane and/or nitrous oxide on bacterial growth under conditions in vitro similar to those of clinical practice. We assessed these effects on Pseudomonas aeruginosa, Acinetobacter lwoffii, and Staphylococcus aureus growth. Bacterial inoculums were prepared from reference strains in nutritive broth. Airtight chambers were filled with bacterial suspensions. Each strain was studied with and without exposure to sevoflurane and/or nitrous oxide at baseline, after 1 and 3 h. Serial dilutions and agar plates were made and the colonies were counted. P. aeruginosa were grown after exposure to the nitrous oxide alone (2.8 x 10(3) colony-forming units/ml; CFU ml(-1)) after 3 h according to the control (P < 0.05). A. lwoffii were grown after exposure to the nitrous oxide and sevoflurane with nitrous oxide (8.7 x 10(3) and 8.0 x 10(3) CFU ml(-1)) (P < 0.05), respectively. There were no changes in S. aureus growth in controls and anesthesia groups. We conclude that the effects of anesthetic agents on bacterial growth may change owing to the type of anesthetic and microorganism. 10.1007/s00540-007-0520-3
    A subanesthetic dose of sevoflurane combined with oxygen exerts bactericidal effects and prevents lung injury through the nitric oxide pathway during sepsis. Zhang Erfei,Zhao Xiaoying,Ma Huihui,Luo Dailei,Hu Yanjing,Hou Lichao,Luo Zhikai Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Volatile anesthetics have been proven to treat experimental sepsis. Sevoflurane combined with oxygen is widely applied in the clinic, and our previous study indicated that this regimen significantly reduced sepsis-induced inflammatory responses and that inhibition of NF-κB pathway activation may contribute to this protection effect. Furthermore, our previous data has shown that sevoflurane combined with oxygen has prevention effect on sepsis-induced lung injury properties and bactericidal properties, but the mechanism is not well understood. Nitric oxide (NO) has been shown to have bactericidal effects and mitigating effects on lung injury, but this is not well studied in sepsis. The present study suggested that in cecal ligation and puncture (CLP)-induced sepsis, sevoflurane combined with oxygen had bactericidal effects and reduced neutrophil infiltration into the lung, preventing inflammatory lung injury. NO production was significantly induced in peritoneal lavage fluid and bronchoalveolar lavage fluid. These effects were abolished by pharmacological inhibition of nitric oxide synthase activity. Thus, our findings suggest that sevoflurane combined with oxygen exerts bactericidal effects and prevents lung injury in sepsis through the NO pathway. 10.1016/j.biopha.2020.110169
    Sevoflurane Contamination: Water Accumulation in Sevoflurane Vaporizers Can Allow Bacterial Growth in the Vaporizer. Wallace Arthur W A & A case reports Sevoflurane vaporizers (GE Tec 7) were difficult to fill with "slow flow" and a need to "burp." Evaluation of the bottle of sevoflurane (AbbVie Ultane) demonstrated a contaminant. Four of the facilities' 13 sevoflurane vaporizers had the contaminant. Unopened sevoflurane bottles did not have evidence of contamination. The contaminant was found to be water at pH 6.0 growing Staphylococcus epidermidis. Gas chromatography revealed the production of multiple metabolites of sevoflurane, including primarily urea and 1,3,5-triazine-2,4,6(1H,3H,5H)-trione (83% and 9.6% of volatiles) in addition to multiple other organic molecules. Sevoflurane contains water that can accumulate in vaporizers allowing bacterial growth. 10.1213/XAA.0000000000000330
    Antibacterial effect of sevoflurane and isoflurane. Martínez-Serrano M,Gerónimo-Pardo M,Martínez-Monsalve A,Crespo-Sánchez M D Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia OBJECTIVE:Multidrug resistant bacteria are increasing worldwide and therapeutic options are limited. Some anaesthetics have shown antibacterial activity before. In this study, we have investigated the antibacterial effect of the halogenated anaesthetic agents sevoflurane and isoflurane against a range of resistant pathogens. METHODS:Two experiments were conducted. In the first, bacterial suspensions of both ATCC and resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were exposed to liquid sevoflurane and isoflurane during 15, 30 and 60 minutes. In the second experiment clinical resistant strains of E. coli, Klebsiella pneumoniae, Enterobacter cloacae, P. aeruginosa, Acinetobacter baumannii, S. aureus, and Enterococcus faecium were studied. Previously inoculated agar plates were irrigated with the halogenated anaesthetic agents and these were left to evaporate before the plates were incubated. In both experiments colony forming units were counted in resultant plates. RESULTS:In the first experiment, isoflurane showed faster and higher antimicrobial effect than sevoflurane against all the strains studied. Gram-negative organisms were more susceptible. In the second experiment, E. faecium was found to be resistant to both halogenated agents; only isoflurane showed statistically significant activity against the rest of the strains studied. CONCLUSIONS:Both halogenated agents, but particularly isoflurane, showed in vitro antibacterial activity against pathogens resistant to conventional antibiotics. Further investigation is required to determine whether or not they also exhibit this property in vivo. This might then allow these agents to be considered as rescue treatment against multidrug resistant pathogens, including a topical use in infected wounds.
    Topical sevoflurane for chronic venous ulcers infected by multi-drug-resistant organisms. Imbernón-Moya Adrián,Ortiz-de Frutos Francisco Javier,Sanjuan-Alvarez Mónica,Portero-Sanchez Isabel,Merinero-Palomares Raúl,Alcazar Victoria International wound journal Several anaesthetic drugs have demonstrated antibacterial properties in vitro. Anaesthetics can primarily affect the cell wall of both susceptible and multi-resistant bacteria. They may also have a synergistic effect with conventional antibiotics through an unknown mechanism. We present three cases of a chronic venous ulcer infected by multi-resistant bacteria refractory to conventional systemic antibiotics, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Treatment with topical sevoflurane was performed for 1 month without systemic antibiotics. Patients with an MRSA infection showed progressive improvement with negative culture at the end of the treatment. Multi-drug-resistant P. aeruginosa infection persisted at the end of treatment with positive culture. The local adverse events were mild and transient, including heat, pruritus and erythema. Topical sevoflurane may have an antibacterial effect on sensitive and multi-resistant strains. It can allow more complete surgical cleaning, leaving a cleaner wound with less fibrin and necrotic tissue. This decreases the bacterial colonisation and therefore the infectious risk, the bad smell and the exudation. The simultaneous use of conventional antibiotics and topical sevoflurane can have a synergistic antimicrobial effect. 10.1111/iwj.12794
    Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice. Gerber Thomas J,Fehr Valérie C O,Oliveira Suellen D S,Hu Guochang,Dull Randal,Bonini Marcelo G,Beck-Schimmer Beatrice,Minshall Richard D Anesthesiology BACKGROUND:Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. METHODS:Murine bone marrow-derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry. RESULTS:In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group. CONCLUSIONS:Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase-dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia. 10.1097/ALN.0000000000002992