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• W2063022791 abstract "Selective decontamination of the digestive tract (SDD) is a prophylactic strategy designed to prevent or minimize the impact of endogenous infections by potentially pathogenic microorganisms (PPM) in patients at high risk of infection.1 The purpose of SDD is to prevent or eradicate, if initially present, oropharyngeal and gastrointestinal carriage of PPM, especially aerobic gram-negative bacilli (AGNB), but also Staphylococcus aureus and yeasts, leaving the indigenous flora, which are thought to play a role in the resistance to colonization by PPM, predominantly undisturbed.2 The overall aim is a reduction in morbidity and mortality. SDD, selective decontamination of the digestive tract; PPM, potentially pathogenic microorganisms; AGNB, aerobic gram-negative bacilli; VRE, vancomycin-resistant enterococci; ICU, intensive care unit; RCTs, randomized controlled trials; MRSA, methicillin-resistant Staphylococcus aureus. The physiological phenomenon that the normal, mainly anaerobic flora is required to control the abnormal aerobic PPM was recognized early, after the introduction of antimicrobial agents.3 Antibiotics active against anaerobes and excreted in the gut may suppress the normal indigenous flora. They disregard the ecology and may cause candidiasis of mouth, vagina, and groin.4 These flora-suppressing antimicrobials promote yeast overgrowth, defined as ≥105 colony-forming units per milliliter of saliva and per gram of feces, following the excretion of microbiologically active antibiotic concentrations into the throat and/or gut via saliva, bile, and mucus. The need to preserve the normal indigenous flora was also acknowledged for controlling overgrowth of S. aureus5 and AGNB.6 Previous antibiotic administration lowers the infecting doses of high-level enteric pathogens Salmonella7 species and Clostridium difficile.8 More recently, overgrowth of low-level pathogens including vancomycin-resistant enterococci (VRE) is prevented by antimicrobials that respect the gut ecology.9 In 1971, van der Waaij quantified the physiological phenomenon of the normal flora controlling the abnormal flora using challenge experiments in mice.2 He defined colonization resistance as the concentration of the bacterial challenge strain expressed by the log of colony-forming units per milliliter required to result in abnormal carriage in half the animals. Generally, healthy animals possess a high colonisation resistance of >9 as they clear high doses of 109 AGNB, including Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae, contaminating their drinking water. Antimicrobials including cephradine and cefotaxime did not promote the establishment of abnormal flora and were labelled as ecology-friendly, or “green,” antibiotics.10 The abnormal carrier state was established in 50% of the animals receiving antibiotics like ampicillin and flucloxacillin after challenging them with <105 PPM. These agents decreased the resistance of mice to colonization to <5 and were considered to be “red,” as they disregard the animal gut ecology. Amoxycillin was found to be “amber,” as only high doses lowered the colonization resistance of mice. These antimicrobials were subsequently tested in healthy volunteers also in challenge studies.11-13. Vollaard demonstrated that none of the antimicrobials were found to be completely ecology friendly.13 They invariably impacted colonization resistance. He argued that the gut ecology is an extremely fragile balance and very susceptible to antimicrobial agents. However, there were still major differences among antimicrobial agents in terms of their influence on the indigenous flora. In the volunteer studies, the disregard of ampicillin and amoxycillin for the ecology was significantly worse compared with that of cephradine and cefotaxime. Abnormal carriage with ampicillin and amoxycillin was more frequent and lasted longer compared with cephradine and cefotaxime. The colonization resistance is mainly based on Clostridium species among the indigenous anaerobes.14 Ampicillin and amoxycillin are intrinsically more potent against Clostridium species compared with cephalosporins. Additionally, both antibiotics reach bactericidal concentrations in the feces following excretion via bile. This combination of factors may explain why the indigenous flora is more affected by ampicillin and amoxycillin than by cephradine and cefotaxime. The effect on colonisation resistance was argued to be an important criterion in the selection of antimicrobials. In 1969, Johanson showed that disease influences carriage, independent of antibiotic intake.15 Varying proportions of patients with chronic underlying diseases such as diabetes,15 alcoholism,16 chronic obstructive pulmonary disease17 and liver disease18 carry abnormal AGNB in the throat and gut. Two studies in patients requiring treatment on the intensive care unit (ICU) subsequently showed a correlation between abnormal AGNB and the level of illness severity.19, 20 One third of ICU patients with an acute physiology and chronic health evaluation II score ≥15 were abnormal carriers of AGNB. This amount increased to 50% in a population with an acute physiology and chronic health evaluation II score ≥27. In general, abnormal carriage develops early, within the first week of admission to ICU,21 when the patient's illness is most severe and the associated immunodepression tends to be highest. Severity of illness is the most important factor in the conversion of the “normal” into the “abnormal” carrier state, possibly due in part to increased availability of AGNB-receptor sites on the digestive tract mucosa in illness. The predominant anaerobes form a “living wallpaper” and occupy the mucosal receptor sites, inhibiting the incoming abnormal bacteria from adhering; The anaerobes “starve” the AGNB as they consume huge amounts of nutrients; The anaerobic flora produce toxic substances and volatile fatty acids to “knock out” AGNB; The anaerobic flora contribute to the clearance of abnormal bacteria via their role in promoting physiology, including motility and mucosal cell renewal. Most importantly, the healthy state implies the absence of receptors on the digestive tract mucosae for adherence of AGNB. A fibronectin layer covering the mucosal cell surface has been hypothesized to protect the host from adhering AGNB. Significantly increased levels of salivary elastase have been shown to precede AGNB carriage of the oropharynx in postoperative patients.23 It is probable that in individuals suffering both chronic and acute underlying illness, circulating populations of activated macrophages release elastase into mucosal secretions, thereby denuding the protective fibronectin layer. It is thought that this hypothetical mechanism is a deleterious consequence of the inflammatory response encountered during and after illness. Currently, the flora shift from normal to abnormal AGNB in individuals with underlying disease including liver is thought to be due to illness severity. The use of antimicrobials that impair the microbial factor of the carriage defense further promote gut contamination and overgrowth of abnormal flora.24 The most profound effects on the patient's ecology and disruption of colonization resistance have been seen with extended spectrum beta-lactam antibiotics such as amoxycillin and clavulanic acid, piperacillin and tazobactam, and ceftriaxone. Aminoglycosides have only minor effects on the indigenous gut flora. Fluoroquinolones—albeit having limited activity against anaerobes—promote yeast overgrowth.25 Elimination of fecal AGNB by intravenous ciprofloxacin lowers the rate of molecular oxygen consumption, permitting an increase in the pO2 of lumen contents from 5 to 60 mm Hg; under such conditions strictly anaerobic microorganisms can no longer survive, even though they may not themselves be sensitive to ciprofloxacin, and yeast overgrowth may subsequently develop due to an impaired microbial factor of the carriage defense. The most logical approach to minimize the risk of PPM overgrowth in the digestive tract is simple, but unfortunately it is not often given much consideration in antibiotic decision making.26 In the early 1980s Stoutenbeek et al. were the first to report successful prevention and eradication, if already present, of the abnormal carrier state, both oropharyngeal and intestinal.27 A carefully selected combination of nonabsorbable antimicrobials, polymyxin and tobramycin, was given enterally to prevent and abolish gut contamination with abnormal AGNB–i.e., to selectively decontaminate the digestive tract without affecting the indigenous flora providing colonization resistance. An enteral polyene amphotericin B or nystatin was added to control yeast overgrowth following the realization that any antibiotic, whether parenterally or enterally administered, invariably impacts the patient's ecology.13 This enteral antibiotic combination of polymyxin, tobramycin, and amphotericin B was applied to the oropharynx as a paste, gel, or lozenge and to the gastrointestinal tract as a suspension. Oral washings, rinses, and sprays failed to clear the oropharynx from AGNB due to insufficient contact time between antimicrobial and abnormal bacteria. Contact time is guaranteed by paste, gel, and lozenges, leading to effective oropharyngeal SDD within three days. For gastric and intestinal decontamination, contact time is less of an issue, as there is always a certain degree of stasis. In individuals with peristalsis, rectal AGNB carriage can be abolished within a few days, while clearance of gut AGNB may take up to a week in a patient who has had high-risk surgery and suffered subsequent impaired gut motility.28 Abnormal carrier states harm the patient. Intestinal overgrowth with AGNB causes systemic immunoparalysis.29 The reason for the administration of enteral polymyxin/tobramycin is that it promotes recovery of systemic immunity,30 and prevention or eradication of abnormal AGNB in throat and gut effectively controls migration and translocation of these PPM into the lower airways and blood, respectively.31, 32 SDD is a maneuver designed to convert the “abnormal” into the “normal” carrier state using enteral antimicrobials. Critically ill patients are unable to clear these “abnormal” pathogens due to their underlying disease. Even the new, ever more potent parenteral antimicrobials fail to clear abnormal carriage following nonlethal concentrations in saliva and feces. Fifty-four randomized controlled trials (RCTs) were designed to evaluate SDD in a total of 8,715 patients between 1987 and 2004.33 There are seven meta-analyses of RCTs assessing SDD, and all show a significant reduction in pneumonia. Five out of seven meta-analyses report a mortality reduction. The most recent meta-analysis includes 36 RCTs with 6,922 patients and shows that SDD reduces the odds ratio for pneumonia to 0.35 (95% CI, 0.29 to 0.41), and mortality to 0.78 (95% CI, 0.68 to 0.89).34 This information implies that five ICU patients need to be treated with SDD to prevent one pneumonia, and 21 ICU patients need to be treated to prevent one death. Two recent large RCTs25, 35 report an absolute mortality reduction of 8%, corresponding to the treatment of 12 patients with SDD to save one life. SDD as infection prophylaxis in liver transplantation was introduced by Wiesner et al. in 1987.36 These investigators reasoned that liver transplant recipients are the prime subset of patients to benefit from SDD prophylaxis. A high proportion of patients with liver disease carry abnormal AGNB and yeasts preoperatively. The first month posttransplantation, recipients are at high risk of AGNB and yeast infections due to surgery, mechanical ventilation, and immunosuppressive medication. Theoretically, SDD appears to be particularly applicable to the setting of liver transplantation, as the principle PPMs causing pneumonia and septicemia are the major targets of the SDD prophylaxis. The sites at which SDD is active are the likely sites from which the infecting PPM migrate into lungs and translocate into the blood. Factors that promote migration and translocation of AGNB and yeasts such as overgrowth in the throat and gut, endotracheal intubation, intestinal manipulation, absence of enteral feeding, and reduction of intestinal blood flow, typically accompany liver transplantation. Since 1987, 18 studies, including six RCTs, comprising more than 1,600 patients have been reported. An American, a Dutch, and a German liver transplant unit each performed an observational study and an RCT evaluating SDD.36-41 Safdar and colleagues elegantly appraised these data in their systematic review and meta-analysis published in this issue.42 The message is clear that severe infections such as pneumonia and septicemia due to AGNB are significantly reduced in the liver transplant recipients receiving SDD. Unfortunately, they did not separately analyze the impact of enteral polyenes on invasive fungal infections, perhaps due to the low event rate in the randomized trials. With a 10% mortality rate, it is impossible to detect a significant survival benefit in 363 randomized patients. Their analysis is in line with a previous meta-analysis by Nathens.43 However, there is a major discrepancy between these 2 meta-analyses, in that the reduction in overall infectious morbidity was no longer significant in Safdar's analysis. An attempt to explain this difference is missing. The inclusion of the most recent American and Dutch RCTs37, 39 into the meta-analysis is responsible for the reduction in the overall infection rate's becoming nonsignificant. The difference in infected patients and infection episodes was no longer significant due to a higher number of infection episodes by the low-level pathogens enterococci and coagulase-negative staphylococci. Major infections such as pneumonia and septicemia were not distinguished from minor infections, including superficial wound infections and even bile colonization diluting the net impact of SDD. Additionally, the definitions for wound and bile infections relied on vague terms, including positive culture and infected bile. Patients do not usually die of enterococcal and coagulase-negative staphylococcal contamination of the T-tube, but they do generally succumb because of pseudomonal and fungal sepsis. These invasive infections were completely prevented by SDD in both recent RCTs. Finally, the researchers' previous observational studies showed infection rates of 23.3% and 45%, in 1987 and 1990, respectively.36, 38 In spite of major improvements such as refinement in surgical techniques and advent of modern immunosuppressive agents, these infection rates increased to 32.4% and 84.5% in the American and Dutch transplant units, respectively, invariably due to the perceived enterococcal and coagulase-negative staphylococcal problem.37, 39 Similarly, the German group reports a dramatic increase in infection rates, from 27.8% to 48%, in their recent RCT41 compared to the observational study of one decade ago.40 Half of all infections were due to enterococci and coagulase-negative staphylococci causing pneumonia and cholangitis in the patients receiving SDD. Pneumonia due to these low-level pathogens is rare. The analysis of the available data on patients infected with resistant microorganisms by Safdar is at best vague and at worst nonexistent. All seven studies providing information on resistance explicitly report that there were no infections due to resistant AGNB. This finding is in line with the results of the most recent meta-analysis on SDD of 36 RCTs conducted over 17 years showing that antibiotic resistance was not a clinical problem.34 The latest RCT, evaluating SDD in about 1,000 patients requiring treatment in ICU, had significantly fewer carriers of multiresistant AGNB in patients receiving SDD than in the control group.35 One should remember that the principal aim of SDD is the selective eradication of both oropharyngeal and gastrointestinal carriage of abnormal AGNB. Thus, SDD not only eliminates a prime source of endogenous infection but also profoundly influences the balance of forces associated with the emergence of resistance. In principle, the enteral agents polymyxin and tobramycin must exert considerable selective pressure for resistance. However, the combination of very high enteral bactericidal antibiotic levels in saliva and feces, the use of synergistic antibiotic mixtures, and the maintenance of colonization resistance create a unique environment that has proven strikingly successful in preventing overgrowth of resistant mutants among the target microorganisms. One trial using historical controls reports that of 212 SDD patients, 14 (6%) had methicillin-resistant Staphylococcus aureus (MRSA) infections, while in the control group, 11 (7%) of the 157 patients receiving only systemic antibiotics developed MRSA infections.44 SDD, by design, is not active against MRSA. Proponents of SDD have always accepted this possibility and proposed microbiological surveillance of throat and rectal swabs to allow early detection of MRSA carriage. Under these circumstances SDD requires the addition of oropharyngeal and gastro-intestinal enteral vancomycin. Two studies using 2 g of a 4% vancomycin gel or paste and 2 g of vancomycin solution added to the nonabsorbable polymyxin, tobramycin, and amphotericin B demonstrated the prevention and the eradication of carriage and overgrowth of abnormal MRSA.45, 46 Subsequent MRSA infection, transmission, and outbreaks were controlled. Enteral vancomycin has not been shown to select S. aureus with reduced sensitivity to vancomycin or VRE.45, 46 A total of seven SDD studies, three of them in liver transplant recipients, report VRE data.37, 44-49 The incidence of both carriage and infection due to VRE was low and similar in test and control groups in the two American RCTs.37, 47 Remarkably, the infection rate was significantly higher in the historical control group compared with the transplant group receiving SDD.44 The concern that SDD promotes VRE carriage and infection has been investigated in four ICU studies.45, 46, 48, 49 An American study, conducted in a unit with a low incidence of VRE infection, reports that oral SDD did not increase the incidence of VRE carriage and infection.48 SDD, combined with enteral vancomycin throughout the treatment in ICU, was evaluated in one Spanish46 and two Italian studies.45, 49 Despite VRE being imported into the Spanish unit, no change in the use of enteral vancomycin and polymyxin, tobramycin, and amphotericin B was required, as rapid and extensive spread did not occur over four years.46 VRE was not isolated in the Italian trials, one of which was randomized and controlled.45, 49 In conclusion, enteral polymyxin, tobramycin, and amphotericin B combined with a short preoperative prophylaxis with parenteral cefotaxime as originally proposed by Wiesner et al. has been shown to be an effective and safe protocol in patients receiving a liver transplant. It is also the approach that leaves the patient's gut ecology as undisturbed as possible. The three latest RTCs (35,37,47) have used poor definitions for minor infections due to enterococci and coagulase-negative staphylococci, only to dilute the significant reduction in severe infections due to AGNB, S. aureus, and yeasts achieved by SDD. However, that type of analytical method does not justify their recommendations to abandon SDD as prophylaxis in liver transplantation.50 The authors thank Mrs. Lynda Jones for meticulously typing the manuscript." @default.
• W2063022791 created "2016-06-24" @default.
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• W2063022791 modified "2023-09-23" @default.
• W2063022791 title "Selective decontamination of the digestive tract: Rationale behind evidence-based use in liver transplantation" @default.
• W2063022791 cites W1583991068 @default.
• W2063022791 cites W1607940879 @default.
• W2063022791 cites W1964712896 @default.
• W2063022791 cites W1965143457 @default.
• W2063022791 cites W1966319911 @default.
• W2063022791 cites W1970936978 @default.
• W2063022791 cites W1975698525 @default.
• W2063022791 cites W1975830627 @default.
• W2063022791 cites W1982839041 @default.
• W2063022791 cites W1984727640 @default.
• W2063022791 cites W1984731911 @default.
• W2063022791 cites W1985869897 @default.
• W2063022791 cites W1989230683 @default.
• W2063022791 cites W2000902780 @default.
• W2063022791 cites W2005689781 @default.
• W2063022791 cites W2027502096 @default.
• W2063022791 cites W2041542881 @default.
• W2063022791 cites W2055306795 @default.
• W2063022791 cites W2057600916 @default.
• W2063022791 cites W2059386369 @default.
• W2063022791 cites W2060935540 @default.
• W2063022791 cites W2063516640 @default.
• W2063022791 cites W2074962340 @default.
• W2063022791 cites W2075620078 @default.
• W2063022791 cites W2085293664 @default.
• W2063022791 cites W2089367665 @default.
• W2063022791 cites W2095923402 @default.
• W2063022791 cites W2096070973 @default.
• W2063022791 cites W2097977391 @default.
• W2063022791 cites W2120503702 @default.
• W2063022791 cites W2122818484 @default.
• W2063022791 cites W2123797220 @default.
• W2063022791 cites W2130163668 @default.
• W2063022791 cites W2135801231 @default.
• W2063022791 cites W2149434106 @default.
• W2063022791 cites W2158956030 @default.
• W2063022791 cites W2159161102 @default.
• W2063022791 cites W2166450614 @default.
• W2063022791 cites W2257654803 @default.
• W2063022791 cites W2322361714 @default.
• W2063022791 cites W4230207194 @default.
• W2063022791 cites W4244498169 @default.
• W2063022791 cites W4246327236 @default.
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