Triple Regimen of Selective Decontamination of the Digestive Tract, Systemic Cefotaxime, and Microbiological Surveillance for Prevention of Acquired Infection in Intensive Care

Ledingham, I. McA.; Eastaway, AnneT.; McKay, I C; Alcock, S. R.; McDonald, J.C.; Ramsay, Graham

doi:10.1016/s0140-6736(88)91656-x

Cited by 283 publications

(54 citation statements)

References 28 publications

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“…This disappointing microbiological result contrasts strongly with the use of the same antibacterials applied as a gel or paste to the buccal mucosa in intensive care patients, when AGNB populations are drastically reduced within 3 -4 days (Stoutenbeek et al, 1984;Ledingham et al, 1988). The striking success of the latter regimens may well reflect prolonged drug exposure of mucosal organisms resulting from the adherent gel or paste preparations used.…”

Section: Methodsmentioning

confidence: 97%

The reduction of radiation mucositis by selective decontamination antibiotic pastilles: a placebo-controlled double-blind trial

Symonds

McIlroy²,

Khorrami³

et al. 1996

Br J Cancer

109

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Summary The aim of this study was to see if antibiotic pastilles could reduce radiation mucositis, pain, dysphagia and weight loss in patients undergoing radical radiotherapy for head and neck cancer. A total of 275 patients with T -T4 tumours entered the study; 136 were allocated to suck four times daily a pastille containing amphotericin, polymyxin and tobramycin. The During treatment, cells in the basal layers of the mucous membranes within the irradiated volume are unable to replace adequately cells lost through inactivation or exfoliation. The resultant mucosal damage may then be exacerbated by colonisation of the affected area by abnormal microbial flora. Mucositis has a number of manifestations that may be seen at different times depending on the volume irradiated, the total dose and the fractionation schedule. Initially, there may be a transient white discolouration, followed by deepening erythema and later a white pseudomembrane which may be patchy or confluent. The most severe manifestation is ulceration of the mucosa.In health, the very diverse oropharyngeal flora contains a marked preponderance of anaerobic bacteria together with a near universal presence of lesser numbers of viridans streptococci and Neisseria species. Irradiation, local tumour and surgery can all interfere with the mucosal defences important for the maintenance of this ecological balance. In consequence, there is frequent overgrowth of organisms rarely seen in health and then only at low concentrations. Overgrowth of yeasts and aerobic Gram-negative bacilli (in particular Enterobacteriaceae, Pseudomonads and Acinetobacter) has attracted particular attention in the context of irradiation mucositis (van Saene and Martin, 1990).There are no established effective measures to prevent or treat mucositis. Standard therapy is to maintain good oral hygiene and prescribe analgesics if necessary. A small study by Spijkervert et al. (1991) described a novel approach to this problem. Lozenges containing polymyxin E, tobramycin and amphotericin B were used to eradicate selectively aerobic Gram-negative bacteria (AGNB) and yeasts from the oropharynx while retaining the normal anaerobic and aerobic flora. This selective decontamination regimen was given to 15 patients with head and neck cancer treated by radiotherapy. An excellent microbiological result was obtained and mucositis was confined to erythema in all patients. By contrast, matched historical controls treated with a placebo or chlorhexidene showed an 80% incidence of more severe mucositis with pseudomembrane formation.The aim of the study was to use a placebo-controlled double-blind trial to test the hypothesis that the more severe forms of irradiation mucositis are associated with abnormal carriage of AGNB and yeasts and that selective reduction of these microbial populations with non-absorbable antibiotics would reduce both the signs and symptoms of mucositis. Materials and methodsPatients receiving potentially curative radiotherapy for T-4 head and neck cancer were entered into th...

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Section: Methodsmentioning

confidence: 97%

The reduction of radiation mucositis by selective decontamination antibiotic pastilles: a placebo-controlled double-blind trial

Symonds

McIlroy²,

Khorrami³

et al. 1996

Br J Cancer

109

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“…Nosocomial pneumonia presents a particular problem, especially in patients requiring assisted ventilation. In such patients colonization of the oropharynx with multiresistant hospital pathogens can lead, in the absence of mechanical or local defences, to a very high incidence of nosocomial pneumonia, as shown in several recent studies (Stoutenbeek et al, 1987;Ledingham et al, 1988). Aerobic Gram-positive or Gram-negative bacterial pathogens are the most common causative agents.…”

Section: Introductionmentioning

confidence: 99%

Monotherapy in serious hospital-acquired infections: a clinical trial of ceftazidime versus imipenem/cilastatin

Norrby

Finch

Glauser

1993

J Antimicrob Chemother

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The clinical and bacteriological efficacy and safety of the antibiotics ceftazidime or imipenem/cilastatin in seriously ill patients with nosocomial infections were compared in a prospective, open, evaluator-blind, multicentre comparative trial. The study was performed in 26 European centres, the majority being intensive care units. Subjects were randomized to receive either ceftazidime 2 g bid or imipenem cilastatin 0-5 g qid given for at least five days after stratification for pneumonia, septicaemia or urinary tract infection (UTI). Three hundred and ninety-three patients with serious nosocomial infections (254 with pneumonia; 91 with septicaemia and 48 UTI were treated between February 1988 and January 1990 and their clinical and bacteriological response to antibiotic treatment assessed. There were no significant differences between ceftazidime and imipenem/cilastatin in clinical efficacy. The failure rates in evaluable patients were 22 and 26% in pneumonia, 23 and 19% in septicaemia and 0 and 5% respectively in those with UTI. Overall there was no significant difference between the two antibiotics for bacteriological response in the three infection strata. However, in patients with pneumonia ceftazidime was significantly more effective than imipenem/cilastatin in clearing patients of

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“…In most instances, colonization of the gastrointestinal and respiratory tracts with pathogenic gramnegative bacteria precedes the development of infection in these patients. As an approach to prevent this progression from colonization through infection, the use of topical nonabsorbable antibiotics to selectively decontaminate the digestive tract (SDD) has been evaluated in 14 studies with historic controls (7,18,21,23,31,33,36,37,50,(52)(53)(54)63) and 26 studies with concurrent controls (1, 3, 4, 7, 9, 10, 15, 19, 22, 25, 27, 29, 32, 38, 42, 44-46, 49, 54-56, 58, 63, 65).A meta-analysis based on 22 randomized studies (4,142 patients) reported convincing evidence of a favorable effect of SDD on the incidence of respiratory infection (RI) with a reduction of approximately 63% (51). There may also be a difference in mortality as great as 20%, but this was shown to be statistically significant only when three studies (25,46,54) which had failed specific inclusion criteria for this meta-analysis were subsequently included.…”

mentioning

confidence: 99%

Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection?

Hurley

1995

Antimicrob Agents Chemother

110

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Selective decontamination of the digestive tract (SDD) has been evaluated as a method to prevent colonization and infection in ventilated patients in 40 trials. On the basis of an assumption that cross-infection would be reduced as a consequence of SDD and that this would distort the results of SDD studies that used concurrent controls, 14 studies used historic controls. To test this assumption, three observations from the two types of studies were compared. (i) The differences between observed and expected event rates for each study were used to perform a meta-analysis. This revealed that the summary odds ratios for bacteremia and respiratory infection were marked by significant heterogeneity (P > 0.95) and inconsistencies between those derived from studies with concurrent versus studies with historic controls. (ii) Where the data were available, the rates of acquisition of colonization in control groups were higher in studies with concurrent controls than in studies with historic controls. (iii) At least four studies with concurrent controls have shown a pattern of pathogenic isolates consistent with cross-infection between groups. These results are contrary to the initial assumption and suggest the possibility that SDD represents a major cross-infection hazard.Colonization and infection with gram-negative bacteria occur commonly in patients requiring prolonged intubation in intensive care units (ICUs) (12,20,62). Moreover, pneumonia is the most common fatal nosocomial infection, with mortality rates of 20 to 50% (12). In most instances, colonization of the gastrointestinal and respiratory tracts with pathogenic gramnegative bacteria precedes the development of infection in these patients. As an approach to prevent this progression from colonization through infection, the use of topical nonabsorbable antibiotics to selectively decontaminate the digestive tract (SDD) has been evaluated in 14 studies with historic controls (7,18,21,23,31,33,36,37,50,(52)(53)(54)63) and 26 studies with concurrent controls (1, 3, 4, 7, 9, 10, 15, 19, 22, 25, 27, 29, 32, 38, 42, 44-46, 49, 54-56, 58, 63, 65).A meta-analysis based on 22 randomized studies (4,142 patients) reported convincing evidence of a favorable effect of SDD on the incidence of respiratory infection (RI) with a reduction of approximately 63% (51). There may also be a difference in mortality as great as 20%, but this was shown to be statistically significant only when three studies (25,46,54) which had failed specific inclusion criteria for this meta-analysis were subsequently included. A criticism of this meta-analysis is that it failed to address the striking variability in RI rates in the control groups. In general, these rates were high (Ͼ40%) in studies in which a beneficial effect had been shown in contrast to studies that had not shown a beneficial effect (5).The interpretation of these studies is controversial (30,34,57,59,61). Issues of patient mix, study size, and design have been considered. In these studies, observer blinding is inherently difficult ...

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Triple Regimen of Selective Decontamination of the Digestive Tract, Systemic Cefotaxime, and Microbiological Surveillance for Prevention of Acquired Infection in Intensive Care

Cited by 283 publications

References 28 publications

The reduction of radiation mucositis by selective decontamination antibiotic pastilles: a placebo-controlled double-blind trial

The reduction of radiation mucositis by selective decontamination antibiotic pastilles: a placebo-controlled double-blind trial

Monotherapy in serious hospital-acquired infections: a clinical trial of ceftazidime versus imipenem/cilastatin

Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection?

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