Nonabsorbable Antimicrobials Research Articles

772. Effect of Selective Digestive Decontamination Using Oral Colistin on HAI Rates and All-Cause Mortality Among Cardiovascular Surgery Patients - A Single Centre Experience from India

BackgroundHospital acquired infections affect the morbidity and mortality of ICU patients considerably. Selective digestive decontamination (SDD) is defined as the prophylactic application of topical, non-absorbable antimicrobials in the oropharynx and stomach, with the goal of eradicating potentially pathogenic microorganisms but preserving the protective anaerobic microbiota. SDD has been applied in trials among critically ill patients and found to be effective in reducing HAI. MethodsThis cohort study was conducted in our cardiothoracic vascular surgery ICU of a tertiary care hospital, where patients were given oral colistin syrup (100mg 6th hourly for 5 days) in the immediate post op during the intervention period. We compared the clinical and microbiological outcomes of patients before (5 months, pre-intervention arm) and after (5 months, intervention arm) the implementation of SDD (Oral colistin syrup).ResultsA total of 78 patients were included in the interventional arm with a mean age of 58.7 years whereas the pre-interventional group consisted of 94 study participants with a median age of 57.5 years. 11 out of 94 had positive respiratory sample culture (11.7%) in the preintervention group which mandated antibiotic therapy for HAP compared to one culture positive in the interventional period (OR 0.0980, 95% CI: 0.0124 to 0.777 and P=0.0279). One patient had blood stream infection in the pre-intervention period compared to none in the intervention phase. All-cause mortality in the pre-interventional group was 7.44% (7 in 94) vs 1.28% (1 in 78) in the interventional group (OR 0.1614, 95% CI: 0.0194 to 1.3416, P= 0.0914). Adverse events (nausea, vomiting & loose stools) were observed in a total of 24 study patients, but necessitated withdrawal of regimen only in nine patients.ConclusionAn SDD regimen of Colistin alone in Cardiac Surgery patients resulted in statistically significant reduction in incidence of Hospital Acquired Pneumonia, along with a reduction in all-cause mortality (though not statistically significant). Disclosures All Authors: No reported disclosures

Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis

Many meta-analyses have shown reductions in infection rates and mortality associated with the use of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) in intensive care units (ICUs). These interventions have not been widely implemented because of concerns that their use could lead to the development of antimicrobial resistance in pathogens. We aimed to assess the effect of SDD and SOD on antimicrobial resistance rates in patients in ICUs. We did a systematic review of the effect of SDD and SOD on the rates of colonisation or infection with antimicrobial-resistant pathogens in patients who were critically ill. We searched for studies using Medline, Embase, and Cochrane databases, with no limits by language, date of publication, study design, or study quality. We included all studies of selective decontamination that involved prophylactic application of topical non-absorbable antimicrobials to the stomach or oropharynx of patients in ICUs, with or without additional systemic antimicrobials. We excluded studies of interventions that used only antiseptic or biocide agents such as chlorhexidine, unless antimicrobials were also included in the regimen. We used the Mantel-Haenszel model with random effects to calculate pooled odds ratios. We analysed 64 unique studies of SDD and SOD in ICUs, of which 47 were randomised controlled trials and 35 included data for the detection of antimicrobial resistance. When comparing data for patients in intervention groups (those who received SDD or SOD) versus data for those in control groups (who received no intervention), we identified no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1·46, 95% CI 0·90-2·37) and vancomycin-resistant enterococci (0·63, 0·39-1·02). Among Gram-negative bacilli, we detected no difference in aminoglycoside-resistance (0·73, 0·51-1·05) or fluoroquinolone-resistance (0·52, 0·16-1·68), but we did detect a reduction in polymyxin-resistant Gram-negative bacilli (0·58, 0·46-0·72) and third-generation cephalosporin-resistant Gram-negative bacilli (0·33, 0·20-0·52) in recipients of selective decontamination compared with those who received no intervention. We detected no relation between the use of SDD or SOD and the development of antimicrobial-resistance in pathogens in patients in the ICU, suggesting that the perceived risk of long-term harm related to selective decontamination cannot be justified by available data. However, our study indicates that the effect of decontamination on ICU-level antimicrobial resistance rates is understudied. We recommend that future research includes a non-crossover, cluster randomised controlled trial to assess long-term ICU-level changes in resistance rates. None.

Covering the Cover

Covering the Cover

The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice

Alterations in the microbial composition of the gastrointestinal tract (dysbiosis) are believed to contribute to inflammatory and functional bowel disorders and psychiatric comorbidities. We examined whether the intestinal microbiota affects behavior and brain biochemistry in mice. Specific pathogen-free (SPF) BALB/c mice, with or without subdiaphragmatic vagotomy or chemical sympathectomy, or germ-free BALB/c mice received a mixture of nonabsorbable antimicrobials (neomycin, bacitracin, and pimaricin) in their drinking water for 7 days. Germ-free BALB/c and NIH Swiss mice were colonized with microbiota from SPF NIH Swiss or BALB/c mice. Behavior was evaluated using step-down and light preference tests. Gastrointestinal microbiota were assessed using denaturing gradient gel electrophoresis and sequencing. Gut samples were analyzed by histologic, myeloperoxidase, and cytokine analyses; levels of serotonin, noradrenaline, dopamine, and brain-derived neurotropic factor (BDNF) were assessed by enzyme-linked immunosorbent assay. Administration of oral antimicrobials to SPF mice transiently altered the composition of the microbiota and increased exploratory behavior and hippocampal expression of BDNF. These changes were independent of inflammatory activity, changes in levels of gastrointestinal neurotransmitters, and vagal or sympathetic integrity. Intraperitoneal administration of antimicrobials to SPF mice or oral administration to germ-free mice did not affect behavior. Colonization of germ-free BALB/c mice with microbiota from NIH Swiss mice increased exploratory behavior and hippocampal levels of BDNF, whereas colonization of germ-free NIH Swiss mice with BALB/c microbiota reduced exploratory behavior. The intestinal microbiota influences brain chemistry and behavior independently of the autonomic nervous system, gastrointestinal-specific neurotransmitters, or inflammation. Intestinal dysbiosis might contribute to psychiatric disorders in patients with bowel disorders.

Intensive Care Decontamination Protocols Raise Resistance Rates

“Selective decontamination” of the digestive tract (SDD) and the oropharynx (SOD) are techniques in which nonabsorbable antimicrobials are used to reduce bacterial colonization in patients who are at risk for infection. Several studies have confirmed that these interventions, when used routinely in intensive care unit (ICU) patients along with empirical parenteral antibiotics, lower the incidence …

NICE/NPSA Patient Safety Pilot

NICE/NPSA Patient Safety Pilot

HLA Identical Hematopoietic Stem Cell Transplantation for Acute Leukemia in Children - A Single Center Experience.

Between 1980 and 2002, 132 children and adolescents (median age 8.5 years, range 1.1 to 17.3) got an allogeneic HLA-identical hematopoietic stem cell transplantation (SCT) from a sibling donor for acute leukemia. The patients suffered from ALL in 1st remission (n=24), ALL in 2nd remission (n=53) and AML in 1st remission (n=55). The mean follow-up time after SCT was 11.5 years (range 1.3 to 23.3 years). The source of the stem cells was bone marrow in all but 3 cases of cord blood-derived stem cells. The number of nucleated marrow cells in the graft varied between 0.5 and 6.8x108/kg (median 2.75x108/kg). Most patients, 118 of 132, were pre-treated with a total body irradiation (TBI) and cyclophosphamide-based regimen. TBI doses were 1x 7 Gy for children of 3 and 4 years, 1x 7.5 Gy for >4 and <10 years, and 1x 8 Gy (before 1990) and 2x 6 Gy on two consecutive days (after 1990) for children older than 10 years. Initially, graft-versus-host disease (GvHD) prophylaxis consisted of long-course methotrexate (MTX) only (n=24), later a short-course MTX-Cyclosporine A prophylaxis was given (n=102). All patients were nursed in strict protective isolation, using positive-pressure laminar-air flow cubicles or rooms, and got total gut decontamination with non-absorbable antimicrobials. Engraftment, transplant-related complications, relapse of the disease and survival were evaluated retrospectively in relation to disease- and transplant-related characteristics. None of the patients failed to engraft. The mean 5-year probability of overall survival was 63%, 53% and 74% for ALL1, ALL2 and AML1 patients, respectively. Transplant-related mortality was 6%. The incidence of acute GvHD in evaluable cases was 17% (21/124), of whom 7 (6%) got grade II to IV. Chronic GvHD occurred in 10 patients out of 125 evaluable patients (8%). The mean 5-year probability of relapse was 35%, 49% and 26% for ALL1, ALL2, and AML1 patients, respectively. Most relapses (70%) occurred within the first year post-SCT. The patient age and dose of TBI were significantly related with post-transplant relapse (p=0.007). Overall survival was significantly higher in children that received a higher dose of TBI (see figure). Overall, acute GvHD was not significantly associated with relapse, but none of the AML patients (n=9) with acute GvHD got a relapse (likelihood ratio test, p=0.02), which was not the case for ALL first or second remission patients. This retrospective single-center study on HLA-identical SCT for acute leukemia in 132 consecutively enrolled children confirms the beneficial role of slight to moderate acute GvHD in the suppression of relapse of AML, and draws attention to the potential antileukemia effect of a high (fractionated) dose of TBI in the conditioning. [Display omitted]

Can Topical and Nonabsorbable Antimicrobials Prevent Cross-Transmission of Resistant Strains in ICUs?

Can Topical and Nonabsorbable Antimicrobials Prevent Cross-Transmission of Resistant Strains in ICUs?

Infection control in critically ill patients: Effects of selective decontamination of the digestive tract

The use of selective decontamination of the digestive tract (SDD) to control infection in the intensive care unit (ICU) is reviewed. There are three basic patterns of infection in the ICU: primary endogenous, secondary endogenous, and exogenous. In exogenous infection, no microbial carriage precedes colonization and infection. In endogenous infection, infection is preceded by oropharyngeal or GI carriage. A primary endogenous infection is caused by an organism carried by the patient on admission to the ICU, whereas a secondary endogenous infection is caused by organisms acquired in the ICU. The traditional approach to infection control in the ICU has included frequent hand washing, limiting the use of agents for prophylaxis of stress-ulcer bleeding, and limiting the use of injectable antimicrobials to the treatment of infection in order to prevent resistance. The recognition that hand washing only partially reduces endogenous infection led to the use of nonabsorbable antimicrobials to abolish oropharyngeal and gastrointestinal carriage of potentially pathogenic microorganisms. In addition, the use of an injectable antimicrobial during the first four days in the ICU to control primary endogenous infection was considered not to lead to resistance as long as it was combined with nonabsorbable antimicrobials. Of 41 fully reported clinical trials of SDD, 33 showed a significant reduction of infectious morbidity among patients who received SDD. Of the 32 trials in which carriage of potential pathogens was a measured endpoint, 31 showed a reduction in carriage. Of the 24 studies in which resistance was an endpoint, 22 showed no increase in resistance associated with SDD. Only 10 of 35 trials that examined death showed a significant decrease in mortality. SDD, used in conjunction with traditional infection-control measures, diminishes microbial carriage and infectious morbidity in the ICU without increasing antimicrobial resistance.

The place of selective decontamination in intensive care

Selective decontamination of the digestive tract means the abolition of the oropharyngeal and gastrointestinal carriage of only disease-causing microorganisms. The abolition of the carrier state by topical, non-absorbable antimicrobials (polymyxin E, tobramycin, amphotericin B) is associated with clinical (prevention of secondary endogenous infections), bacteriological (control of resistance) and epidemiological (outbreak control) benefits. The 22 trials published so far are reviewed and discussed.

Pilot Trial of Selective Decontamination for Prevention of Bacterial Infection in an Intensive Care Unit

Selective decontamination of the oropharynx and gastrointestinal tract with nonabsorbable antimicrobials and sucralfate, a stress ulcer prophylactic that maintains the normal gastric acid bacterial barrier, were compared for prevention of pneumonia in a cardiac surgery intensive care unit. Over 8 months, 51 patients received selective decontamination and 56 received sucralfate. The selective decontamination regimen included polymyxin, gentamicin, and nystatin given as an oral paste and as a solution; patients also received standard antacid or histamine2 blocker stress ulcer prophylaxis. Patients in the selective decontamination group had significantly less colonization of the oropharynx and stomach by gram-negative bacilli (12% vs. 55%, P less than .001), significantly fewer infections due to gram-negative bacilli (6% vs. 20%, P = .02), and fewer infections overall (12% vs. 27%, P = .04). There was one episode of pneumonia in the selective decontamination group and five in the sucralfate group. Mortality and length of stay did not differ between the groups, but those receiving selective decontamination had less than one-third as many days of systemic antibiotic therapy with no increase in colonization or infection with resistant gram-negative bacilli. Thus, selective decontamination appeared to reduce both extrapulmonary and pulmonary infections.