Optimizing decision-making among childcare staff on fever and common infections: cluster randomized controlled trial.

BACKGROUND: Children 0-4 years attending childcare are more prone to acquire infections than home-cared children. Childcare illness absenteeism due to fever is mostly driven by fear towards fever in childcare staff and parents. This may cause high childcare absenteeism, healthcare service use, and work absenteeism in parents. This study evaluates a multicomponent intervention targeting determinants of decision-making among childcare staff on illness absenteeism due to fever and common infections. METHODS: The multicomponent intervention was developed based on the Intervention Mapping approach and consisted of (i) an educational session, (ii) a decision tool, (iii) an information booklet and (iv) an online video. The intervention was evaluated in a cluster randomized controlled trial in Southern Netherlands. Nine centres received the intervention and nine provided childcare-as-usual. Primary outcome measure was the percentage of illness absenteeism on cluster level, defined as number of childcare days absent due to illness on total of registered childcare contract days in a 12-week period. Secondary outcome measures included intended behaviour, attitude, risk perception, knowledge and self-efficacy of childcare staff. Outcomes were analyzed using linear mixed models accounting for clustering. Knowledge was descriptively analysed. RESULTS: Overall illness absenteeism was comparable in intervention (2.95%) and control group (2.52%). Secondary outcomes showed significant improvements in intervention group regarding intended behaviour, two of three attitude dimensions. Knowledge increased compared with control but no differences regarding self-efficacy. CONCLUSION: The intervention was not effective in reducing illness absenteeism. However, the intervention improved determinants of decision-making such as intended behaviour, attitude, and knowledge on fever. TRIAL REGISTRATION: NTR6402 (registered on 21 April 2017).

Optimising decision making on illness absenteeism due to fever and common infections within childcare centres: development of a multicomponent intervention and study protocol of a cluster randomised controlled trial.

BACKGROUND: Evidence has shown that children 0-4 year-old attending childcare are prone to acquire infections compared to children cared for at home, with fever being the most common symptom. Illness absenteeism due to fever and common infections is substantial and mostly driven by unrealistic concerns and negative attitude towards fever of both childcare staff and parents, resulting in illness absenteeism from childcare, work absenteeism among parents and healthcare service use. The objective of this study is to optimise decision making among childcare staff on illness absenteeism due to fever and common infections in childcare. Underlying determinants of behavioural change were targeted by means of a multicomponent intervention. METHODS: A multicomponent intervention was developed to improve decision making, using the stepwise approach of Intervention Mapping, and in close collaboration with stakeholders and experts. The intervention consisted of 1) a two-hour educational session on fever among childcare staff; 2) an online video for childcare staff and parents emphasising key information of the educational session; 3) a decision tool for childcare staff and parents in the format of a traffic light system to estimate the severity of illness and corresponding advices for childcare staff and parents; 4) an information booklet regarding childhood fever, common infections, and self-management strategies for childcare staff and parents. The multicomponent intervention will be evaluated in a cluster randomised trial with a 12-week follow-up period and absenteeism due to illness (defined as the percentage of childcare days absent due to illness on the total of childcare days during a 12-week period) as primary outcome measure. Secondary outcome measures are: incidence rate and duration of illness episodes, knowledge, attitude, self-efficacy, and risk perception on fever and common infections of childcare staff and parents, healthcare service use in general and paracetamol use, and work absenteeism of parents. DISCUSSION: This study aims to develop a multicomponent intervention and to evaluate to what extent illness absenteeism due to fever and common infections can be affected by implementing a multicomponent intervention addressing decision making and underlying determinants among childcare staff and parents of children attending daycare. TRIAL REGISTRATION: NTR6402 (registered on 21-apr-2017).

Liposomal cefoxitin in a porcine model of intra-abdominal sepsis: hemodynamic changes.

The effects of free versus liposomal cefoxitin on various physiological parameters in a porcine model of Gram-negative intra-abdominal sepsis were evaluated. Four different doses of Escherichia coli inoculum mixed with sterile pig feces were used (10(8), 10(9), 10(10), and 10(11) cfu/animal), and the most consistent hemodynamic changes were observed with an inoculum of approximately 10(11) bacteria/20 kg animal. Two treatment groups were established as follows: free cefoxitin (n = 9) and liposomal cefoxitin (n = 9). All animals were maintained under anesthesia for the duration of the study, and then euthanized 24 h following intra-abdominal inoculation. The inoculated and nontreated animals showed increases in heart rate, mean pulmonary arterial pressure, systemic and pulmonary vascular resistance, and decreases in mean systemic arterial pressure and cardiac index. These changes were significant (p < .05) compared with a control group injected with normal saline. Liposomal cefoxitin-treated animals showed significantly lower decreases in mean systemic arterial pressure and increases in heart rate (p < .05) compared with both the inoculated nontreated and free cefoxitin-treated groups. Both liposomal and free cefoxitin significantly modulated the mean pulmonary arterial pressure compared with the inoculated nontreated animals (p < .05). Acidosis that developed during intra-abdominal infection diminished 6 h following the first dose of liposomal cefoxitin (p < .05). The results of these experiments demonstrate that liposomal cefoxitin exerts a beneficial modulation of some of the hemodynamic disturbances during intra-abdominal Gram-negative sepsis.

Deferoxamine induces hypotension in experimental gram-negative septicemia.

Multiple organ system failure may result from tissue damage caused by activated neutrophils or endotoxin. A significant part of this tissue damage is due to peroxidation induced by oxygen-free radicals and requires iron as a co-factor. Iron chelation has been shown to prevent tissue damage in some models. This experiment was carried out to determine whether iron chelation with deferoxamine (DFO) would prevent lung damage in a swine model of Gram-negative septicemia. Fifteen animals were randomized to control, Pseudomonas aeruginosa infusion at a rate of 2 x 10(7) colony forming units/20 kg/min (septic group), or Pseudomonas infusion combined with DFO pretreatment at a dose of 80 mg/kg/h (septic-treated group). Three of six septic-treated animals became severely hypotensive and died during the course of the experiment as opposed to none of six septic animals. Surviving septic-treated animals were significantly hypotensive (60 +/- 24 mmHg mean arterial pressure) compared to septic (122 +/- 9 mmHg) and control (109 +/- 8 mmHg) animals. DFO did not improve respiratory function (e.g., pO2) or morphology in septic animals. We conclude that iron-chelation therapy with DFO at the above dosage results in a significant deterioration in cardiovascular function in septic swine. Lung damage was not prevented.

Liposomal cefoxitin in a porcine model of intra-abdominal sepsis: bactericidal efficacy.

The bactericidal effect of free versus liposomal cefoxitin was evaluated in the major reticuloendothelial organs in a porcine model of intra-abdominal sepsis. Yorkshire Landrace pigs were inoculated with 3.2 x 10(10) (n = 5) or 1.4 x 10(11) (n = 7) cfu of Escherichia coli mixed in sterile feces/animal. Two treatment groups inoculated with 1.4 x 10(11) cfu were established: free cefoxitin (n = 9) and liposomal cefoxitin (n = 9). All animals were maintained under anesthesia and euthanized after 24 h. The number of E. coli recovered in the liver, lungs, and spleen was significantly affected by inoculum size (p < .05). The liver had significantly higher numbers of bacteria (p < .05) compared with the other organs, regardless of the inoculum size. The liver and the lung of the liposomal cefoxitin-treated group showed significantly lower numbers of E. coli (5.0 x 10(4) and 6.3 x 10(2), respectively) compared with the untreated (liver, 6.3 x 10(7); lung, 2.0 x 10(6)) and free cefoxitin (liver, 5.0 x 10(6); lung, 7.9 x 10(4))-treated groups (p < .05). At 2 h following the injection of free and liposomal cefoxitin, the decrease of E. coli in peritoneal fluid compared with the nontreated septic group was significant (p < .05). No growth was observed from blood cultures taken 24 h after sepsis induction. All control experiments yielded negative cultures. The results of these experiments demonstrated that liposomal cefoxitin exerts an enhanced bactericidal effect in liver and lungs during Gram-negative sepsis.

Definition of the role of enterococcus in intraabdominal infection: analysis of a prospective randomized trial.

BACKGROUND: The role of enterococcus in intraabdominal infection is controversial. This study examines the contribution of enterococcus to adverse outcome in a large intraabdominal infection trial. METHODS: A randomized prospective double-blind trial was performed to compare two different antimicrobial regimens in combination with surgical or percutaneous drainage in the treatment of complicated intraabdominal infections. A total of 330 valid patients was enrolled from 22 centers in North America. RESULTS: In 330 valid patients, 71 had enterococcus isolated from the initial drainage of an intraabdominal focus of infection. This finding was associated with a significantly higher treatment failure rate than that of patients without enterococcus (28% versus 14%, p < 0.01). In addition, only Acute Physiology and Chronic Health Evaluation II score and presence of enterococcus were significant independent predictors of treatment failure when stepwise logistic regression was performed (p < 0.01 and < 0.03). Risk factors for the presence of enterococcus include age, Acute Physiology and Chronic Health Evaluation II, preinfection hospital length of stay, postoperative infections, and anatomic source of infection. There was no difference between the clinical trial treatment regimens with regard to overall failure, failure associated with enterococcus, or frequency of enterococcal isolation. CONCLUSIONS: This study is the first to report enterococcus as a predictor of treatment failure in complicated intraabdominal infections. This trial also identifies several significant risk factors for the presence of enterococcus in such infections.

Operative management of intra-abdominal infections.

Operation for intra-abdominal infection aims to prevent further contamination of the abdominal cavity, treat the underlying source of infection, and prevent residual or recurrent sepsis by cleaning the peritoneal cavity. Aggressive attempts at early diagnosis are warranted, even if laparotomy is occasionally required for diagnostic as well as therapeutic purposes. Conversely, the degree to which more aggressive methods of peritoneal debridement are helpful is the subject of great controversy that can be resolved only by prospective, randomized multicenter trials. Current standard treatment consists of closure, drainage, or excision of the source of contamination; intra-operative saline or antibiotic lavage of the peritoneal cavity; fascial closure; and secondary or delayed primary closure of the wound.

C-reactive protein levels predict postoperative septic complications.

We studied 108 patients undergoing clean-contaminated and dirty surgical procedures to determine whether daily C-reactive protein (CRP) measurements for 14 days postoperatively could predict the occurrence of septic complications prior to clinical diagnosis. Diagnostic criteria for septic complications and positive CRP response were defined in advance of the study. The CRP assays were carried out using an automated laser nephelometer system after the patient's discharge from the hospital. Forty-six septic complications were diagnosed in 40 patients. These complications consisted of wound infection (23), urinary tract infection (11), pneumonia (six), upper respiratory tract infection (three), intra-abdominal abscess (one), and other (two). The CRP testing was found to have a positive predictive value of 69% and a negative predictive value of 78%. We conclude that serial CRP measurements may be a valuable adjunct to surgical care in patients at high risk of postoperative septic complications.

Steroids, APACHE II score, and the outcome of abdominal infection.

OBJECTIVE: To compare the outcome of abdominal infection in patients with or without previous systemic glucocorticoid therapy and to determine the effect of steroid administration on the relationship between APACHE II (Acute Physiology and Chronic Health Evaluation) scores and mortality. HYPOTHESIS: Steroid therapy leads to greater mortality and relatively lower APACHE II scores. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: Two hundred ninety-seven consecutive adult patients with abdominal infection treated by surgical or percutaneous drainage. Treatment was at the clinician's discretion. Seventy-one patients received systemic steroid therapy. OUTCOME MEASURES: APACHE II score, clinical course, and death in hospital; relationship between APACHE II score and mortality in the steroid and no steroid groups. RESULTS: Thirty-three patients receiving steroid therapy (46%) died vs 55 (24%) of 226 patients not receiving steroid therapy. The APACHE II score (P < .0001) and steroid administration (P = .04) were each independently associated with death. Steroid-treated patients had the same probability of dying as "nonsteroid" patients with an APACHE II score a mean of 3.7 points higher (95% confidence limits, 0.03 and 7.7). The confidence that 2, 3, or 4 extra APACHE II points is the appropriate correction for steroid-treated patients is 80%, 60%, or 40%, respectively. CONCLUSIONS: Patients receiving steroid therapy appear to be at higher risk of dying of abdominal infection than predicted by APACHE II scores. The number of patients receiving cancer chemotherapy was too small to determine whether this was an additional risk factor. In the design of clinical trials stratified by APACHE II scores, steroid-treated patients should either be excluded or assigned two extra APACHE II points.

Pneumonia complicating abdominal sepsis. An independent risk factor for mortality.

Nosocomial pneumonia (NP) is associated with a significant mortality, 66% in a previous retrospective study of NP complicating intra-abdominal sepsis (IAS). We prospectively compared the outcome of NP complicating IAS with that of recurrent IAS (R-IAS) in the absence of NP. Data were collected prospectively on 300 patients with IAS; 34 patients who presented with pneumonia were excluded from the analysis (44% mortality). One hundred seventy-one patients with no NP and no R-IAS (group 1) had a hospital mortality of 20% (34 patients); 36 without NP in whom R-IAS developed (group 2) had a 17% mortality (six patients); and 47 with NP but no R-IAS (group 3) had a 53% mortality (25 patients). Finally, 12 patients who had both NP and R-IAS suffered a 75% mortality (nine patients). We examined the relationships among the following putative risk factors and mortality: APACHE (acute physiology and chronic health evaluation) II score (at initial presentation with IAS), the need for mechanical ventilatory assistance following initial treatment for peritonitis, steroid requirement, generalized peritonitis vs abscess, and the need for surgical as opposed to percutaneous treatment. Using mortality as the dependent variable, group 2 vs 3 as the explanatory variable, and the risk factors as confounders, logistic regression analysis indicated that the group difference was significant after controlling for confounders. We conclude that NP complicating IAS is an independent risk factor associated with a significant mortality compared with R-IAS. These data challenge the notion that death in IAS is usually due to recurrent or persistent intra-abdominal infection.

APACHE II score and abdominal sepsis. A prospective study.

Therapeutic trials for intra-abdominal sepsis require pretreatment stratification; physiologic scoring has been recently proposed for this purpose. We have prospectively tested the validity of one such scoring system, namely, the Acute Physiology and Chronic Health Evaluation (APACHE II). As part of a larger database, we correlated APACHE II scores with mortality in 100 patients hospitalized for generalized peritonitis or abdominal abscess. Use of steroids was recorded because of our suspicion that steroids increase mortality but blunt the physiologic response to sepsis. Thirty-one patients died, including 12 of 19 patients receiving steroids. Stepwise discriminant analysis revealed that the APACHE II score and steroid use were each independently associated with the rate of mortality. We report a prospective validation of pretreatment APACHE II scoring in abdominal sepsis. Steroid use is an independent risk factor.

Anergy secondary to sepsis in rats. Relation to outcome.

A rat model was developed to determine if delayed hypersensitivity skin tests during early peritonitis would predict outcome. Presensitized rats were simultaneously tested intradermally with keyhole-limpet hemocyanin and given four types of fecal bacteria and 10% barium sulfate intraperitoneally. Rats were divided into four groups according to inoculum dose. Skin tests were read at 24 hours in survivors and correlated with death and abscesses during the next 19 days. In the two groups with greatest mortality, 35% of anergic rats died, compared with 0% of reactive rats. In the three groups with most abscesses, anergic rats had more abscesses than those that reacted. Overall, 90% of anergic rats died or had abscesses v only 10% of reactors. We concluded that the outcome of untreated peritonitis is determined in the first 24 hours; anergy at that time predicts death or abscess formation.

Guidelines for clinical care: anti-infective agents for intra-abdominal infection. A Surgical Infection Society policy statement.

Several antibiotics have been marketed for therapeutic use in intra-abdominal infection. Often, these agents do not provide a sufficient spectrum activity against both facultative and obligate anaerobic gram-negative organisms, or have certain toxic effects that would not otherwise support their use. Guidelines have been developed for selection of antibiotic therapy for intra-abdominal infections and are presented as a statement of the Surgical Infection Society endorsed by the Executive Council. These guidelines are restricted to infections derived from the gastrointestinal tract and deal with those microorganisms commonly seen in such infections. The recommendations are based on in vitro activity against enteric bacteria, experience in animal models, and documented efficacy in clinical trials. Other concerns regarding pharmacokinetics, mechanisms of action, microbial resistance, and safety were also used in the formation of these guidelines. For community-acquired infections of mild to moderate severity, single-agent therapy with cefoxitin, cefotetan, or cefmetazole or ticarcillin-clavulanic acid is recommended. For more severe infections, single-agent therapy with carbapenems (imipenem/cilastatin) or combination therapy with either a third-generation cephalosporin, a monobactam (aztreonam), or an aminoglycoside plus clindamycin or metronidazole is recommended. Regimens with little or no activity against facultative gram-negative rods or anaerobic gram-negative rods are not considered acceptable.

Surgical Infection Society position on vancomycin-resistant Enterococcus.

The risk of transfer of vancomycin resistance to staphylococci is a real possibility and has been achieved in the laboratory. Prolonged colonization occurs with vancomycin-resistant Enterococcus (VRE), and many more patients are colonized than infected. The failure to identify, isolate, and adhere to infection control measures when caring for VRE-colonized patients dooms to failure any means to control its spread. Control of vancomycin use alone is unlikely to greatly affect the number of patients at risk for VRE colonization. The global spread of VRE may be impossible to stop, but infection control measures are the most important line of defense inside hospitals.

Antimicrobial prophylaxis for surgical wounds. Guidelines for clinical care.

Prophylactic administration of antibiotics can decrease postoperative morbidity, shorten hospitalization, and reduce the overall costs attributable to infections. Principles of prophylaxis include providing effective levels of antibiotics in the decisive interval, and, in most instances, limiting the course to intraoperative coverage only. Use in The National Research Council clean contaminated operations is appropriate and, in many instances, has been proven beneficial. Antibiotic prophylaxis is also indicated for clean operations, such as those involved with insertion of prosthetic devices, that are associated with low infection risk and high morbidity. Extension of antibiotic prophylaxis to other categories of clean wounds should be limited to patients with two or more risk factors established by criteria in the study of the efficacy of nosocomial infection control (SENIC) because the baseline infection rate in these patients is high enough to justify their use. Cefazolin (or cefoxitin when anaerobic coverage is necessary) remains the mainstay of prophylactic therapy. Selection of an alternate agent should be based on specific contraindications, local infection control surveillance data, and the results of clinical trials. Newer criteria for determining the risk of "site infection" (wound and intracavitary) are in evolution and may lead to modification of these recommendations over the next several years.

Soft tissue infections and the diabetic foot.

Soft tissue infections are classified as local or spreading. Spreading soft tissue infections are potentially life-threatening conditions, requiring prompt diagnosis and treatment. The information presented is based on a literature review and the authors' clinical experience. Diagnosis of soft tissue infections is aimed at determining the level of infection (skin, fascia, muscle) and whether necrosis is present. The bacteriology of these infections is varied and is of secondary importance. Treatment of skin infections that have no dead tissue is with antibiotics alone. Infections at the fascial or muscle level and those with necrosis at any level require surgical debridement and adjuvant antibiotics. The feet of diabetic patients are prone to plantar forefoot ulcers associated with tissue destruction and infection. The vast majority are caused by mechanical factors. If local immune defenses are adequate, bacterial colonization occurs without infection. Most diabetic foot ulcers will respond to relief of pressure, which may require total contact casting. Antibiotics and debridement are required in infected or deep ulcers, or when the ulcer does not respond to total contact casting.

Pharmacodynamics of antimicrobial therapy in surgery.

INTRODUCTION: "Pharmacodynamics" refers to the relationship of drug concentrations in serum or tissues to effects on biologic systems. Concepts used to describe antimicrobial pharmacodynamics include the minimal inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), and serum bactericidal titers (SBT), as well as post-antibiotic effect. METHODS: Pertinent published literature was identified through a MEDLINE search. RESULTS: Aminoglycosides have a concentration-dependent effect on bacteria killing and possess a relatively long postantibiotic effect. Given these characteristics, single-daily dosing, where the total daily dose with a traditional aminoglycoside regimen is given as one dose, may be more efficacious compared with more frequent dosing. For beta-lactam antimicrobials, bacterial killing is related to the duration of time that the free drug concentration exceeds the bacterial MIC. Beta-lactam antimicrobials have been shown to have no, or a short postantibiotic effect. Beta-lactam antimicrobials may be more effective when administered as continuous intravenous infusions. CONCLUSIONS: Pharmacodynamic variation may result from differences in drug sensitivity among individuals and the nature of the interaction between antimicrobials and microorganisms. Proper use of pharmacokinetic and pharmacodynamic principles can result in more effective and less toxic antimicrobial regimens.

Distribution of free and liposome-encapsulated cefoxitin in experimental intra-abdominal sepsis in rats.

The distributions of radiolabelled free cefoxitin (FC) and liposome-encapsulated cefoxitin (LC) were compared in an animal model of intra-abdominal sepsis. Intraperitoneally administered LC was initially retained in the peritoneal cavity with subsequent preferential drug targeting to the liver (14% injected LC) and spleen (6% injected LC) by 3 h post-injection. Differing patterns of liposomal drug and lipid retention indicated that drug release from the liposome complex occurred within the peritoneum, liver and spleen. Intraperitoneal FC was rapidly taken up into the systemic circulation, with peak recovery in the blood (9% injected FC) and liver (5% injected FC) at 1 h post-injection. FC was also rapidly eliminated; 7% of the injected drug was recovered in the kidney 1 h post-injection. A negligible amount of FC was recovered in the spleen and very little FC or LC was found in the lungs of treated animals. Unlike FC, LC was found to provide a sustained bactericidal drug level (> 40 micrograms mL-1) in the peritoneal fluid for up to 5 h post-injection. LC also achieved significantly higher drug levels, compared with FC, within the liver at 3 and 5 h post-injection. Since severe intra-abdominal sepsis is often characterized by the presence of intraphagocytic bacteria in hepatic and splenic reticuloendothelial systems, the enhanced delivery of liposome-encapsulated anti-microbial agents, such as cefoxitin, to the liver and spleen may provide a more effective treatment for the septic condition.