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Hand hygiene is generally considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, several researchers have found the law of diminishing returns to apply to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance, and others have demonstrated that poor cohorting of nursing staff profoundly influences the effectiveness of hand hygiene measures. Collectively, these findings raise intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI. In order to investigate these issues further, we constructed a deterministic Ross-Macdonald model and applied it to a hypothetical general medical ward. In this model the transmission of staphylococcal infection was assumed to occur after contact with the transiently colonized hands of HCWs, who, in turn, acquire contamination only by touching colonized patients. The aim of the study was to evaluate the impact of imperfect hand cleansing on the transmission of staphylococcal infection and to identify, whether there is a limit, above which further hand hygiene compliance is unlikely to be of benefit. The model demonstrated that if transmission is solely via the hands of HCWs, it should, under most circumstances, be possible to prevent outbreaks of staphylococcal infection from occurring at a hand cleansing frequencies <50%, even with imperfect hand hygiene. The analysis also indicated that the relationship between hand cleansing efficacy and frequency is not linear - as efficacy decreases, so the hand cleansing frequency required to ensure R0<1 increases disproportionately. Although our study confirmed hand hygiene to be an effective control measure, it demonstrated that the law of diminishing returns applies, with the greatest benefit derived from the first 20% or so of compliance. Indeed, our analysis suggests that there is little benefit to be accrued from very high levels of hand cleansing and that in most situations compliance >40% should be enough to prevent outbreaks of staphylococcal infection occurring, if transmission is solely via the hands of HCWs. Furthermore we identified a non-linear relationship between hand cleansing efficacy and frequency, suggesting that it is important to maximise the efficacy of the hand cleansing process.

Source: Masters Abstracts International, Volume: 47-01, page: 0341. Adviser: Luis Ostrosky. Includes bibliographical references.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

BACKGROUND: The risk factors, microbial etiology, differentiation, and clinical features of purulent and non-purulent cellulitis are not well defined in Taiwan. METHODS: We conducted a retrospective cohort study of hospitalized adults with cellulitis in Taiwan in 2013. The demographic characteristics, underlying diseases, clinical manifestations, laboratory and microbiological findings, treatments, and outcomes were compared for patients with purulent and non-purulent cellulitis. RESULTS: Of the 465 patients, 369 had non-purulent cellulitis and 96 had purulent cellulitis. The non-purulent group was significantly older (p = 0.001) and was more likely to have lower limb involvement (p < 0.001), tinea pedis (p = 0.003), stasis dermatitis (p = 0.025), a higher Charlson comorbidity score (p = 0.03), and recurrence at 6 months post-infection (p = 0.001) than the purulent group. The purulent group was more likely to have a wound (p < 0.001) and a longer hospital stay (p = 0.001) and duration of antimicrobial therapy (p = 0.003) than the non-purulent group. The etiological agent was identified in 35.5 % of the non-purulent cases, with β-hemolytic streptococci the most frequent cause (70.2 %). The etiological agent was identified in 83.3 % of the purulent cases, with Staphylococcus aureus the predominant pathogen (60 %): 50 % of these were methicillin-resistant S. aureus (MRSA). In multivariable analysis, purulent group (odds ratio (OR), 5.188; 95 % confidence interval (CI), 1.995-13.493; p = 0.001) was a positive predictor of MRSA. The prescribed antimicrobial agents were significantly different between the purulent and non-purulent groups, with penicillin the most frequently used antimicrobial agent in the non-purulent group (35.2 %), and oxacillin the most frequent in the purulent group (39.6 %). The appropriate antimicrobial agent was more frequently prescribed in the non-purulent group than in the purulent group (83.2 % vs. 53.8 %, p < 0.001). CONCLUSIONS: The epidemiology, clinical features, and microbiology of purulent and non-purulent cellulitis were significantly different in hospitalized Taiwanese adults. Purulence was a positive predictor of MRSA as the causal agent of cellulitis. These findings provide added support for the adoption of the IDSA guidelines for empirical antimicrobial therapy of cellulitis in Taiwan.

Small stable protein domains are attractive scaffolds for engineering affinity proteins due to their high tolerance to mutagenesis without loosing structural integrity. The albuminbinding domain is a 5 kDa three-helix bundle derived from the bacterial receptor Protein G with low-nanomolar affinity to albumin. In this thesis, the albumin-binding domain is explored as a scaffold for engineering novel affinity proteins with the possible benefit of combining a prolonged serum half-life with specific targeting in a single small scaffold protein. Previously, a library was created by randomizing surface-exposed residues in order to engineer affinity to a new target antigen in addition to the inherent albumin affinity. Here, phage display selections were separately performed against the tumor antigens ERBB2 and ERBB3. The ERBB3 selection resulted in a panel of candidates that were found to have varying affinities to ERBB3 in the nanomolar range, while still retaining a high affinity to albumin. Further characterization concluded that the clones also competed for binding to ERBB3 with the natural activating ligand Heregulin. The selections against ERBB2 resulted in sub-nanomolar affinities to ERBB2 where the binding site was found to overlap with the antibody Trastuzumab. The binding sites on ABD to albumin and either target were found in both selections to be mutually exclusive, as increased concentrations of albumin reduced the level of binding to ERBB2 or ERBB3. An affinity-matured ERBB2 binder, denoted ADAPT6, which lacked affinity to albumin was evaluated as a radionuclide-labeled imaging tracer for diagnosing ERBB2-positive tumors. Biodistribution studies in mice showed a high renal uptake consistent with affinity proteins in the same size range and the injected ADAPT quickly localized to the implanted tumor. High contrast images could be generated and ERBB2-expressing tissue could be distinguished from normal tissue with high contrast, demonstrating the feasibility of the scaffold for use as diagnostic tool. In a fourth study, affinity maturation strategies using staphylococcal cell-surface display were evaluated by comparing two replicate selections and varying the stringency. A sub-nanomolar target concentration was concluded to be inappropriate for equilibrium selection as the resulting output was highly variable between replicates. In contrast, equilibrium sorting at higher concentrations followed by kinetic-focused off-rate selection resulted in high output overlap between attempts and a clear correlation between affinity and enrichment. / <p>QC 20160510</p>

Early function of a temperature-sensitive mutant of staphylophage 44A HJD was examined during the twenty-five-minute period following infection. Host cell and phage DNA were labeled with C and3H respectively. DNA was separated into linear and covalently closed circular (CCC) forms by density-gradient centrifugation. The host, S. aureus, shows no CCC DNA, and apparently carries no plasmid. Following infection with wild type phage, CCC DNA forms occur in tritiated and 1 C DNA fractions 10 to 15 min after infection. Infection with mutant at permissive temperature also demonstrates CCC DNA with both labels. Infection with mutant at nonpermissive temperature produced no CCC DNA during the first 25 min after infection. The impaired function in this mutant may be a linker protein.