Effects of reducing beta-lactam antibiotic pressure on intestinal colonization of antibiotic-resistant gram-negative bacteria

Background: We determined the effects of two antibiotic policies (predominance of either β-lactam antibiotics or fluroquinolones) on acquisition with third-generation cephalosporin-resistant Enterobacteriaceae (CRE) and fluoroquinolone-resistant CRE (FCRE) in two ICUs, with monitoring of other variables that may influence acquisition. Methods: After an 8-month baseline period, units were randomized to a predominant β-lactam antibiotic regimen (weekly cycling of ceftriaxone, amoxicillin-clavulanic acid and fluroquinolones) or a fluoroquinolone regimen for 3 months, with cross-over for another 3 months. Acquisition of CRE and FCRE was determined by microbiological surveillance. Results: During baseline, acquisition rates for CRE and FCRE were 14/1,000 and 2/1,000 patient days at risk, respectively. Cross-transmission of CRE accounted for ≤25% of acquisitions, and CRE acquisition was associated with the use of β-lactam antibiotics (amoxicillin-clavulanic acid in particular). As compared to baseline, β-lactam antibiotic use [in defined daily dose (DDD)/1,000 patient days] was reduced from 854 to 526 (-39%) and 555 (-35%) during both intervention periods. Fluoroquinolone use was increased from 150 and 129 DDD/1,000 patient days in baseline and the β-lactam period to 514 DDD/1,000 patient days (+243%) in the fluoroquinolone period. Reductions in β-lactam use were not associated with reduced CRE acquisition [adjusted HRs were 1.0 (95% CR: 0.5-2.2) and 1.1 (95% CI: 0.5-2.5) during both periods, respectively]. Increased use of fluoroquinolones was associated with increased acquisition of FCRE [adjusted HR 4.1 (95% CI: 1.4-11.9; p < 0.01]. Infection control variables remained comparable during all periods. Conclusion: A 35-39% reduction of β-lactam exposure was not associated with reduced acquisition of CRE, whereas a 243% increase of fluoroquinolone use increased acquisition of FCRE

Increasing the frequency of hand washing by healthcare workers does not lead to commensurate reductions in staphylococcal infection in a hospital ward

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

Basal-like breast cancers: the phenotypic disparity between the cancer-initiating cells and tumor histology

Recent evidence suggests that a rare-cell population with a stem cell phenotype maintains breast tumors. Therefore, to devise breast cancer therapies that are more effective, we need to understand the unique biology of these cancer stem cells. Currently, very little is known about the origin of cancer stem cells and their relationship to the tumor phenotype. A recent study from Smalley's group demonstrates that targeting an inactivating Brca1 mutation to the luminal progenitors could yield basal-like breast cancers. This observation suggests that the inherent plasticity of the primitive cells can be hijacked by the tumorigenic processes to produce tumors with an unpredictable phenotype

Dynamics of ampicillin-resistant Enterococcus faecium clones colonizing hospitalized patients: data from a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Little is known about the dynamics of colonizing <it>Enterococcus faecium </it>clones during hospitalization, invasive infection and after discharge.</p> <p>Methods</p> <p>In a prospective observational study we compared intestinal <it>E. faecium </it>colonization in three patient cohorts: 1) Patients from the Hematology Unit at the University Hospital Basel (UHBS), Switzerland, were investigated by weekly rectal swabs (RS) during hospitalization (group 1a, n = 33) and monthly after discharge (group 1b, n = 21). 2) Patients from the Intensive Care Unit (ICU) at the University Medical Center Utrecht, the Netherlands (group 2, n = 25) were swabbed weekly. 3) Patients with invasive <it>E. faecium </it>infection at UHBS were swabbed at the time of infection (group 3, n = 22). From each RS five colonies with typical <it>E</it>. <it>faecium </it>morphology were picked. Species identification was confirmed by PCR and ampicillin-resistant <it>E. faecium </it>(ARE) isolates were typed using Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). The Simpson's Index of Diversity (SID) was calculated.</p> <p>Results</p> <p>Out of 558 ARE isolates from 354 RS, MT159 was the most prevalent clone (54%, 100%, 52% and 83% of ARE in groups 1a, 1b, 2 and 3, respectively). Among hematological inpatients 13 (40%) had ARE. During hospitalization, the SID of MLVA-typed ARE decreased from 0.745 [95%CI 0.657-0.833] in week 1 to 0.513 [95%CI 0.388-0.637] in week 3. After discharge the only detected ARE was MT159 in 3 patients. In the ICU (group 2) almost all patients (84%) were colonized with ARE. The SID increased significantly from 0.373 [95%CI 0.175-0.572] at week 1 to a maximum of 0.808 [95%CI 0.768-0.849] at week 3 due to acquisition of multiple ARE clones. All 16 patients with invasive ARE were colonized with the same MLVA clone (<it>p </it>< 0.001).</p> <p>Conclusions</p> <p>In hospitalized high-risk patients MT159 is the most frequent colonizer and cause of invasive <it>E. faecium </it>infections. During hospitalization, ASE are quickly replaced by ARE. Diversity of ARE increases on units with possible cross-transmission such as ICUs. After hospitalization ARE are lost with the exception of MT159. In invasive infections, the invasive clone is the predominant gut colonizer.</p

Rare Occurrence of Methicillin-Resistant Staphylococcus aureus CC130 with a Novel mecA Homologue in Humans in Germany

MRSA CC130 containing the mecA homologue mecALGA251 were reported from the UK and from Denmark so far from cattle and humans. Here we report on 11 MRSA CC130 among a sample of 12691 isolates of human origin collected from January 2006 until June 2011. MRSA CC130 grew insufficiently on chromogernic agar plates for detection of MRSA; the agglutination test for presence of PBP2a was negative. We designed primers for specific detection of mecALGA251 as well as for concomitant detection of both, mecLGA251 and mecA. As already described, the isolates exhibited spa-types t843, t1736, and t1773. The ccrA homologue indicated the presence SCCmecXI. When subjected to further characterization by means of a commercially available microarray the isolates were negative for sak chp, and scn, and as expected positive for hla, untruncated hlb, and hld. They furthermore contained edinB, aur, slpA, slpB, slpE. From genes coding for surface and cell wall associated products the ica-operon, cap8, clfA, clfF, ebpS, fnbA, fnbB, sdrC were detected but not cna. The isolates were negative for enterotoxin genes and tst, as well as for eta, and etb; agr-type was III

Use of multiple methods for genotyping Fusarium during an outbreak of contact lens associated fungal keratitis in Singapore

<p>Abstract</p> <p>Background</p> <p>In Singapore, an outbreak of fungal keratitis caused by members of the <it>Fusarium solani </it>species complex (FSSC) was identified in March 2005 to May 2006 involving 66 patients. Epidemiological investigations have indicated that improper contact lens wear and the use of specific contact lens solutions were risk factors.</p> <p>Methods</p> <p>We assessed the genetic diversity of the isolates using AFLP, Rep-PCR, and ERIC-PCR and compared the usefulness of these typing schemes to characterize the isolates.</p> <p>Results</p> <p>AFLP was the most discriminative typing scheme and appears to group FSSC from eye infections and from other infections differently.</p> <p>Conclusion</p> <p>There was a high genomic heterogeneity among the isolates confirming that this was not a point source outbreak.</p

The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria

Backgroud: The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address. Methods/Principal Findings: A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains. Conclusions/Significance: The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance