effect of prolonging clostridium difficile (cd) treatment on recurrence rate in patients receiving...
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Effect of prolonging Clostridium difficile (CD) treatment on recurrence rate in patients receiving concomitant systemic antibiotic therapy
• 5-yr retrospective single-centre study in 301 patients with first
episode of Clostridium difficile infection (CDI) (period 2007-2011)
• Bivariate analysis of 65 patients with concomitant systemic antibiotic
therapy* and follow-up of ≥12 wk:
– 23 patients with standard CD treatment duration (35%)
– 42 patients with prolonged CD treatment duration (defined as ≥15 days; 65%)
• Highest CDI recurrence rate in patients receiving oral vancomycin:
– 36% for vancomycin alone
– 50% for vancomycin and metronidazole
– 20% for metronidazole alone
Ponce-Terashima R. IDSA 2012 abs.293
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Effect of prolonging Clostridium difficile (CD) treatment on recurrence rate in patients receiving concomitant systemic antibiotic therapy
Prolonging CD treatment in patients on concomitant antibiotics may not reduce the CDI recurrence rate
Ponce-Terashima R. IDSA 2012 abs.293
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Colonoscopic vs nasogastric faecal transplantation for treatment of Clostridium difficile infection (CDI)
• Pooled analysis of study data (published until December 2011) on faecal transplantation for recurrent CDI
• 12 studies with 182 patients
Postigo R. IDSA 2012 abs.315
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Colonoscopic vs nasogastric faecal transplantation for treatment of Clostridium difficile infection (CDI)
• No significant AEs were noted
Faecal transplantation for recurrent CDI via colonoscopy or nasogastric tube appears highly and equally effective, and safe
Postigo R. IDSA 2012 abs.315
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Impact of probiotics on occurrence of Clostridium difficile infection (CDI) in patients receiving high-risk antibiotics
• Retrospective cohort study in adult inpatients who received antibiotics (with high risk of acquiring CDI) during ≥5 days in the period July-Dec 2010– Selected high-risk antibiotics: clindamycin, ceftriaxone, ciprofloxacin, levofloxacin– Patient demographics, comorbidities, probiotics use (Lactobacillus GG and
Saccharomyces boulardii), concomitant proton pump inhibitor (PPI) use
• 20 of 389 (5.1%) had CDI within 90 days of antibiotic use:
Dickson J. IDSA 2012 abs.299
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Impact of probiotics on occurrence of Clostridium difficile infection (CDI) in patients receiving high-risk antibiotics
• 65% of patients who developed CDI used levofloxacin but even after adjusting for levofloxacin use, risk remains 2.6-fold higher for probiotics users compared with non-users (P<0.05)
• Effect of concomitant PPI use on occurrence of CDI:
The use of probiotics seems to increase the risk of CDI in patients on high-risk antibiotics; concomitant PPI use may even
further increase this risk
Dickson J. IDSA 2012 abs.299
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Differential risk of antibiotics on community-associated Clostridium difficile infection (CDI)
• Meta-analysis of 4 observational studies comparing antibiotic vs non-antibiotic use in non-hospitalised patients (retrieved from 465 publications from 2 databases by 2 independent reviewers)
In the community setting, there seems to be substantial variation between different antibiotic classes for the risk of CDI
Brown K. IDSA 2012 abs.723
Risk factors associated with systemic absorption of oral vancomycin in the treatment of Clostridium difficile colitis (CDC)
• Retrospective single-centre study in 85 adult (≥18 yr) patients with CDC receiving oral vancomycin during ≥5 days without concomitant iv vancomycin
• Vancomycin serum levels during therapy assessed on day 5, 10 and weekly thereafter
• Multivariate logistic regression analysis to assess risk factors for systemic absorption of vancomycin with P value of ≤0.20 on Chi-square analysis
Carver PL. IDSA 2012 abs.1637
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Risk factors associated with systemic absorption of oral vancomycin in the treatment of Clostridium difficile colitis (CDC)
• 60 patients (71%) had ≥1 detectable vancomycin plasma level (range 0.05-9.94 µg/ml) of which 15 patients ≥1 level >2.5 µg/ml
CDC severity, oral vancomycin dose, ICU admission and gastrointestinal pathology seem risk factors for systemic absorption
Carver PL. IDSA 2012 abs.1637
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Outcome of intestinal microbiota transplantation on death/colectomy in patients with severe/fulminant Clostridium difficile infection (CDI)
• Single-centre retrospective study (period May 2010-Dec 2011) in 28 patients with severe/fulminant colitis due to CDI (median age 60 yr) unresponsive to conventional CDI therapy
• Donors for intestinal microbiota transplantation: screened for negative serology for HIV, hepatitis A/B/C and syphilis, stool tested by PCR for negative C. difficile DNA
• Outcome: – Primary: clinical improvement (resolution of diarrhoea)– Secondary: CDI recurrence within 100 days
Hassan M. IDSA 2012 abs.1224
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Outcome of intestinal microbiota transplantation on death/colectomy in patients with severe/fulminant Clostridium difficile infection (CDI)
• 28/28 (100%) tolerated the procedure well, no AEs
• 28/28 (100%) recovered dramatically within 1-4 days post transplant
• 28/28 (100%) had no recurrence within 100 days post transplant
Intestinal microbiota transplantation for refractory severe/fulminant colitis due to CDI appears life-saving and safe
Hassan M. IDSA 2012 abs.1224
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Removal of catheter and therapy duration in cancer patients with Staphylococcus aureus central line-associated bloodstream infection (BSI)
• Single-centre, retrospective study in cancer patients with suspected Staphylococcus aureus central line-associated BSI (SA-CLBSI; period 2005-2011)
• Of 762 patients, 299 patients (304 episodes) fulfilled the CDC definition of SA-CLBSI
• Patient characteristics*:– 52% with haematological malignancy– 23% with neutropenia– 69% had fever– 76% had sepsis– 28% had signs of inflammation at the catheter site– 64% developed complications
El Zakhem A. IDSA 2012 abs.897
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Removal of catheter and therapy duration in cancer patients with Staphylococcus aureus central line-associated bloodstream infection (BSI)
• Staphylococcus aureus isolates*:– 51% had MIC of 2 to vancomycin– 47% were methicillin resistant (MRSA)
• Catheter: – 64% removed/exchanged within 3 days (80% within 7 days)
– Removal within 3 days associated with lower relapse compared with no/late removal after 7 days (P=0.009)
• BSI episodes:– 109/304 (36%) was uncomplicated at time of presentation– 29/109 (27%) became late complications– No association between therapy duration (14 days as cut-off) and late
complications, relapse/recurrence, all-cause mortality in uncomplicated group
Catheter removal within 3 days of SA-CLABSI onset seems associated with a lower relapse rate in cancer patiens; for uncomplicated
infections, therapy duration beyond 14 days may not be necessary
El Zakhem A. IDSA 2012 abs.897
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Comparison of nasal mupirocin ointment with povidone-iodine solution for preventing Staphylococcus aureus (SA) surgical site infection (SSI)
• Investigator-driven, open-label randomised trial: 1 application nasal povidone-iodine (PI) solution vs 5-days nasal mupirocin ointment prior to surgery on SA SSI outcome in patients after arthroplasty or spine fusion surgery
• Standard in both groups: 2 applications of topical chlorhexidine gluconate (CHG)
• Endpoints:– Primary: deep SA SSI at 3-mo follow-up (CDC/NHSN case definition, determined by
blinded investigators)– Secondary: superficial SA SSI, deep SSI due to any pathogen, drug-related AEs,
risk factors for infection assessed by uni/multivariate analysis
• Preoperative SA colonisation associated with deep SA SSI (P=0.002)• ITT analysis:
– 1 vs 0 superficial SA SSI for PI vs mupirocin group– 6/887 (0.68%) vs 14/879 (1.59%) deep SSI due to any pathogen for PI vs mupirocin
group (P=0.07)
Phillips MS. IDSA 2012 late breaking abs.3
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Comparison of nasal mupirocin ointment with povidone-iodine solution for preventing Staphylococcus aureus (SA) surgical site infection (SSI)
• AE due to study drug or CHG: 3% for PI group vs 10% for mupirocin group (P<0.001)
Given the lower rate of deep SSI due to SA, PI could be an effective and safe preoperative alternative to mupirocin
Phillips MS. IDSA 2012 late breaking abs.3
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Penicillin-susceptible Staphylococcus aureus (SA) infection in an era of multidrug resistance
• Retrospective chart review of patients with SA in blood cultures in
lab database (period July-Dec 2011): adults only, no repeat episodes
• Study background :
– 5% of methicillin-sensitive SA isolates are sensitive to penicillin
– Aimed to characterise frequency of serious infections due to penicillin-sensitive
SA (PSSA) and how these patients are managed
• Of 445 patients with SA: 280 had MSSA
• Of 280 patients with MSSA: 58 (21%) had PSSA
• Mortality in PSSA group during index hospitalisation: 14%
• 2 excluded (no adults), 8 received broad spectrum antibiotics or
died 48 patients with PSSA were analysed for treatment choice
Goodman J. IDSA 2012 abs.169
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Penicillin-susceptible Staphylococcus aureus (SA) infection in an era of multidrug resistance
Labs should (continue to) report penicillin sensitivity for SA infection because large part of MSSA is PSSA;
many patients with PSSA receive inappropriate therapy
Goodman J. IDSA 2012 abs.169
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Clinical outcome of linezolid vs vancomycin treatment in patients with ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA)
• Multi-centre, retrospective observational IMPACT-HAP study in
144 ICU patients with VAP due to MRSA treated with linezolid vs
vancomycin in the US
• VAP due to MRSA defined according to CDC/NHSN surveillance
and if MRSA isolated from tracheal aspirate or bronchoalveolar
lavage
• Exclusion: patients with do-not-resuscitate or do-not-intubate order
• Clinical success defined as symptom improvement or resolution by
day 14 or at earlier hospital discharge
Peyrani P. IDSA 2012 abs.1283
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Clinical outcome of linezolid vs vancomycin treatment in patients with ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA)
• Propensity-adjusted logistic regression model: lowering clinical success rate with increasing APACHE II score for both treatment groups but significantly higher rates at each APACHE II score for linezolid compared with vancomycin (P<0.001)
Patients with VAP due to MRSA treated with linezolid seem more likely to respond favourably compared with patients
treated with vancomycin
Peyrani P. IDSA 2012 abs.1283
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Prevalence and risk factors of carriers of extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae
• Prospective single-centre study in 525 patients admitted to hospital
(over 1 week) and screened for ESBL
• Excluding paediatric and obstetric departments, rectal swabs
collected
• 56/525 (10.6%) were positive for ESBL:
– 41/56 (73.2%) with E. Coli
– 76.8% without positive clinical cultures or not previously known as ESBL carrier
• Multivariate analysis to identify independent risk factors for ESBL
carriage
Shitrit P. IDSA 2012 abs.1438
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Prevalence and risk factors of carriers of extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae
• Of screened patients with ≥1 risk factor (N=273), 49 (18%) was positive compared with 7/252 (3%) of screened patients without risk factors
• Screening of population at risk would discover 88% of positive pts
11% prevalence of ESBL carriers among new hospital admissions and the identification of risk factors warrant targeted screening
Shitrit P. IDSA 2012 abs.1438
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Role of procalcitonin (PCT) in guiding antibiotic therapy
• Descriptive review of RCTs using PCT to guide antibiotic therapy
– 2 RCTs in outpatient primary care setting:
• About 1,000 patients with upper/lower respiratory tract infections
• Antibiotic use: PCT cut-off value of 0.25 µg/l was used
– 5 RCTs in emergency room and inpatient medical floor setting:
• Patients with COPD exacerbation, bronchitis and community-acquired
pneumonia
• Antibiotic use: control group according to standard of care vs PCT group
according to algorithm (start if PCT level >0.25 µg/l,
stop if PCT level <0.25 µg/l)
– Several RCTs in ICU setting:
• Antibiotic use: started in control and PCT group but stopped according to
PCT-based algorithm
Maskey M. IDSA 2012 abs.761
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Role of procalcitonin (PCT) in guiding antibiotic therapy
• Significant reduction in antibiotic use
– In outpatient setting
– In PCT-guided group compared with control group in
emergency/inpatient setting
• Shorter duration of antibiotic treatment in ICU setting in PCT vs
control group
• Similar clinical outcome in PCT group compared with control group
• No adverse clinical outcome in PCT group in neither of studies
PCT seems a promising biomarker for bacterial infection and may give guidance in antibiotic therapy
Maskey M. IDSA 2012 abs.761
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Antibiotic combination therapy vs monotherapy for Pseudomonas aeruginosa bloodstream infections
• 2-centre retrospective review of adult patients with bloodstream infections due to Pseudomonas aeruginosa (period 2006-2011) who started on antibiotic combination therapy
• Comparison between patients who continued to those who changed to monotherapy after report of antimicrobial susceptibility testing (AST)
• Of 239 patients, 148 (62%) started on combination therapy, and after AST:
Viehman JA. IDSA 2012 abs.762
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Antibiotic combination therapy vs monotherapy for Pseudomonas aeruginosa bloodstream infection
• No difference between groups in age, gender, presence of diabetes, neutropenia, septic shock, history of organ transplant mechanical ventilation, Charlson comorbidity index, rate of C. difficile colitis (±10%) and acute renal failure after antibiotics (±17%)
• Multivariable logistic regression analysis: no difference for adjusted in-hospital mortality between combi and monotherapy (39% vs 32%, P=0.19)
Continuing double coverage in pts with Pseudomonas bloodstream infection once AST data are available seems not beneficial
Viehman JA. IDSA 2012 abs.762
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Efficacy and safety of moxifloxacin in patients with secondary peritonitis
• Post-hoc pooled analysis of 4 prospective multi-centre phase III RCTs in adult patients with complicated abdominal infections: – Secondary peritonitis with APACHE score of 7.0±5.0 and community-
acquired origin
– Moxifloxacin 400 mg iv/PO or iv od vs comparators:• ertapenem (1.0 g iv od)
• piperacillin/tazobactam (3.0 g/0.375 g iv qid)
• ceftriaxone 2.0 g od iv/metronidazole (500 mg iv bid or tid)
• amoxicillin/clavulanic acid (800 mg/114 mg PO bid or 500 mg/125 mg PO tid)
• Primary efficacy endpoint: clinical success* at the test-of-cure visit at 11-45 days after the end of therapy in PP population
De Waele J. IDSA 2012 abs.784
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Efficacy and safety of moxifloxacin in patients with secondary peritonitis
• Overall clinical success rate: similar between groups for different infection sites
• Safety analysis:
Compared with other antibiotics, moxifloxacin appears to be an effective and safe option for the treatment of secondary peritonitis
De Waele J. IDSA 2012 abs.784
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Clinical and economical outcomes of meropenem and piperacillin-tazobactam treatment using extended compared with intermittent infusions in critically ill patients
• Single-centre retrospective chart review of patients – Receiving ≥48h meropenem (500 mg Q6h) or piperacillin-tazobactam
(PT; 3.375 g Q8h)
– Both treatments using intermittent infusions (period Jan-Dec 2010) and extended* infusions (period Nov 2011-April 2012)
• Outcomes:– Primary: in-hospital all-cause mortality
– Secondary: length of hospital stay, length of ICU stay, time to normalisation of white blood cell count and temperature
• Baseline characteristics:– Between meropenem groups (N=100): difference in continuous renal
replacement therapy and solid organ transplant
– Between PT groups (N=148): no difference
Ternes L. IDSA 2012 abs.786
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• Extended infusion in PT group: 13.2% reduction in average cost/patient/day
Clinical and economical outcomes of meropenem and piperacillin-tazobactam treatment using extended compared with intermittent infusions in critically ill patients
Extended compared with intermittent infusion seems to result in faster progression to death (significant for meropenem and likely for PT)
Ternes L. IDSA 2012 abs.786
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Impact of gentamicin-collagen sponge on the risk of surgical site infection (SSI)
• Meta-analysis of 14 publications/13 study populations on prophylactic use of gentamicin-collagen sponges for SSI:
– Cardiac surgery (N=4) - Colorectal surgery (N=5)– Gastrointestinal surgery (N=2) - Hernia surgery (N=2)
• Retrieved from PubMed/Cinahl database (period 1980-2012): data extraction independently by 2 persons, summary estimates using random-effects model
The use of gentamicin-collagen sponges appears associated with a reduced risk of SSI following cardiac (but not colorectal) procedures
Formanek M. IDSA 2012 abs.1294
Evaluation of serotonin toxicity associated with linezolid or vancomycin treatment
• Observational matched cohort study in 502 hospitalised patients treated with linezolid or vancomycin (1:1) at the Upstate New York Veterans’ Affairs Healthcare Network (period 2005-2008)
• Matching for:– Hospital– Hospital ward (ICU vs non-ICU)– Hospital length of stay prior to treatment start with linezolid/vancomycin– Age (<50, 51-75, >75 yr)– Baseline platelets (< or >100,000 cells/mm3)
• Toxicity evaluation using intensive natural word search algorithm:– Symptoms consistent with serotonin toxicity– Hunter serotonin toxicity criteria (HSTC)
Lodise T. IDSA 2012 abs.1318
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Evaluation of serotonin toxicity associated with linezolid or vancomycin treatment
• Baseline patient characteristics similar for linezolid and vancomycin groups
Low rates of serotonin toxicity are found in hospitalised patients treated with linezolid (slightly more with vancomycin)
Lodise T. IDSA 2012 abs.1318
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Treatment duration and outcomes for male urinary tract infection (UTI)
• Retrospective review of 33,336 patients with index UTI from
Veterans Affairs database (fiscal yr 2009)
• Association between patient/treatment characteristics and outcome
(UTI recurrence and Clostridium difficile infection (CDI) over 12 mo)
for index cases in uni/multivariate analysis
• Antibiotics with highest use:
– Ciprofloxacin 62.7%
– Trimethoprim/sulfamethoxazole 26.8%
Drekonja DM. IDSA 2012 abs.1322
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Treatment duration and outcomes for male urinary tract infection (UTI)
• CDI risk was higher with longer than shorter treatment duration: 0.5% vs 0.3%, P=0.02; OR 1.40; 95% CI 0.96-2.06
Longer antibiotic treatment duration of ≥7 days may be associated with increased late recurrence of UTI and subsequent CDI
Drekonja DM. IDSA 2012 abs.1322
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Relevance of empiric antibiotics for urinary tract infection (UTI) in non-critically ill patients
• Retrospective review of 447 non-critically ill patients with UTI (period June 2010-2011)
• Exclusion: requirement of ICU or inotropes, concurrent other infections
• Grouping according to susceptibility of urine cultures to empiric antibiotics used: comparison for clinical response to antibiotics at day 3-5, in-hospital mortality, length of stay
Lee SY. IDSA 2012 abs.1370
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Relevance of empirical antibiotics for urinary tract infection (UTI) in non-critically ill patients
Since no adverse clinical outcomes are found, choice of antibiotics in non-critically ill patients could be deferred to after culturing results
Lee SY. IDSA 2012 abs.1370
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Mortality outcomes and associated risk factors of Stenotrophomonas maltophilia bloodstream infections (BSI)
• Retrospective single-centre study of 116 patiens with Stenotrophomonas maltophilia BSI (period 2011-2011)
• Exclusion: patients with polymicrobial blood cultures• Patient characteristics:
– 89% received previous antibiotics– 91% had central venous catheter– 44% were in ICU– 55% had comorbid malignancy– 79% was line-related, 17% secondary, 4% undetermined– Of isolates tested (N=73): 90% sensitive to sulfamethoxazole-trimethoprim
(SMX-TMP) and 16% to ticarcillin/clavulanate– 65% were treated with appropriate antibiotics (88% of these with SMX-TMP)– Alternative regimens were ticarcillin/clavulanate (N=5), tigecycline (N=13),
moxifloxacin (N=2)
Hunter AS. IDSA 2012 abs.1706
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Mortality outcomes and associated risk factors of Stenotrophomonas maltophilia bloodstream infections (BSI)
• All-cause 14-day mortality outcome: overall 18%– Similar between patients treated with SMX-TMP and alternatives– Survivors: trend towards longer median time before appropriate therapy– 30% when treated with tigecycline (N=13) and 0% when treated with moxifloxacin
(N=2); 29% when having SMX-TMP-resistant isolates
All-cause 14-day mortality seems comparable between SMX-TMP and alternative regimens in the treatment of S. Maltophilia BSI;
independent risk factors could be dissociated
Hunter AS. IDSA 2012 abs.1706
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Dilated fundoscopic examination (DFE) for ocular candidiasis and echocardiography for infective endocarditis (IE) in patients with Candida bloodstream infection (BSI)
• Retrospective review of lab surveillance data from active residents in metropolitan Atlanta and Baltimore city and county (period March 2008-May 2010)
• For adults (≥20 yr) and children with Candida positive blood culture: review of screening DFE and echocardiography documentation (≤14 days after positive blood culture), demographic and clinical data
Doshi SS. IDSA 2012 abs.128;Doshi SS. IDSA 2012 abs. 699
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Dilated fundoscopic examination (DFE) for ocular candidiasis and echocardiography for infective endocarditis (IE) in patients with Candida bloodstream infection (BSI)
• Adults with ocular candidiasis (N=8; 5 albicans, 2 glabrata, 1 tropicalis): median age 54 yr, 5 black, 4 male, 6 with >1 positive Candida blood culture day, all required ICU admission
Doshi SS. IDSA 2012 abs.128;Doshi SS. IDSA 2012 abs. 699
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Dilated fundoscopic examination (DFE) for ocular candidiasis and echocardiography for infective endocarditis (IE) in patients with Candida bloodstream infection (BSI)
• Adults with IE (N=30; 11 with albicans): median age 63 yr, 18 had prior antibacterials, 3 had non-healthcare-associated onset of Candida BSI, 7 died ≤30 days after initial positive blood culture, 13 (43%) had >1 positive Candida culture day
• Children with IE (N=4; 3 with albicans): <60 days old, birth weight <1 kg, <28 weeks gestational age; 3 died ≤30 days after initial positive blood culture, all with >1 positive Candida culture day
Although ocular candidiasis and IE may occur, few patients with Candida BSI are screened with DFE and echocardiography
Doshi SS. IDSA 2012 abs.128;Doshi SS. IDSA 2012 abs. 699
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Liver safety of posaconazole in early salvage therapy for invasive fungal infection (IFI) caused by molds and yeasts
• Prospective multi-centre cohort phase II study with posaconazole treatment (oral 400 mg bid) in 40 patients with IFI who failed or were intolerant to prior antifungal treatment (Canada, period 2008-2011)
• Patient characteristics:– 53% had ≥1 elevated liver enzyme at entry– Conditions: leukemia (33%) > stem cell transplant (30%) > lung and renal
transplant (23%) > others (15%)– Prior therapies: voriconazole (53%) > amphotericin B (23%) > fluconazole (13%)
> caspofungin (5%)
• Efficacy analysis (according to EORTC criteria)
Haider S. IDSA 2012 abs.223
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Liver safety of posaconazole in early salvage therapy for invasive fungal infections caused by molds and yeasts
• Safety
Given its favourable efficacy/safety profile, posaconazole may be used in immunocompromised pts refractory or intolerant to other
antifungals
Haider S. IDSA 2012 abs.223
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Voriconazole therapeutic drug monitoring in haematologic and ICU patients with invasive aspergillosis (IA)
• HPLC study of 81 voriconazole plasma concentrations (VPC) in 18 patients:
– 13 ICU patients; 5 haematologic patients– 8 with probable IA, 8 with possible IA, 2 with voriconazole prophylaxis
• With target range on 1.5-5.5 mg/l:
Hoenigl M. IDSA 2012 abs.233
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Voriconazole therapeutic drug monitoring in haematologic and ICU patients with invasive aspergillosis (IA)
• Continuously low VPC in 3 patients (despite dosage increase to
12 mg/kg) discontinuation of voriconazole change to
alternative therapy: 2 on oral posaconazole, 1 on liposomal
amphotericin B
• Toxicity: 3 patients with cholestatic hepatopathy
– VPC 6.0 mg/l
– VPC 4.2 mg/l
– VPC 1.4 mg/l despite voriconazole 12 mg/kg
Given that VPCs below target range are frequently found in haematologic and ICU patients, therapeutic drug monitoring of
voriconazole may be useful
Hoenigl M. IDSA 2012 abs.233
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Longitudinal analysis of leukocyte differentials in peripheral blood of patients with acute influenza infection
• Retrospective study of experimental human challenge tests with
influenza A/Wisconsin/67/2005 (H3N2) to assess temporal
development and time-dependent utility of leukocyte differential
• Of 17 inoculated volunteers, 9 (53%) developed symptomatic
infection
• Peripheral blood: daily measurement of differentials from
immediately prior to inoculation to resolution of disease
McClain M. IDSA 2012 abs.93
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Longitudinal analysis of leukocyte differentials in peripheral blood of patients with acute influenza infection
• Lymphocyte:monocyte ratio of <2 at the time of maximal symptoms correctly classified 100% of the volunteers according to symptom status
Despite usefulness of leukocyte differentials to determine infected status, its utility is heavily time dependent
McClain M. IDSA 2012 abs.93
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Emergence of oseltamivir resistance in patients with influenza A infections
• Global observational trial IRIS: Influenza Resistance Information Study (NCT00884117)
• Patients with influenza-like illness and/or positive rapid test for influenza:
– Throat/nose swabs on day 1, 3, 6, 10 for real-time RT-PCR analysis of influenza type/subtype, resistance to neuraminidase inhibitor oseltamivir
– Severity scoring (0-3) of 7 symptoms for day 1-12
• Of 1,855 RT-PCR positives with single influenza infection in first 3 yr: 1,310 patients had influenza A
• 700/1,310 (53%) received oseltamivir monotherapy within 2 days after symptom onset: N=9 with seasonal H1, N=222 with H3N2, N=469 with H1N1 2009
Schutten M. IDSA 2012 abs.94
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Emergence of oseltamivir resistance in patients with influenza A infections
• Post day 1 emergent resistance to oseltamivir in influenza A patients: 19 out of 700 patients (2.7%):
Emergent resistance of influenza A to oseltamivir seems to occur mostly in 1-5 yr old children, without effect on symptom resolution
Schutten M. IDSA 2012 abs.94
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Use of sonication for diagnosis of orthopaedic hardware infection
• Single-centre retrospective cohort study (period 2009-2011) of 48 adult patients with removal of infected orthopaedic hardware (plates, screws, nails, K wires; no prosthetic joints)
• Measurement of agreement (kappa statistics) between results of bacterial culture of tissue with culture of sonicate fluids from orthopaedic hardware
• Sonicate fluid was incubated on blood, McConkey and chocolate agar, broth media and inoculated into aerobic and anaerobic blood culture bottles
• Patient demographics: median age 55 yr, 30 (63%) male, 8 (17%) diabetic, 12 (25%) on antibiotics 14 days prior to culture
Khumri S. IDSA 2012 abs.873
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Use of sonication for diagnosis of orthopaedic hardware infection
Sonication fluid culturing appears complimentary to tissue culturing for the diagnosis of orthopaedic hardware-associated infection but
requires optimisation
Khumri S. IDSA 2012 abs.873
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Application of whole genome sequencing (WGS) in understanding the role of patients in nosocomial transmission of Staphylococcus aureus (SA)
• Prospective single-centre study in 1,093 patients admitted to ICU
(period 2010-2011) to assess acquisition* of SA and patient-to-
patient transmission#
• Weekly serial swabs: isolates were spa-typed and underwent WGS
to assess relatedness by comparing single nucleotide variants
(SNVs)
• 15.6% of screened patients had SA (4.2% methicillin-resistant SA)
• 39/676 patients (5.8%) with >1 swab acquired SA
Price J. IDSA 2012 abs.428
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Application of whole genome sequencing (WGS) in understanding the role of patients in nosocomial transmission of Staphylococcus aureus (SA)
• 4/39 patients had patient-to-patient transmission
– 3 of 4 appeared MRSA spa type t032 outbreak-related BUT
– 2 of 4: true transmissions according to WGS (>40 SNVs)
• 10/35 acquisitions:
– No epidemiological or spa type evidence for transmission BUT
– WGS revealed clusters of highly related isolates (15-38 SNVs)
suggesting pre-ICU transmission events
In this study, minority of apparent SA acquisitions in ICU seem to be attributable to direct patient-to-patient transmission
Price J. IDSA 2012 abs.428
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Aetiology of community-acquired pneumonia in hospitalised adults in the US
• CDC EPIC (Etiology of Pneumonia in the Community) study: prospective multi-centre design enrolling US patients with community-acquired pneumonia*
• Blood: culturing and lytA/spy Streptococcus PCR• Sputum: culture and Legionella PCR• Urine: Pneumococcus and Legionella antigen testing• Naso/oropharyngeal swabs: PCR for respiratory viruses/atypical
bacteria• Preliminary data from Jan 2010-July 2011: 1,608 patients with
community-acquired pneumonia – Admission to ICU / mortality: 21% / 3% – 1st culture / PCR before inpatient antibiotics: 81% / 59%
Jain S. IDSA 2012 abs.676
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Aetiology of community-acquired pneumonia in hospitalised adults in the US
• Viral or bacterial pathogen detected in 26% and 11% respectively
Viruses seem more commonly detected than other pathogens in adults with community-acquired pneumonia
Jain S. IDSA 2012 abs.676
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Utility of pneumococcal urinary antigen test (UAT) for antibiotic therapy or stewardship
• Retrospective single-centre study in 642 inpatients with pneumococcal UAT performed (period Aug 2011-March 2012)
• 38 patients (5.9%) were positive for pneumococcal UAT• Indications (N=38):
– 58% with community-acquired pneumonia (N=22; CAP)– 29% with healthcare-acquired pneumonia (N=11; HCAP)– 13% other (N=5)– 84% had an indication for pneumococcal UAT
• De-escalation of antibiotic therapy could have occurred in 9 patients– 6 also had positive blood/sputum culture for Pneumococcus as basis for
de-escalation, resulting in role for UAT in only 3 of 642 patients (0.5%)– 1/3rd of CAP patients were de-escalated (N=7)
Because UAT seems to have little effect on antibiotic therapy course and is expensive, the utility of pneumococcal UAT is questionnable
Radigan E. IDSA 2012 abs.733
Feedback intervention on infectious disease (ID) physicians in antibiotic stewardship programme
• Prospective single-centre study in 8 ID physicians• Restricted antibiotic prescriptions:
– Daptomycin, carbapenem, linezolid, micafungin, tigecycline, voriconazole, posaconazole
– Reviewed by an ID Pharm D– Intervention: feedback on weekly ratio to individual ID physician in relation to
anonymous colleagues
• Decreased in number of restricted prescriptions for each ID physician
Feedback intervention seems to influence ID physicians’ prescribing habits and may reduce variability
Landon E. IDSA 2012 abs.741