2:00 p.m.
J Jose, K Riederer, S Shemes, L Johnson, R Khatib. In-vitro Effect of Vancomycin Pressure on Methicillin Resistant Staphylococcus aureus Blood Isolates: Comparison of SCCmec Type II versus Type IV. St. John Hospital and Medical Center, Detroit, MI
2:15 p.m.
S. Rajaguru, G. E. Stein, C. Smith, L. Dybas, D. Havlicheck. Serum Antifungal Activity of 100 mg & 200 mg Micafungin against Candida spp. Michigan State University
2:30 p.m.
I Molano, N Gilpin , PP Shah, A Sheth, B Robinson-Dunn, C F Carpenter. Recovery of Susceptibility of Pseudomonas aeruginosa (PA) to Ciprofloxacin after a Formulary Substitution of Moxifloxacin for Levofloxacin. Beaumont Hosp, Royal Oak, MI
2:45 p.m.
C. Kosmidis, S Seo, G Kaatz. Prevalence of Efflux Pump (EP) Gene Overexpression (OE) in Clinical and Environmental S. aureus (SA) Isolates. JD Dingell VAMC and Wayne State University School of Medicine, Detroit, MI.
3:00 p.m.
J Aguilar,1,2; MA Huaman,1,3; D Baxa,1,2; A Golembieski1,2; I Brar,1,2; N Markowitz,1,2 Epidemiologic Trends and Drug Resistance Mutation Patterns among Individuals Newly Diagnosed with HIV in Detroit. Henry Ford Hospital, Detroit, MI
3:15 p.m.
E. J. McGrath1, R. Salloum2, X. Chen3, Y. Jiang3, C. Becker4, K. Boldt-MacDonald5, R. Chu6 and J. Y. Ang1. Short-dwell Ethanol-Lock Therapy in Children with Intravascular Device-Related Blood Stream Infections 1Carman and Ann Adams Department of Pediatrics, Division of Infectious Diseases, Wayne State University/Children’s Hospital of Michigan, Detroit, Michigan, United States; 2Department of Combined Internal Medicine and Pediatrics, Wayne State University/Detroit Medical Center, Detroit, Michigan, United States; 3Carman and Ann Adams Department of Pediatrics, Pediatric Prevention Research, Wayne State University, Detroit, Michigan, United States; 4Department of Pediatric Imaging, Wayne State University/Children’s Hospital of Michigan, Detroit, Michigan, United States; 5Children’s Hospital of Michigan, Detroit, Michigan, United States and 6Carman and Ann Adams Department of Pediatrics, Division of Hematology & Oncology, Wayne State University/Children’s Hospital of Michigan, Detroit, Michigan.
3:30 p.m.
T Chopra,R Severson, K Kaye, G Alangaden. Factors Predictive for Severe Clostridium difficile infection (CDI) in the Elderly–A Case-Control Study. Detroit Medical Center, Wayne State University, Detroit MI
3:45 p.m.K Rao, S Cinti. Clostridium difficile Enteritis – A series of cases in the University of Michigan Health System from 2007 – 2008. University of Michigan Health System.
In-Vitro Effect of Vancomycin Pressure on Methicillin Resistant Staphylococcus aureus Blood Isolates: Comparison of SCCmec Type II versus Type IV
Jinson Jose MD, Kathleen Riederer, Stephen Shemes, Leonard Johnson MD, Riad Khatib MD
St. John Hospital and Medical Center, Detroit, MI
Background: Methicillin resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (VA), including hetero intermediate resistance (hVISA), is reported more commonly among SCCmec type II isolates. Whether this is due to VA exposure or SCCmec type related genetic background is unknown. We studied the effects of VA in-vitro pressure in MRSA SCCmec type II and IV blood isolates. Methods: MRSA SCCmec type II and IV blood isolates with VA MIC=2µg/ml (12 each) plus USA 100 and 300 controls were grown in Brain Heart Infusion broth culture (107 CFU/ml) without and with VA challenge (2 and 3µg/ml) for 10 days (d) followed by 10d serial passage on Tryptic Soy Agar without VA (stability phase). Etest VA MIC and Etest Macromethod (MM) (VA and Teicoplanin [TP]) hVISA screening was performed at baseline and every 2d during VA challenge and stability passage. Changes in VA/TP-MM readings, VA MIC and phenotypic features were compared. Results: Growth was noted in all isolates at 2µg/ml VA without change in VA MIC. Stable TP-MM increase was noted in 3 (25%) SCCmec type IV strains at 2d challenge. At 3µg/ml VA, growth was suppressed in 1 (8.3%) SCCmec type II for 8d and 8 (66.7%) type IV for 2-9d (p=0.004; Mann-Whitney test). VA MIC increased from 2 to 4µg/ml in 1 (8.3%) type II and 3 (25%) type IV isolates. VA/TP-MM showed stable increase in 3 SCCmec type II (1 with MIC increase) and 4 SCCmec type IV isolates (3 with MIC increase). Stable increase for only TP-MM occurred in 1 and 3 SCCmec type II and IV, respectively. Time to increase was similar for SCCmec type II and SCCmec type IV (4.5 vs 4.9d). Small colony phenotype was stably induced with VA 3µg/ml pressure in 1 SCCmec type II and 2 SCCmec type IV isolates. Conclusions: Exposure to VA at 2µg/ml had no or minimal effect on 107 CFU/ml cultures of MRSA SCCmec type II and IV. At 3µg/ml VA pressure, growth was inhibited in more SCCmec type IV isolates but VA/TP-MM increases were comparable in type II and IV isolates, suggesting hVISA emergence is SCCmec type independent. Phenotypic switch to small colonies was seen rarely in both type II and IV. VA MIC rise to 4µg/ml suggests that induced resistance may go beyond hVISA to possibly VISA.
Serum Antifungal Activity of 100 mg & 200 mg Micafungin against Candida spp.
S. Rajaguru, G. E. Stein, C. Smith, L. Dybas, D. Havlicheck Michigan State University – Division of Infectious Diseases.
Micafungin (M) is fungicidal against Candida spp. in vitro but its activity can be significantly altered by serum proteins. In this study, we analyzed the antifungal activity of M in serum from non-neutropenic patients receiving 100 mg of M daily (n=8) or 200 mg of M daily (n=8) for presumptive Candida infection. The peak (end of a 1h infusion) and trough levels of M were determined by a validated HPLC assay. Antifungal activity against Candida spp., including FSK1 mutants, was analyzed via CLSI methodology and time-kill curves (geometric mean CFU/mL) were graphed. The demographics and APACHE II scores of the two patient groups were similar. Peak serum levels were 4.8 ± 1.5 mg/L and 18.4 ± 5.8 mg/L in patients receiving 100 mg and 200 mg of M, respectively. Antifungal activity (> 1 log CFU/mL) was observed by 6h against strains of C. glabrata and C. albicans, including FSK1 mutants, with MICs of ≤0.25 ug/mL . The kill curves for the two doses were similar against these isolates. No antifungal activity was observed against strains with MICs ≥ 0.5 ug/mL with either dose of M. The high protein binding of M (99%) in serum limits its antifungal activity suggesting that immune factors (not higher doses) enhance clinical efficacy.
Recovery of Susceptibility of Pseudomonas aeruginosa (PA) to Ciprofloxacin after a Formulary Substitution of Moxifloxacin for Levofloxacin.
Ilonka Molano, MD, Nick Gilpin , MD, Prakash P. Shah, PharmD, Anjly Sheth, PharmD, Barbara Robinson-Dunn, PhD, Christopher F. Carpenter, MD; Beaumont Hosp, Royal Oak, MI, USA.
Background: PA is a highly virulent pathogen and a frequent cause of nosocomial infections, including hospital-acquired pneumonia, ventilator-associated pneumonia, and complicated urinary tract infections. Its propensity to multidrug resistance, including a marked rise in resistance to antipseudomonal fluoroquinolones, has resulted in limited options to treat certain isolates. Ciprofloxacin resistance, in particular, has been associated with exposure to ciprofloxacin and levofloxacin. We describe our experience at a large teaching hospital where a recovery of PA susceptibility to ciprofloxacin was observed after a formulary substitution of moxifloxacin in place of levofloxacin.
Methods: Serial susceptibility data was retrospectively abstracted from annual and semiannual antibiograms produced from 1997 to 2008 at William Beaumont Hospital, a 1061-bed teaching facility in Royal Oak, Michigan. The susceptibility of PA to ciprofloxacin was analyzed with respect to the formulary inclusion of fluoroquinolones, including ciprofloxacin (entire study period), levofloxacin (1997 through 2002), and moxifloxacin (2003 onward).
Results: The susceptibility of PA to ciprofloxacin decreased from 75% in 1997 to a nadir of 51% in 2003. After the substitution of moxifloxacin in place of levofloxacin in 2003, a recovery of susceptibility was observed, reaching 70% in 2008. While levofloxacin was included in the formulary from 1997-2002, PA susceptibility rates to levofloxacin decreased by 4.4% per year. During the period after levofloxacin was removed from formulary (and moxifloxacin substituted in its place), the susceptibility slope increased by 3.7% per year. Utilizing an analysis of covariance, this difference achieved statistical significance (p-value < 0.0001).
Conclusions: Levofloxacin was associated with decreased susceptibility of PA to ciprofloxacin, with reversal of this decline observed after substitution for levofloxacin with moxifloxacin in the hospital formulary.
Key Words: Ciprofloxacin Resistance, Pseudomonas aeruginosa, Antimicrobial Stewardship.
Prevalence of Efflux Pump (EP) Gene Overexpression (OE) in Clinical and Environmental S. aureus (SA) Isolates. C. Kosmidis, S Seo, G Kaatz. JD Dingell VAMC and Wayne State University School of Medicine, Detroit, MI.
Background: SA possesses efflux-related resistance mechanisms for antibiotics and disinfectants. Efflux may be more prevalent in environmental isolates related to exposure to disinfectant agents. We determined the prevalence of EP gene OE in SA clinical and environmental isolates.
Materials and methods: Bloodstream isolates of SA were collected from 6 medical centers in the US and Germany. Environmental surfaces in patient care areas from 2 medical centers were sampled on selective media and SA isolates were verified by coagulase testing. mecA and qacA/B were detected by PCR. Screening for OE of chromosomal EP genes norA, norB, norC, mepA, mdeA, sepA and sdrM was performed using multiplex qRT-PCR.
Results: 55.1 and 41.7% of clinical and environmental isolates, respectively, carried the mecA gene. The prevalence of OE of EP genes for clinical and environmental isolates, respectively, was: 17.1% and 15.5% for norA, 12.8% and 8.6% for norB, 5.4% and 1.7% for mepA, 2.5% and 1.7% for norC, 0.6% and 1.7% for sdrM, and 0.2% and 0 for mdeA. No OE of sepA was detected. Significant variability in prevalence of gene OE was observed among different medical centers. norA was the most commonly overexpressed gene in 4 medical centers. qacA/B was uncommon in clinical but relatively frequent in environmental isolates (0.6 and 8.6%, respectively.
Conclusions: Efflux-mediated resistance is prevalent in SA clinical isolates from various geographical locations. The most commonly implicated gene is norA. The plasmid-based qacA/B genes were more common in environmental than in clinical SA isolates. Selective pressure by antiseptics and disinfectants used in the hospital setting may select for these isolates. SA strains colonizing environmental surfaces were more likely to lack mecA, suggesting a different origin, possibly from colonized health-care workers.
Epidemiologic Trends and Drug Resistance Mutation Patterns among Individuals Newly Diagnosed with HIV in Detroit.
Javier Aguilar, MD 1,2; Moises A Huaman, MD 1,3; Dwayne Baxa, PhD 1,2; Alicia Golembieski1,2; Indira Brar, MD 1,2; Norman Markowitz, MD1,2
ABSTRACT:
Objective: To characterize local epidemiologic trends and drug resistance mutation patterns among those with newly diagnosed HIV infection seen at Henry Ford Hospital in Detroit from 2006-2008.
Design: Retrospective study.
Methods: A retrospective analysis was conducted of medical records from individuals who were ≥18 years of age and had a new diagnosis of HIV infection between. Individuals who received care at the time of diagnosis and underwent genotypic resistance testing were included in the study.
Results: From January 2006 through December 2008,137 individuals were newly diagnosed with HIV and underwent genotypic resistance assay. Study population was predominantly male (75%) and African-American (77%). 47% had CD4 ≤200 cells/uL and were considered late presenters. Prevalence of TAR was 21% (95%CI: 14.6 - 28.8). One, two and three class mutations were present in 17%, 3% and 1% respectively. Non-nucleoside reverse transcriptase mutations occurred in 11%, nucleoside reverse transcriptase mutations in 8% and protease inhibitor mutations in 8%. Lower CD4+ count and higher HIV viral load on presentation were both associated to lesser frequency of TAR (p<0.001).
Conclusions: Late diagnosis of HIV and transmitted antiretroviral resistance are relatively common in Detroit. While most newly diagnosed persons were candidates for antiretroviral therapy on presentation, the high prevalence of TAR has potential implications in the selection of first-line HAART.
Short-dwell Ethanol-Lock Therapy in Children with Intravascular Device-Related Blood Stream Infections.
E. J. McGrath1, R. Salloum2, X. Chen3, Y. Jiang3, C. Becker4, K. Boldt-MacDonald5, R. Chu6 and J. Y. Ang1. 1Carman and Ann Adams Department of Pediatrics, Division of Infectious Diseases, Wayne State University/Children’s Hospital of Michigan, Detroit, Michigan, United States; 2Department of Combined Internal Medicine and Pediatrics, Wayne State University/Detroit Medical Center, Detroit, Michigan, United States; 3Carman and Ann Adams Department of Pediatrics, Pediatric Prevention Research, Wayne State University, Detroit, Michigan, United States; 4Department of Pediatric Imaging, Wayne State University/Children’s Hospital of Michigan, Detroit, Michigan, United States; 5Children’s Hospital of Michigan, Detroit, Michigan, United States and 6Carman and Ann Adams Department of Pediatrics, Division of Hematology & Oncology, Wayne State University/Children’s Hospital of Michigan, Detroit, Michigan, United States.
Background: Intravascular devices (IVD) are foreign materials inserted into the vasculature of patients for various purposes. IVD-related bloodstream infection (BSI) is a major complication of IVD use. Traditional IVD-related BSI management consists of removal of the infected IVD and systemic antimicrobial therapy; however salvage of infected IVD by ethanol-lock therapy (ELT) along with systemic antimicrobials may be more feasible in patients with limited vascular access.
Objective: To review our experience with the use of short-dwell ELT (70% ethanol, 4 to 25 hour dwell times for < 3 days) in combination with systemic antimicrobials for treatment of IVD-related BSI at Children’s Hospital of Michigan (CHM).
Design/Methods: A retrospective chart review was done on all patients 0 - 21 years with documented IVD-BSI who underwent ELT at CHM from 1/1/07-7/15/09. The primary outcome was sterilization of the infected IVD after ELT as defined by a negative blood culture obtained from the infected IVD < 25 hours after ELT. Secondary outcomes were: recurrence of BSI within 30 days after ELT, successful retention of IVD and safety and tolerability of ELT. Results: 68 patients ages 2 m -19 years (mean+SD: 7y+6y) with 93 episodes of IVD-BSI were included. Underlying conditions were: malignancy (20), bone marrow transplant (9), hematologic disorders (5), short bowel syndrome (8), infections requiring prolonged antimicrobial therapy (6), and others (15). 44/93 (47%) were immunosuppressed. 93 episodes of BSI occurred over 12,792 catheter-days. 48 pathogens were identified and included various Gram-positive, Gram-negative and fungal organisms. 30/93 (32%) had polymicrobial infection. Mean duration of concomitant systemic antimicrobial therapy was 8 days. ELT in addition to systemic antimicrobials eradicated IVD-BSI in 79/93 (85%) of episodes. BSI recurred within 30 days after ELT in 23/93 (25%), but only 7/23 were related to prior organisms. IVD were successfully retained in 69/93 (74%) and ELT was well tolerated.
Conclusions: This study suggests that short-dwell ELT in addition to systemic antimicrobials is safe and effective in eradicating IVD-related BSI caused by various pathogens in a diverse group of pediatric patients. ELT may have a role in the treatment of IVD-BSI avoiding the need for IVD removal in patients requiring long-term venous access. Larger prospective studies are needed.
Factors Predictive for Severe Clostridium difficile infection (CDI) in the Elderly – A Case-Control Study.
Teena Chopra M.D.,R Severson MPH ,Keith Kaye M.D., George Alangaden M.D., Detroit Medical Center, Wayne State University, Detroit MI
Background:
Advanced age is a risk factor for severe CDI. However, the factors that predict severe CDI in the elderly are undefined. We performed a case-control study of severe CDI in older adults, to determine clinical and laboratory features that predict progression to severe disease.
Methods:
A case-control study was performed of older adults (age≥60 years) with severe CDI, hospitalized at 2 acute- care hospitals at the Detroit Medical Center, between January 2005 to December 2008. All patients with diarrhea and a positive Clostridium difficile toxin assay result on stool specimen were identified from the laboratory database. Case patients were ≥60 years of age and had severe CDI defined as: CDI resulting in admission to an intensive care unit, or colectomy, or death <30 days after onset of CDI. Control group were patients age ≥60 years with non-severe CDI. Patient demographics, co-morbidities and clinical and laboratory features were analyzed.Univariate logistic regression was applied to identify predictors of severe CDI.
Results:
The incidence of severe CDI was 13% over a 4 year study period. Of the 37 cases with severe CDI, 2 underwent colectomy,36 were admitted to ICU for CDI and 27 died from complications related to CDI. Median duration from symptom onset to development of severe CDI was 5.5-days. The median maximum white cell count during CDI was 24 k/cumm for the cases and 17.4 k/cumm for the controls. On univariate analysis, risk factors associated with severe CDI included:use of diuretics (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.24,6.36 and low serum albumin(<2.5g/dl) (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.38,7.23. Univariate logistic regression identified the following characteristics at initial presentation to be predictive of severe CDI: presence of abdominal distension (Odds ratio(OR)= 8.22,95% CI =3.47,19.52) and presence of a rapidly fatal condition at admission(OR=3.6,95% CI=1.35,7.87).
Conclusions: Abdominal distension and presence of a rapidly fatal condition at initial presentation are significant predictors of progression to severe CDI in hospitalized older adults.
Clostridium difficile Enteritis – A series of cases in the University of Michigan Health System from 2007 – 2008.
Authors: Krishna Rao, MD; Sandro Cinti, MD.
Institution: University of Michigan Health System.
Abstract:
Clostridium difficile (C. diff) is an organism that causes many illnesses grouped together as C. difficile associated disease (CDAD), which is of increasing importance now as one of the leading nosocomial infections, with epidemic rates in some health centers and hospitals. The rates of inpatient infection had risen at the University of Michigan from 2007 – 2008, doubling in the 1st quarter of 2008 when compared to the 1st quarter of 2007, and the costs to patients and the healthcare system as a whole increased. C diff typically affects the large bowel in a patient with prior or ongoing antibiotic exposure. However, there are documented case reports in the literature of CDAD in patients s/p total colectomy, a group once believed to be at low risk for this infection. This newly recognized disease is being termed C. difficile enteritis. Although we know about how C. difficile colitis affects the large bowel, there is little research about infection in colectomized patients, with only a few case reports in the current literature and evidence that metaplasia of the small bowel to colonic mucosa is involved.
We reviewed C. difficile enteritis in patients s/p total colectomy during our time of increased prevalence of nosocomial CDAD (2007 – 2008) within the University of Michigan Health System to better characterize the prevalence of this rare infection within our institution, and also to try to identify risk factors. We searched our institutional EMR using a research-oriented search engine within the charts of 3000+ patients with positive C. diff toxin testing from 2007 – 2008. This revealed a total of 8 patients s/p any type of colectomy (both total and subtotal) getting CDAD afterwards. Five of these patients had total colectomies, and 3 of those patients had a colectomy because of CDAD, but were included in the series because of continued disease post-operatively. All of them had some form of immunosuppresssion and prior antibiotic use. 4 patients were on TPN, 4 had no enteral feeds (TPN or IV fluids only), all had prior episodes of CDAD, and those that expired did so from CDAD.
Conclusion: Although the prevalence of CDAD in patients s/p colectomy at our institution was low during a period where CDAD in general was high at our institution, the cases we had came with serious morbidity and mortality. Common features shared by the patients included immunosuppression, poor nutrition, and antibiotic exposure.
Kim, Kiup A. et al. “Clostridium difficile Small-Bowel Enteritis After Total Proctocolectomy: A Rare But Fatal, Easily Missed Diagnosis. Report of a Case.” Diseases of the Colon and Rectum. 2006; 50: 920–923.