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Snapshots for January 2008

Louie, Ted MD

Infectious Diseases in Clinical Practice: January 2008 - Volume 16 - Issue 1 - p 6-8
doi: 10.1097/ipc.0b013e318162flad
Snapshots for January 2008
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Poster Session 174(D). What's New in Diagnostics for Infectious Diseases? No. D-1591. Improving the Quality of Mid-Stream Urine Samples With a Collection Device1

Urine cultures are most accurate in identifying true pathogens when clean-catch midstream urine samples are used. However, the incidence of contamination (as defined by the presence of epithelial cells, mixed flora, or nonpathogenic bacteria) is high. Consequently, unnecessary antibiotic courses are given for false-positive urine cultures, and more urine cultures are ordered in an effort to determine if these "infections" have cleared. The present group from Manchester, United Kingdom, used a commercially available urine collection device called the Whizz (made by JBOL Ltd, Oxford, United Kingdom) to automatically separate the early urine (more likely to contain nonpathogenic bacteria) from true midstream urine, without any interruption in urine flow.

In 3 sites, a total of 1700 females had urine samples taken: 680 supplied urine via the usual collection technique, whereas 1020 gave samples via the Whizz urinary collection device. By the author's definition, 22.5% of the conventionally supplied samples were contaminated, whereas only 4.6% of the samples taken via the Whizz device were contaminated (P < 0.001).

Thus, the Whizz device standardizes and simplifies the collecting of urine samples. The authors also reported that at 1 site, there were 63% less follow-up urine cultures taken, as there were fewer positive initial urine cultures.

Comment: The Whizz is a funnel-shaped device with 2 ends, one of which leads into a sample container. According to the manufacturer, the device "incorporates a flow-sensitive sampling channel and diverter which excludes the initial low-flow portion of the urinary stream." The high-flow midportion of the urinary stream is diverted into the sample container, whereas the low-flow initial portion of the urinary stream is diverted out the other tube. (For more information and a helpful picture, visit the company's Web site at A key question is the availability and affordability of this device, and if it will be reimbursable. I would also be interested in knowing if use of the Whizz device cuts down significantly on the use of antibiotics, thus rendering it cost effective.

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Poster Session 104K. MRSA Bacteremia: Virulence, Resistance and Impact. No. K-1096. Nephrotoxicity Associated With High Dose vs. Standard Dose Vancomycin Therapy2

Vancomycin has often been dosed to achieve a trough of 5 to 15 mg/L. More recently, some guidelines have recommended achieving higher troughs for conditions such as methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and meningitis. By going for higher trough levels, are we subjecting the patients to a higher chance of vancomycin-induced nephrotoxicity?

The authors traced back all patients in their institution who had received intravenous vancomycin for 72 hours or longer and who had at least 1 vancomycin level drawn, during calendar year 2006. Hemodialysis patients were excluded. The authors then did a retrospective chart review on these patients. They separated the patients into 2 groups, those with trough levels 5 to 15 mg/L (n = 130) and those with more than 15 mg/L (n = 88). They defined nephrotoxicity as an increase in serum creatinine of 0.5 mg/dL on 2 consecutive occasions, compared with "baseline" creatinine. They found there was a 6.2% incidence of nephrotoxicity in the group with low trough levels, as opposed to an 18.2% incidence in the group with high trough levels (P <0.01).

Comment: This is a timely study, as we face higher incidences of community-acquired MRSA, health care-associated MRSA, heteroresistance, and MIC creep. In the face of this, clinicians often have to make decisions about how aggressively they want to dose vancomycin.

Note this was a retrospective study, and the groups were not matched. As there were many potential confounding factors, it cannot be ascertained how much vancomycin was the cause of nephrotoxicity in the group with higher trough levels. Furthermore, we are not given the breakdown of diagnoses, so it is also possible that the second group may have had a higher incidence of serious deep MRSA infections such as endocarditis, meningitis, or pneumonia.

However, this study does take a much needed look at vancomycin trough levels. As the authors stated, prospective studies will be necessary to examine this subject further.

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Slide Session 42(K). Emerging Epidemiology of Clostridium difficile-Associated Disease (CDAD). No. K-603. Changing Incidence of C. difficile-Associated Diarrhea in Quebec Is Associated With Changing Strain Prevalence3

Since an outbreak of Clostridium difficile-associated disease (CDAD) in Quebec in 2003-2004,4,5 there has been mandatory surveillance of CDAD rates in local hospitals. In addition, in 2006, 45 hospitals sent in 10 consecutive C. difficile samples for typing by pulsed-field gel electrophoresis to look for proportions of strain types, including epidemic strains NAP1 and NAP2. NAP1, in particular, was felt to be highly virulent.

Results: Between 2005 and 2006, the incidence of CDAD decreased 38% to 11.1 cases/10,000 patient-days. The percentage of NAP1 strain was 57% in 2005 and 52% in 2006. The NAP2 strain decreased from 18% to 8% over the same period, and this strain actually was not detected in samples from 88% of hospitals that had a NAP2 predominance in 2005.

By using multivariate Poisson regression models, the authors noted that "for each 1% of increase in NAP1 presence, there was a 1% increase in CDAD incidence (P < 0.01)." Conversely, hospitals where the percentage of NAP1 decreased to less than 50% in 2006 had the biggest decrease in CDAD incidence. "Decreasing NAP1 predominance coupled with effective infection control measures in hospitals helped to decrease CDAD incidence."

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Poster Session 174D. What's New in Diagnostics for Infectious Diseases? No. D1599. Improved Microbiologic Diagnosis of Prosthetic Shoulder Infection (PSI) by Explanted Shoulder Prostheses Sonication Followed by Concentration and Prolonged Incubation of Anaerobic Cultures of Sonicate Fluid6

The microbiologic diagnosis of prosthetic shoulder infections (PSIs) can be difficult. Prosthetic shoulder infections are often associated with biofilm, and culturing periprosthetic tissue or joint fluid does not always yield a pathogen. Culturing material from the biofilm may be of greater help in identifying the pathogen. Furthermore, the authors have found Propionibacterium species to be important pathogens in PSI, and routine handling of cultures may not always produce a positive culture.

In previous work, the authors used sonication of explanted shoulder prostheses, and this fluid was cultured. This technique detected about 50% of PSI. In the present paper, the authors sought to increase their yield by concentrating the sonicate fluid.

Patients undergoing prosthetic shoulder revision at Mayo Clinic Rochester between December 2005 and February 2007 were studied. Prosthetic shoulder infection was defined as one or more of the following: intraoperative purulence, pathological finding consistent with acute infection, presence of sinus tract, or 2 or more periprosthetic tissue cultures positive for the same organism. These results in the same patients were compared with the authors' newer method of explanting the shoulder prostheses, sonication in Ringer solution, concentration of the fluid, and incubation, including prolonged anaerobic incubation.

Of 41 patients, 11 were diagnosed with PSI by the above criteria. Periprosthetic tissue culture was 73% sensitive, whereas the concentrated sonicate fluid cultures were 82% sensitive. Periprosthetic culture was 93% specific, whereas concentrated sonicate fluid cultures were 100% specific. Propionibacterium species were the most common bacteria detected (63% by periprosthetic tissue culture, 56% by sonicate cultures).

Comment: A recent article in New England Journal of Medicine 7 by the same group described the same technique for use in diagnosing prosthetic hip and knee infections. In this larger study, 331 patients undergoing revision of hip and knee prostheses were reviewed. Seventy-nine were defined as having infection. The sensitivity of periprosthetic tissue culture was 60.8%, whereas the sensitivity of concentrated sonicate fluid was 78.5% (P < 0.001). The specificities were similar in both groups. Also of interest, the concentrated sonicate fluid cultures were more sensitive than traditional culture techniques in cases where patients had received antibiotics in the 14 days before their joint surgery.

The technique is fairly simple, although it does require careful handling, and the use of a sterile bag large enough to sonicate the shoulder prosthesis.

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Session 54. Meet the Experts Session. Rapid Molecular Methods in the Diagnosis of Infectious Diseases8

This research group demonstrated a new technique (IBIS T5000) for identifying and characterizing bacteria. Using polymerase chain reaction (PCR) and mass spectrometry, the researchers were able to rapidly identify MRSA as well as check for mupirocin resistance, erm-mediated macrolide resistance, USA type, and the presence of Panton-Valentine leukocidin gene, with high accuracy. The T5000 has also been used to trace the origin of 2 Acinetobacter outbreaks in the US military.8-10 At present, the authors find the utility of this test to be mostly for surveillance cultures and to help identify and characterize outbreak strains.

Comment: Routine cultures are cumbersome and typically take days to identify bacteria. With the increase in resistant organisms and impending mandatory surveillance cultures for MRSA in a number of states, there has never been a greater need for more rapid techniques for identifying and characterizing MRSA, vancomycin-resistant Enterococcus,and resistant gram-negative rods such as Acinetobacter. This field is rapidly developing, and there are now various PCR-based technologies as well as fluorescence in situ hybridization techniques which can rapidly detect organisms such as vancomycin-resistant Enterococcus.11 The T5000, using both PCR and mass spectrometry, appears to be fast and accurate, as well as fairly inexpensive. In the next few years, most hospitals will have to decide on which technology to purchase for more rapid identification of bacteria, both for infection control purposes and for more precise choice of antibiotics in treating patients.

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Poster Session 27(H). HIV: ART-Associated Complications. No. H-374. Clinical Presentation of Hypersensitivity Reaction to Abacavir (ABC HSR) by HLA-B*5701 Status12

The authors conducted chart reviews to identify the possible cases of hypersensitivity reaction to abacavir (ABC HSR). Patients included had at least 2 of the following: skin rash, fever, gastrointestinal manifestations, respiratory, or constitutional symptoms, within 6 weeks of starting abacavir. Patients meeting this definition were then given abacavir skin patch testing and evaluated for the presence of HLA-B*5701. Subjects who were HLA-B*5701-positive were more likely to have more symptoms suggestive of ABC HSR, 70% tested positive by skin test, and symptoms tended to develop sooner. Subjects who were HLA-B*5701 negative had fewer symptoms suggestive of ABC HSR, 0% tested positive by skin test, and symptoms often developed later.

Comment: It is now possible to test patients before introduction of abacavir, to see if they are more likely to manifest symptoms of hypersensitivity. This does sound preferable to the traditional way of telling the patient of the possibility of fever and rash and hoping they follow up with you if this should occur.

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Poster Session 92(E). Problematic Organisms and Drug Combinations. No. E-922. In Vitro Activity of Colistin (COL) Against Multi-drug-Resistant (MDR) Acinetobacter baumannii (ACN)13

Multidrug-resistant Acinetobacter baumannii (MDR-ACN) has become a worldwide problem. Antibiotic choices are severely limited, with colistin (COL) one of the few remaining effective antibiotics. The authors investigated the in vitro killing activity of COL versus MDR-ACN. They took 48 clinical isolates from a single hospital in Thailand; 83% were positive for metallo-β-lactamase by E-strip. Colistin had a fast and sustained killing activity against MDR-ACN with MICs of less than or equal to 0.25 μg/mL. For isolates greater than 0.5 μg/mL, the killing activity was not sustained. The authors concluded that "COL may not be reliable as monotherapy against MDR-ACN with MIC less than 0.5."

Comment: With increasing use of COL, there have been reports of COL resistance and heteroresistance. Some authors have looked into the use of antibiotic combinations to treat MDR-ACN. Carbapenems and COL may have synergy against MDR-ACN.14,15

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1. Dryden MS, Gentry H, Merreday T, et al. Improving the quality of mid-stream urine samples with a collection device. Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 174(D), no. D-1591.
2. Nguyen M, Wong J, Lee C, et al. Nephrotoxicity associated with high dose vs. standard dose vancomycin therapy. Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 104K, no. K-1096.
3. Gilca R, Loo V, Hubert B, et al. Changing incidence of C. difficile-associated diarrhea in Quebec is associated with changing strain prevalence. Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20; Chicago, IL. 2007 Session 42(K), no. K-603.
4. Pepin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ. 2005;173:1037-1042.
5. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353:2442-2449.
6. Piper KE, Jacobson MJ, Cofield RH, et al. Improved microbiologic diagnosis of prosthetic shoulder infection (PSI) by explanted shoulder prostheses sonication followed by concentration and prolonged incubation of anaerobic cultures of sonicate fluid. Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 174D, No. D-1599.
7. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007;357:654-663.
8. Helfand MS, Ecker DJ, Carroll KC, et al. Rapid molecular methods in the diagnosis of infectious diseases. Presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 54.
9. Elker JA, Massire C, Hall TA, et al. Identification of Acinetobacter species and genotyping of A. baumannii by multilocus PCR and mass spectrometry. J Clin Microbiol. 2006;(44):2921-2932.
10. Hujer KM, Hujer AM, Hulten EA, et al. Analysis of antibiotic resistance genes in multidrug resistant Acinetobacter species isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob Agents Chemother. 2006;(50):4114-4123.
11. Toombs L, Weekes E, Forrest G, et al. Impact of peptide nucleic acid fluorescence in situ hybridization for enterococcal blood stream infections. Session 34, no. 131. IDSA: 2006.
12. Martorell C, Saag M, Blick G, et al. Clinical presentation of hypersensitivity reaction to abacavir (ABC HSR) by HLA-B*5701 status. Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 27(H), no. H-374.
13. Burgess DS, Carden MF, Nathisuwan S, et al. Problematic organisms and drug combinations. No. E-922. In vitro activity of colistin (COL) against multi-drug-resistant (MDR) Acinetobacter baumannii (ACN). Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 92(E), no. E-922.
14. Pankey GA, Ashcraft DS. Polymyxin B plus meropenem shows synergy against MER-resistant Acinetobacter baumannii by time-kill assay. Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 92(E), no. E-913.
15. Sopirala MM, Mangino JE, Bannerman T, et al. Antimicrobial synergy testing for multi-drug resistant Acinetobacter baumannii. Paper presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, IL. Session 92(E), no. E-914.
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