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Strategies for minimizing the impact of blood culture contaminants
Clinical Microbiology Newsletter Vol. 24, No. 7
April 1, 2002
Strategies for Minimizing the Impact of Blood Culture Contaminants Sandra S. Richter, M.D., University of Iowa College of Medicine, Iowa City, IA Abstract Contaminated blood cultures are common occurrences and represent a major problem for clinical microbiology laboratories and health care institutions. These contaminated blood cultures may result in the administration of unnecessary antibiotics, prolonged hospital stays, and significant increases in hospital costs. Some of the major issues associated with blood culture contamination are reviewed, and recommendations are provided for lowering these contamination rates. Strategies have also been developed whereby the clinical and financial impact of blood culture contamination can be minimized. Introduction Contaminated blood cultures are common, accounting for more than 40% of positive blood cultures in some analyses (1,2). Bates et al. (3) reported an independent correlation of contaminated blood cultures with 20% higher laboratory charges and 39% higher antibiotic charges. Little et al. (4) found the mean hospital costs of patients with contaminated blood cultures to be $4,100 higher than those with negative blood cultures. Clinical microbiology laboratories can help limit this misappropriation of health care dollars by identifying probable contaminants, avoiding the performance of additional tests on those isolates, monitoring the institutional contamination rate, and developing strategies to prevent contamination by optimizing collection techniques. Source o f C o n t a m i n a t i o n The primary organisms responsible for blood culture contamination are skin Mailing address: Sandra S. Richter, M.D., Medical Microbiology Division, Department of Pathology, C606 GH, University of Iowa College of Medicine, Iowa City, 11452242. Tel.."319-356-2990, Fax: 319-356-4916. E-mail." [email protected]&t Clinical Microbiology Newsletter 24:7.2002
flora organisms (coagulase-negative staphylococci [CNS], Corynebacterium spp., Propionibacterium acnes, Bacillus spp., Micrococcus spp., and viridans streptococci) associated with inadequate skin antisepsis. The venipuncture site should be initially cleansed with 70% isopropyl or ethyl alcohol, followed by application of 2% iodine tincture rather than an iodophor (povidone-iodine). Iodophors are inferior because they require longer contact time for an adequate antiseptic effect. King and Price (5) demonstrated that a 2-min exposure to an iodophor was required to achieve the same reduction in skin flora attained with a 35 sec exposure to 1% iodine tincture. This has been illustrated by two studies that reported significantly higher rates of blood culture contamination with iodophors in comparison to iodine tincture (4,6). Because of concern that contamination is more likely to occur in cultures collected from intravascular devices, venipuncture is considered the preferred method for collecting blood for culture (7,8). Bryant and Strand (9) found a statistically significant higher rate of contamination among cultures collected through intravascular devices when compared to paired venipuncture ~(32002 Elsevier Science Inc.
samples. Tonnesen et al. (10) and Felices et al. (11) reported that the growth of a skin flora organism (representing a probable contaminant) occurs more often in catheter-drawn specimens, but their rates were lower (7 of 174 and 4 of 92, respectively) than those reported by Bryant and Strand (23 of 130). One possible explanation for the difference in contamination rates could be the methods of catheter disinfection employed. Tonnesen et al. (10) disinfected both the peripheral venipuncture sites and catheters in the same manner (povidone-iodine scrub, then 70% isopropyl alcohol), whereas Bryant and Strand (9) disinfected skin with 2% tincture o f iodine but only used 70% isopropyl alcohol or povidone-iodine to disinfect the catheters: The catheter disinfection method used by Felices et al.
In This Issue Strategies for Minimizing the Impact of Blood Culture Contaminants . . . . . . . . . . . . . . . . .
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Human Infection Caused by Moniliella suaveolens
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is unclear (11). Souvenir et al. (12) applied the same antisepsis (70% isopropyl alcohol followed by 10% povidone-iodine or 0.2% chlorine peroxide) to catheters and venipuncture sites and found no significant difference in contamination rates for cultures collected from intravascular devices (12 of 594) versus venipuncture (46 of 2,682). In a comprehensive study that included 55 1 paired blood cultures collected from oncology patients, DesJardin et al. (13) found a slightly lower positive predictive value (PPV) for blood cultures drawn through catheters than for those from peripheral venipuncture (63 versus 73%) but the sensitivity for true bacteremia was higher for catheterdrawn specimens (89 versus 78%). The catheter disinfection method of DesJardin et al. was identical to that of Bryant and Strand (9). In two of the studies (9,1 I), the initial aliquots of blood drawn from catheters were discarded (3 ml from arterial catheters; 5 to 10 ml from venous catheters), but there are no published data supporting this practice. When blood is drawn for culture from an intravascular catheter, a second culture should be collected by peripheral venipuncture (7). Specifically instructing personnel to apply the same procedures delineated for skin antisepsis to catheter disinfection will minimize the isolation of contaminants from cultures obtained though intravascular devices.
Identification of Contaminants The identity of an organism isolated from a blood culture can provide useful information for determining the clinical significance of a positive blood culture. The recovery of Corynebacterium spp., rl acnes, or Bacillus spp. rarely signilied a true bloodstream infection in the analysis by Weinstein et al. of 1,585 positive blood cultures (1). A higher
proportion of viridans streptococci (38% of isolates) and CNS (12% of isolates) represented definite pathogens. The number of positive blood culture sets can also be used to interpret the significance of a positive blood culture. In two separate reports, Weinstein et al. (1,14) demonstrated that 75 to 100% of blood cultures collected from patients with true bacteremia are usually positive, while contaminants often grow in only one positive blood culture among several obtained. Although the number of positive bottles within a blood culture set has been suggested to be predictive of clinical significance, a recent publication demonstrated this is not useful information for distinguishing true infection from contamination with CNS (15). Determining the clinical significance of a blpod culture isolate is a subjective process without a “gold standard”; however, some clinical indicators occur significantly more often among patients with true bacteremia than those with contaminants. These include a leukocyte count of 220,OOOJpl or <4,OOO/ul, absolute neutropenia, hypotension, hypothermia (<36“(Z), and marked fever (>4O”C) (1). The optimal approach to interpreting the significance of a positive blood culture is a critical assessment of the patient’s clinical and microbiologic data by an infectious disease physician (16). This option is not available to most microbiology laboratories when deciding whether antimicrobial susceptibility testing (AST) should be done or how to determine the institution’s blood culture contamination rate.
Laboratory-Based Algorithms A generally accepted quality assurance goal is to keep the rate of blood culture contaminants below 3% of all blood cultures drawn. Unfortunately, discrete guidelines for identifying contaminants are scarce. In 1985, Archer
(17) suggested that clinical microbiology laboratories should report CNS isolates that were likely contaminants accordingly and not perform susceptibility tests unless requested by the patient’s physician. The following scenarios were delineated as “highly suggestive” of contamination with CNS: (i) one positive culture followed by negative cultures, (ii) one culture positive out of two cultures that were drawn simultaneously, (iii) two cultures growing CNS but separated by a time interval with more than one negative culture, and (iv) only one bottle positive out of an aerobic/anaerobic two bottle set (17). The last scenario can no longer be considered suggestive of contamination (15). Trevino and Mahon (18) acknowledge the difficulty in distinguishing pathogens from contaminants and suggest that “microbiologists cannot make this determination (true pathogen or contaminant) in the laboratory; physician input and patient history are needed.” They caution readers about considering any organism isolated from two or more blood culture bottles as a contaminant. As noted above, the number of positive bottles is not a reliable criterion for determining true pathogens (15). Forbes et al. (19) note the increasing difficulty associated with interpreting the clinical significance of blood cultures yielding skin flora organisms. They present the following laboratorybased criteria to assist in recognizing probable contaminants: (i) CNS, fl acnes, Corynebacterium spp., or Bacillus spp. isolated from “one of several cultures”; (ii) growth of more than one organism from “one of several cultures”; and (iii) an organism isolated from a blood culture that is different from “the organism causing the infection at a primary site of infection.” An obvious question is how close in time can the cultures with no growth be to the posi-
NOTE: No responsibility is assumed by the Publisher for any injury an&or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods. products, instructions or ideas contained in the material herein. No suggested test or procedure should be canied out unless. in the reader’s judgment. its risk is .justitied. Because of rapid advances in the medical sciences, we recommend that the independent verification of diagnoses and drug doses should be made. Discussions, views and recommendations as to medical procedures. choice of drugs and drug dosages are the responsibility of the authors. Cliuicnl Microbiology Newsletter (ISSN 0196-4399) is issued twice monthly in one indexed volume per year by Elsevier Science Inc., 655 Avenue of the Americas, New York. NY 10010. Subscription price per year: Personal: EUR 47 for customers in Europe; $6,300 for Japan; and US$S3 for all countries other than Europe and Japan. Institutional: EUR 306 for customers in Europe: WO.600 for Japan; and US$342 for all countries other than Europe and Japan. Periodical postage paid at New York. NY and at additional mailing offices. Posbnaster: Send address changes to C‘li,ricol Micmbrologv Newsletter; Elsevier Science Inc., 655 Avenue of the Ameticas. New York, NY 10010. For customer service, phone (212) 633-395@ TOLL-FREE for customers in the United States and Canada: I-88%4ES-INFO (I 888-437-4636) or fax: (2 12) 633-3860.
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Clinical Microbiology
Newsletter 24:7.2002
Potential contaminant (coagulase-negative staphylococci, Corynebacterium spp., Propionibacterium acnes, Bad/us spp., Micrococcus spp., viridans streptococci) isolated from blood culture
Additional blood culture sets collected from the patient within 48 h show no growth
No other blood culture sets collected from the patient within 48 hr of the culture yielding a possible contaminant
Additional blood culture sets collected from the patient within 48 h positive with same organism I
L
group? I
Refer isolate to pathology resident to determine clinical significance
Report isolate as “probable contaminant” and do not perform susceptibility testing unless requested by patients physician
I
Classify isolate as a pathogen and perform susceptibility testing
Perform susceptibility testing
Figure I. Algorithm implemented at the Universily of Iowa to minimize the workup of blood culture contaminants
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tive culture to still be considered part of the series. Some laboratories subscribe to the College of American Pathologists Q-Tracks program. Laboratories participating in Q-Tracks consider a blood culture contaminated if CNS, Colynebucterium spp., fl acnes, Bacillus spp., Micrococcus spp., or viridans (alphahemolytic) streptococci are isolated from “only one of a series of blood culture specimens” (20). The length of time between cultures considered part of a series is 124 h. Autopsy cultures and specimens obtained through indwelling vascular lines are excluded. This omission of catheter-drawn cultures could result in an underestimation of an institution’s contamination rate. At the University of Iowa, we recently developed and implemented an algorithm not only to identify blood culture contaminants but also to report them to clinicians as “probable contaminants.” By not performing AST on these isolates, more than $20,000 in annual microbiology charges have been deferred. Perhaps of greater importance, the report of “probable contaminant” instead of an AST may discourage unnecessary antimicrobial agent use. The reporting of AST results for contaminants likely promotes unnecessary antimicrobial use (typically vancomycin), resulting in increased pressure for the emergence of antimicrobial resistance and higher pharmacy expenditures. The algorithm implemented at the University of Iowa is used when a skin flora organism is isolated from a blood culture and is based on the proportion of blood culture sets that are positive (Fig. 1). The algorithm considers each blood culture set (an aerobic and anaerobic bottle inoculated with blood obtained from a single venipuncture or catheter) as a single entity. If one or more additional blood cultures were obtained within *48 h and all are negative at that point in time, the isolate is considered a contaminant. If no additional blood cultures were submitted, or there were additional blood cultures collected within ~48 h yielding the same organism, a pathology resident gathers relevant clinical data from the institution’s electronic information system and makes a judgment regarding the isolate’s significance (contaminant, indeterminate, or pathogen). The resi-
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dents are instructed to determine the clinical significance of selected blood culture isolates by considering a patient’s clinical history, leukocyte count, body temperature, number of positive blood cultures, culture results from other sites, radiographic data, histopathologic findings, and current status. A copy of the article by Weinstein et al. (1) was given to each pathology resident when the algorithm was implemented and microbiology laboratory faculty are available for consultation as needed. Physicians caring for patients are often contacted by pathology residents to discuss the clinical significance of isolates, especially prior to classifying an isolate as a contaminant. AST is performed only on isolates classified as indeterminate or pathogens. Isolates of viridans streptococci are automatically considered pathogens when additional positive blood cultures yield the same organism. Occasionally, physicians request AST to be performed on isolates initially classified as contaminants. In the initial 8 months of algorithm use, this occurred with 9% of isolates that were automatically considered contaminants because of additional negative blood cultures. Because of opposition to the algorithm by neonatologists, all isolates of CNS from neonates are considered significant. To evaluate the accuracy of the algorithm-based assignments during the first 8 months the algorithm was in use, an independent retrospective chart review was performed. The algorithm was found to be acceptably accurate, with an overall PPV for identifying blood culture contaminants of 9 1.7%; the details of the algorithm evaluation are reported elsewhere (2 1,22). An added benefit to implementation of the algorithm in our laboratory was the opportunity to increase the involvement of pathology residents in clinical microbiology activities. The algorithm has become a useful tool to educate residents regarding the interpretation of positive blood cultures. Clinical microbiology laboratories without pathology residents available could use other individuals familiar with the issues of blood culture contamination to determine the clinical significance of selected blood culture isolates. Usually no more than 20 min are required to determine an isolate’s significance, and on average,
0 2002 Elsevier Science Inc.
only four isolates per week require investigation. Alternatively, a laboratory could consider all organisms isolated from additional positive blood cultures significant and investigate only isolates from patients with a single blood culture set submitted. It has been suggested that collection of only one blood culture set should be highly discouraged, not only because distinguishing contamination from septicemia is difficult, but because a single blood culture lacks sufficient sensitivity for detecting a bloodstream infection (7).
Conclusion Each microbiology laboratory should develop its own criteria for identifying contaminants within its institution. Consultation with infectious disease physicians when determining guidelines is essential. As guidelines are put into use, it is important to remain flexible and attempt to respond to questions and/or opposition by customizing the algorithm to meet individual patient and clinician needs. Once a reliable method for determining blood culture contaminants is in place, intervention can be targeted to units or individuals with elevated contamination rates. References 1. Weinstein, M.P. et al. 1997. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin. Infect. Dis. 24584-602. 2. MacGregor, R.R. and H.N. Beaty. 1972. Evaluation of positive blood cultures: guidelines for early differentiation of
contaminated from valid positive cultures. Arch. Intern. Med. 130:84-87. 3. Bates, D.W., L. Goldman, and T.H. Lee. I99 1. Contaminant blood cultures and resource utilization: the true consequences of false-positive results. JAMA 265:365-369.
Little, J.R. et al. 1999. A randomized trial of povidone-iodine compared with iodine tincture for venipuncture site disinfection: effects on rates of blood culture contamination. Am. J. Med. 107:119-125. King, T.C. and PB. Price. 1963. An evaluation of iodophors as skin antiseptics. Surg. Gynecol. Obstet. 116:361-365. Strand, C.L.. R.R. Wajsbort, and K. Sturmann. 1993. Effect of iodophor
Clinical Microbiology Newsletter24:7.2002
vs. iodine tincture skin preparation on blood culture contamination rate. JAMA 269: 1004-I 006. Weinstein, M.P. 1996. Current blood culture methods and systems: clinical concepts, technology. and interpretation of results. Clin. Infect. Dis. 23:40-46. Aronson, M.D. and D.H. Bor. 1987. Blood cultures. Ann. intern. Med. IO6:246-253. Bryant, J.K. and CL. Strand. 1987. Reliability of blood cultures collected from intravascular catheter versus venipuncture. Am J. Clin. Pathol. 88: 113-l 16.
positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients. J. Clin. M icrobiol. 36: l923- 1926. 13. DesJardin, J.A. et al. 1999. Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer. Ann. Intern. Med. 13 I:64 I-647. 14. Weinstein, M.P. et al. 1983. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev. Infect. Dis. 535-53.
IO. Tonnesen. A.. M. Peuler, and W.R. Lockwood. 1976. Cultures of blood drawn by catheters vs. venipuncture. JAMA 235: 1877.
IS. Mirrett, S. et al. 2001. Relevance of the number of positive bottles in determining clinical significance of coagulasenegative staphylococci in blood cultures. J. Clin. Microbial. 39:3279-3281.
I I. Felices, F.J. et al. 1979. Use of the central venous pressure catheter to obtain blood cultures. Crit. Care Med. 7:78-79.
16. Siegman-Igra, Y. and C. Ernst. 2000. Nosocomial bloodstream infections: are positive blood cultures misleading? Clin. Infect. Dis. 30:986.
12. Souvenir, D. et al. 1998. Blood cultures
17 Archer, G.L. 1985. Coagulase-negative
staphylococci in blood cultures: the clinician’s dilemma. Infect. Cont. 6:477-478. 18. Trevino, S. and CR. Mahon. 2000. Bacteremia, p. 1007. In C.R. Mahon and G. Manuselis (ed.), Textbook of diagnostic microbiology, 2nd ed. W.B. Saunders Company, Philadelphia. 19. Forbes, B.A. et al. 1998. Bloodstream infections, p.300. In B.A. Forbes, D.F. Sahm, and A.S. Weissfeld (ed.), Bailey & Scott’s diagnostic microbiology, 10th ed. Mosby, St. Louis. 20. College of American Pathologists. 2002. Laboratory Improvement Q-Tracks. wwwcap.ovg l/3/2002. 21. Richter, S.S. et al. Abstr. IO1st Gen. Meet. Am. Sot. Microbial., abstr. C65, p. 162,200l. 22. Richter, S.S. et al. Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm. (Submitted for publication.)
Case Report
Human Infection Caused by Monilt’ella suaveolens Shiwaji Pawar, M.D. Dennis Murray, M.D. Michigan State Universi@ East Lansing, MI
Walid Rhalife, Ph.D. Sparrow Hospital, Lansing. MI
Barbara Robinson-Dunn,
Ph.D.
William Beaumont Hospital Royal Oak, MI
Michael McGinnis,
Ph.D.
University of Te,sas Medical Branch at Galveston Galveston, TX
Opportunistic infections caused by uncommonly identified hmgi are increasingly recognized in humans and animals. Phaeohyphomycosis is a mycologic definition of growth of dematiaceous (dark-pigmented) fungi in tissue as hyphae, pseudohyphae, address: Dennis Murray, M.D., Pediatric Infectious Disease, Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48073-6769
Mailing
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2417.2002
conidia, yeast cells, or any combination of these forms. Phaeohyphomycosis can be cutaneous, subcutaneous, or systemic. Systemic infections are least common. We report what we believe is the first human case of systemic phaeohyphomycosis caused by Moniliella suaveolens.
Case Report An 18-day-old Caucasian male infant was seen in the emergency department of a large community hospital with complaints of irritability and being inconsolable. An incarcerated right inguinal hernia was diagnosed. The hernia was manually reduced, and the infant was admitted to the hospital for further management, including elective surgery. The infant had been born at 37 weeks gestation to a 30-year-old G4P2 mother. The mother was healthy during the antenatal period, except that she was treated for bacterial vaginosis with metronidazole 3 weeks prior to delivery. There was no prolonged rupture of membranes. After birth, the baby
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became increasingly tachypneic and developed grunting respirations. He was transferred to the neonatal intensive care unit. where he was started on oxygen, cefotaxime, and ampicillin. A complete blood count (CBC), C-reactive protein (CRP), and blood culture were non-contributory. A chest X ray showed diffuse interstitial pneumonia with small bilateral pleural efYi.tsions. The infant was discharged to home after 72 h with an indwelling intravenous catheter to complete 10 days of parenteral cefotaxime and ampicillin therapy for presumed bacterial pneumonia. Following discharge, the baby was seen by his primary care physician, and a mass on the right side of his neck was found. This mass was later clinically diagnosed as a cystic hygroma. The infant underwent a bilateral inguinal hemiorrhaphy and excision of the cystic hygroma after hospital admission from the emergency department. The cystic hygroma was found to extend into the superior mediastinum. Surgery was reportedly well tolerated.
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April 1, 2002
Strategies for Minimizing the Impact of Blood Culture Contaminants Sandra S. Richter, M.D., University of Iowa College of Medicine, Iowa City, IA Abstract Contaminated blood cultures are common occurrences and represent a major problem for clinical microbiology laboratories and health care institutions. These contaminated blood cultures may result in the administration of unnecessary antibiotics, prolonged hospital stays, and significant increases in hospital costs. Some of the major issues associated with blood culture contamination are reviewed, and recommendations are provided for lowering these contamination rates. Strategies have also been developed whereby the clinical and financial impact of blood culture contamination can be minimized. Introduction Contaminated blood cultures are common, accounting for more than 40% of positive blood cultures in some analyses (1,2). Bates et al. (3) reported an independent correlation of contaminated blood cultures with 20% higher laboratory charges and 39% higher antibiotic charges. Little et al. (4) found the mean hospital costs of patients with contaminated blood cultures to be $4,100 higher than those with negative blood cultures. Clinical microbiology laboratories can help limit this misappropriation of health care dollars by identifying probable contaminants, avoiding the performance of additional tests on those isolates, monitoring the institutional contamination rate, and developing strategies to prevent contamination by optimizing collection techniques. Source o f C o n t a m i n a t i o n The primary organisms responsible for blood culture contamination are skin Mailing address: Sandra S. Richter, M.D., Medical Microbiology Division, Department of Pathology, C606 GH, University of Iowa College of Medicine, Iowa City, 11452242. Tel.."319-356-2990, Fax: 319-356-4916. E-mail." [email protected]&t Clinical Microbiology Newsletter 24:7.2002
flora organisms (coagulase-negative staphylococci [CNS], Corynebacterium spp., Propionibacterium acnes, Bacillus spp., Micrococcus spp., and viridans streptococci) associated with inadequate skin antisepsis. The venipuncture site should be initially cleansed with 70% isopropyl or ethyl alcohol, followed by application of 2% iodine tincture rather than an iodophor (povidone-iodine). Iodophors are inferior because they require longer contact time for an adequate antiseptic effect. King and Price (5) demonstrated that a 2-min exposure to an iodophor was required to achieve the same reduction in skin flora attained with a 35 sec exposure to 1% iodine tincture. This has been illustrated by two studies that reported significantly higher rates of blood culture contamination with iodophors in comparison to iodine tincture (4,6). Because of concern that contamination is more likely to occur in cultures collected from intravascular devices, venipuncture is considered the preferred method for collecting blood for culture (7,8). Bryant and Strand (9) found a statistically significant higher rate of contamination among cultures collected through intravascular devices when compared to paired venipuncture ~(32002 Elsevier Science Inc.
samples. Tonnesen et al. (10) and Felices et al. (11) reported that the growth of a skin flora organism (representing a probable contaminant) occurs more often in catheter-drawn specimens, but their rates were lower (7 of 174 and 4 of 92, respectively) than those reported by Bryant and Strand (23 of 130). One possible explanation for the difference in contamination rates could be the methods of catheter disinfection employed. Tonnesen et al. (10) disinfected both the peripheral venipuncture sites and catheters in the same manner (povidone-iodine scrub, then 70% isopropyl alcohol), whereas Bryant and Strand (9) disinfected skin with 2% tincture o f iodine but only used 70% isopropyl alcohol or povidone-iodine to disinfect the catheters: The catheter disinfection method used by Felices et al.
In This Issue Strategies for Minimizing the Impact of Blood Culture Contaminants . . . . . . . . . . . . . . . . .
49
Human Infection Caused by Moniliella suaveolens
...........
53
A Case Report 0196-4399,'00 (see frontmatter)
49
is unclear (11). Souvenir et al. (12) applied the same antisepsis (70% isopropyl alcohol followed by 10% povidone-iodine or 0.2% chlorine peroxide) to catheters and venipuncture sites and found no significant difference in contamination rates for cultures collected from intravascular devices (12 of 594) versus venipuncture (46 of 2,682). In a comprehensive study that included 55 1 paired blood cultures collected from oncology patients, DesJardin et al. (13) found a slightly lower positive predictive value (PPV) for blood cultures drawn through catheters than for those from peripheral venipuncture (63 versus 73%) but the sensitivity for true bacteremia was higher for catheterdrawn specimens (89 versus 78%). The catheter disinfection method of DesJardin et al. was identical to that of Bryant and Strand (9). In two of the studies (9,1 I), the initial aliquots of blood drawn from catheters were discarded (3 ml from arterial catheters; 5 to 10 ml from venous catheters), but there are no published data supporting this practice. When blood is drawn for culture from an intravascular catheter, a second culture should be collected by peripheral venipuncture (7). Specifically instructing personnel to apply the same procedures delineated for skin antisepsis to catheter disinfection will minimize the isolation of contaminants from cultures obtained though intravascular devices.
Identification of Contaminants The identity of an organism isolated from a blood culture can provide useful information for determining the clinical significance of a positive blood culture. The recovery of Corynebacterium spp., rl acnes, or Bacillus spp. rarely signilied a true bloodstream infection in the analysis by Weinstein et al. of 1,585 positive blood cultures (1). A higher
proportion of viridans streptococci (38% of isolates) and CNS (12% of isolates) represented definite pathogens. The number of positive blood culture sets can also be used to interpret the significance of a positive blood culture. In two separate reports, Weinstein et al. (1,14) demonstrated that 75 to 100% of blood cultures collected from patients with true bacteremia are usually positive, while contaminants often grow in only one positive blood culture among several obtained. Although the number of positive bottles within a blood culture set has been suggested to be predictive of clinical significance, a recent publication demonstrated this is not useful information for distinguishing true infection from contamination with CNS (15). Determining the clinical significance of a blpod culture isolate is a subjective process without a “gold standard”; however, some clinical indicators occur significantly more often among patients with true bacteremia than those with contaminants. These include a leukocyte count of 220,OOOJpl or <4,OOO/ul, absolute neutropenia, hypotension, hypothermia (<36“(Z), and marked fever (>4O”C) (1). The optimal approach to interpreting the significance of a positive blood culture is a critical assessment of the patient’s clinical and microbiologic data by an infectious disease physician (16). This option is not available to most microbiology laboratories when deciding whether antimicrobial susceptibility testing (AST) should be done or how to determine the institution’s blood culture contamination rate.
Laboratory-Based Algorithms A generally accepted quality assurance goal is to keep the rate of blood culture contaminants below 3% of all blood cultures drawn. Unfortunately, discrete guidelines for identifying contaminants are scarce. In 1985, Archer
(17) suggested that clinical microbiology laboratories should report CNS isolates that were likely contaminants accordingly and not perform susceptibility tests unless requested by the patient’s physician. The following scenarios were delineated as “highly suggestive” of contamination with CNS: (i) one positive culture followed by negative cultures, (ii) one culture positive out of two cultures that were drawn simultaneously, (iii) two cultures growing CNS but separated by a time interval with more than one negative culture, and (iv) only one bottle positive out of an aerobic/anaerobic two bottle set (17). The last scenario can no longer be considered suggestive of contamination (15). Trevino and Mahon (18) acknowledge the difficulty in distinguishing pathogens from contaminants and suggest that “microbiologists cannot make this determination (true pathogen or contaminant) in the laboratory; physician input and patient history are needed.” They caution readers about considering any organism isolated from two or more blood culture bottles as a contaminant. As noted above, the number of positive bottles is not a reliable criterion for determining true pathogens (15). Forbes et al. (19) note the increasing difficulty associated with interpreting the clinical significance of blood cultures yielding skin flora organisms. They present the following laboratorybased criteria to assist in recognizing probable contaminants: (i) CNS, fl acnes, Corynebacterium spp., or Bacillus spp. isolated from “one of several cultures”; (ii) growth of more than one organism from “one of several cultures”; and (iii) an organism isolated from a blood culture that is different from “the organism causing the infection at a primary site of infection.” An obvious question is how close in time can the cultures with no growth be to the posi-
NOTE: No responsibility is assumed by the Publisher for any injury an&or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods. products, instructions or ideas contained in the material herein. No suggested test or procedure should be canied out unless. in the reader’s judgment. its risk is .justitied. Because of rapid advances in the medical sciences, we recommend that the independent verification of diagnoses and drug doses should be made. Discussions, views and recommendations as to medical procedures. choice of drugs and drug dosages are the responsibility of the authors. Cliuicnl Microbiology Newsletter (ISSN 0196-4399) is issued twice monthly in one indexed volume per year by Elsevier Science Inc., 655 Avenue of the Americas, New York. NY 10010. Subscription price per year: Personal: EUR 47 for customers in Europe; $6,300 for Japan; and US$S3 for all countries other than Europe and Japan. Institutional: EUR 306 for customers in Europe: WO.600 for Japan; and US$342 for all countries other than Europe and Japan. Periodical postage paid at New York. NY and at additional mailing offices. Posbnaster: Send address changes to C‘li,ricol Micmbrologv Newsletter; Elsevier Science Inc., 655 Avenue of the Ameticas. New York, NY 10010. For customer service, phone (212) 633-395@ TOLL-FREE for customers in the United States and Canada: I-88%4ES-INFO (I 888-437-4636) or fax: (2 12) 633-3860.
50
0196-4399 00 (see frontmatter)
0 2002 Elsevier Science Inc.
Clinical Microbiology
Newsletter 24:7.2002
Potential contaminant (coagulase-negative staphylococci, Corynebacterium spp., Propionibacterium acnes, Bad/us spp., Micrococcus spp., viridans streptococci) isolated from blood culture
Additional blood culture sets collected from the patient within 48 h show no growth
No other blood culture sets collected from the patient within 48 hr of the culture yielding a possible contaminant
Additional blood culture sets collected from the patient within 48 h positive with same organism I
L
group? I
Refer isolate to pathology resident to determine clinical significance
Report isolate as “probable contaminant” and do not perform susceptibility testing unless requested by patients physician
I
Classify isolate as a pathogen and perform susceptibility testing
Perform susceptibility testing
Figure I. Algorithm implemented at the Universily of Iowa to minimize the workup of blood culture contaminants
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Newsletter 24:7.2002
10 2002 Elsevier Science Inc.
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tive culture to still be considered part of the series. Some laboratories subscribe to the College of American Pathologists Q-Tracks program. Laboratories participating in Q-Tracks consider a blood culture contaminated if CNS, Colynebucterium spp., fl acnes, Bacillus spp., Micrococcus spp., or viridans (alphahemolytic) streptococci are isolated from “only one of a series of blood culture specimens” (20). The length of time between cultures considered part of a series is 124 h. Autopsy cultures and specimens obtained through indwelling vascular lines are excluded. This omission of catheter-drawn cultures could result in an underestimation of an institution’s contamination rate. At the University of Iowa, we recently developed and implemented an algorithm not only to identify blood culture contaminants but also to report them to clinicians as “probable contaminants.” By not performing AST on these isolates, more than $20,000 in annual microbiology charges have been deferred. Perhaps of greater importance, the report of “probable contaminant” instead of an AST may discourage unnecessary antimicrobial agent use. The reporting of AST results for contaminants likely promotes unnecessary antimicrobial use (typically vancomycin), resulting in increased pressure for the emergence of antimicrobial resistance and higher pharmacy expenditures. The algorithm implemented at the University of Iowa is used when a skin flora organism is isolated from a blood culture and is based on the proportion of blood culture sets that are positive (Fig. 1). The algorithm considers each blood culture set (an aerobic and anaerobic bottle inoculated with blood obtained from a single venipuncture or catheter) as a single entity. If one or more additional blood cultures were obtained within *48 h and all are negative at that point in time, the isolate is considered a contaminant. If no additional blood cultures were submitted, or there were additional blood cultures collected within ~48 h yielding the same organism, a pathology resident gathers relevant clinical data from the institution’s electronic information system and makes a judgment regarding the isolate’s significance (contaminant, indeterminate, or pathogen). The resi-
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dents are instructed to determine the clinical significance of selected blood culture isolates by considering a patient’s clinical history, leukocyte count, body temperature, number of positive blood cultures, culture results from other sites, radiographic data, histopathologic findings, and current status. A copy of the article by Weinstein et al. (1) was given to each pathology resident when the algorithm was implemented and microbiology laboratory faculty are available for consultation as needed. Physicians caring for patients are often contacted by pathology residents to discuss the clinical significance of isolates, especially prior to classifying an isolate as a contaminant. AST is performed only on isolates classified as indeterminate or pathogens. Isolates of viridans streptococci are automatically considered pathogens when additional positive blood cultures yield the same organism. Occasionally, physicians request AST to be performed on isolates initially classified as contaminants. In the initial 8 months of algorithm use, this occurred with 9% of isolates that were automatically considered contaminants because of additional negative blood cultures. Because of opposition to the algorithm by neonatologists, all isolates of CNS from neonates are considered significant. To evaluate the accuracy of the algorithm-based assignments during the first 8 months the algorithm was in use, an independent retrospective chart review was performed. The algorithm was found to be acceptably accurate, with an overall PPV for identifying blood culture contaminants of 9 1.7%; the details of the algorithm evaluation are reported elsewhere (2 1,22). An added benefit to implementation of the algorithm in our laboratory was the opportunity to increase the involvement of pathology residents in clinical microbiology activities. The algorithm has become a useful tool to educate residents regarding the interpretation of positive blood cultures. Clinical microbiology laboratories without pathology residents available could use other individuals familiar with the issues of blood culture contamination to determine the clinical significance of selected blood culture isolates. Usually no more than 20 min are required to determine an isolate’s significance, and on average,
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only four isolates per week require investigation. Alternatively, a laboratory could consider all organisms isolated from additional positive blood cultures significant and investigate only isolates from patients with a single blood culture set submitted. It has been suggested that collection of only one blood culture set should be highly discouraged, not only because distinguishing contamination from septicemia is difficult, but because a single blood culture lacks sufficient sensitivity for detecting a bloodstream infection (7).
Conclusion Each microbiology laboratory should develop its own criteria for identifying contaminants within its institution. Consultation with infectious disease physicians when determining guidelines is essential. As guidelines are put into use, it is important to remain flexible and attempt to respond to questions and/or opposition by customizing the algorithm to meet individual patient and clinician needs. Once a reliable method for determining blood culture contaminants is in place, intervention can be targeted to units or individuals with elevated contamination rates. References 1. Weinstein, M.P. et al. 1997. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin. Infect. Dis. 24584-602. 2. MacGregor, R.R. and H.N. Beaty. 1972. Evaluation of positive blood cultures: guidelines for early differentiation of
contaminated from valid positive cultures. Arch. Intern. Med. 130:84-87. 3. Bates, D.W., L. Goldman, and T.H. Lee. I99 1. Contaminant blood cultures and resource utilization: the true consequences of false-positive results. JAMA 265:365-369.
Little, J.R. et al. 1999. A randomized trial of povidone-iodine compared with iodine tincture for venipuncture site disinfection: effects on rates of blood culture contamination. Am. J. Med. 107:119-125. King, T.C. and PB. Price. 1963. An evaluation of iodophors as skin antiseptics. Surg. Gynecol. Obstet. 116:361-365. Strand, C.L.. R.R. Wajsbort, and K. Sturmann. 1993. Effect of iodophor
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vs. iodine tincture skin preparation on blood culture contamination rate. JAMA 269: 1004-I 006. Weinstein, M.P. 1996. Current blood culture methods and systems: clinical concepts, technology. and interpretation of results. Clin. Infect. Dis. 23:40-46. Aronson, M.D. and D.H. Bor. 1987. Blood cultures. Ann. intern. Med. IO6:246-253. Bryant, J.K. and CL. Strand. 1987. Reliability of blood cultures collected from intravascular catheter versus venipuncture. Am J. Clin. Pathol. 88: 113-l 16.
positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients. J. Clin. M icrobiol. 36: l923- 1926. 13. DesJardin, J.A. et al. 1999. Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer. Ann. Intern. Med. 13 I:64 I-647. 14. Weinstein, M.P. et al. 1983. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev. Infect. Dis. 535-53.
IO. Tonnesen. A.. M. Peuler, and W.R. Lockwood. 1976. Cultures of blood drawn by catheters vs. venipuncture. JAMA 235: 1877.
IS. Mirrett, S. et al. 2001. Relevance of the number of positive bottles in determining clinical significance of coagulasenegative staphylococci in blood cultures. J. Clin. Microbial. 39:3279-3281.
I I. Felices, F.J. et al. 1979. Use of the central venous pressure catheter to obtain blood cultures. Crit. Care Med. 7:78-79.
16. Siegman-Igra, Y. and C. Ernst. 2000. Nosocomial bloodstream infections: are positive blood cultures misleading? Clin. Infect. Dis. 30:986.
12. Souvenir, D. et al. 1998. Blood cultures
17 Archer, G.L. 1985. Coagulase-negative
staphylococci in blood cultures: the clinician’s dilemma. Infect. Cont. 6:477-478. 18. Trevino, S. and CR. Mahon. 2000. Bacteremia, p. 1007. In C.R. Mahon and G. Manuselis (ed.), Textbook of diagnostic microbiology, 2nd ed. W.B. Saunders Company, Philadelphia. 19. Forbes, B.A. et al. 1998. Bloodstream infections, p.300. In B.A. Forbes, D.F. Sahm, and A.S. Weissfeld (ed.), Bailey & Scott’s diagnostic microbiology, 10th ed. Mosby, St. Louis. 20. College of American Pathologists. 2002. Laboratory Improvement Q-Tracks. wwwcap.ovg l/3/2002. 21. Richter, S.S. et al. Abstr. IO1st Gen. Meet. Am. Sot. Microbial., abstr. C65, p. 162,200l. 22. Richter, S.S. et al. Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm. (Submitted for publication.)
Case Report
Human Infection Caused by Monilt’ella suaveolens Shiwaji Pawar, M.D. Dennis Murray, M.D. Michigan State Universi@ East Lansing, MI
Walid Rhalife, Ph.D. Sparrow Hospital, Lansing. MI
Barbara Robinson-Dunn,
Ph.D.
William Beaumont Hospital Royal Oak, MI
Michael McGinnis,
Ph.D.
University of Te,sas Medical Branch at Galveston Galveston, TX
Opportunistic infections caused by uncommonly identified hmgi are increasingly recognized in humans and animals. Phaeohyphomycosis is a mycologic definition of growth of dematiaceous (dark-pigmented) fungi in tissue as hyphae, pseudohyphae, address: Dennis Murray, M.D., Pediatric Infectious Disease, Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48073-6769
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conidia, yeast cells, or any combination of these forms. Phaeohyphomycosis can be cutaneous, subcutaneous, or systemic. Systemic infections are least common. We report what we believe is the first human case of systemic phaeohyphomycosis caused by Moniliella suaveolens.
Case Report An 18-day-old Caucasian male infant was seen in the emergency department of a large community hospital with complaints of irritability and being inconsolable. An incarcerated right inguinal hernia was diagnosed. The hernia was manually reduced, and the infant was admitted to the hospital for further management, including elective surgery. The infant had been born at 37 weeks gestation to a 30-year-old G4P2 mother. The mother was healthy during the antenatal period, except that she was treated for bacterial vaginosis with metronidazole 3 weeks prior to delivery. There was no prolonged rupture of membranes. After birth, the baby
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became increasingly tachypneic and developed grunting respirations. He was transferred to the neonatal intensive care unit. where he was started on oxygen, cefotaxime, and ampicillin. A complete blood count (CBC), C-reactive protein (CRP), and blood culture were non-contributory. A chest X ray showed diffuse interstitial pneumonia with small bilateral pleural efYi.tsions. The infant was discharged to home after 72 h with an indwelling intravenous catheter to complete 10 days of parenteral cefotaxime and ampicillin therapy for presumed bacterial pneumonia. Following discharge, the baby was seen by his primary care physician, and a mass on the right side of his neck was found. This mass was later clinically diagnosed as a cystic hygroma. The infant underwent a bilateral inguinal hemiorrhaphy and excision of the cystic hygroma after hospital admission from the emergency department. The cystic hygroma was found to extend into the superior mediastinum. Surgery was reportedly well tolerated.
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