APPLIED MICROBIOLOGY, Nov. 1974, p. 778-784Copyright i 1974 American Society for Microbiology

Vol. 28, No. 5Printed in U.S.A.

In-Use Contamination of Intravenous Infusion FluidDENNIS G. MAKI,I ROGER L. ANDERSON, AND JONAS A. SHULMAN

Center for Disease Control, Atlanta, Georgia 30333, and the Department of Medicine, Emory University Schoolof Medicine, Atlanta, Georgia 30322

Received for publication 22 August 1974

During the 1970 to 1971 nationwide epidemic of septicemias caused byEnterobacter cloacae and Enterobacter agglomerans traced to intrinsic contami-nation of Abbott intravenous infusion products, 94 infusion systems manufac-tured by Baxter Laboratories were studied microbiologically and epidemiologi-cally during hospital use. Intravenous fluid from 10 systems (11%) containedmicroorganisms, usually Staphylococcus or Bacillus species; one infusion was

heavily contaminated with Klebsiella pneumoniae. No national epidemicorganisms, E. cloacae or E. agglomerans (formerly Erwinia), were recovered,suggesting that during this period frequent contamination with these organismswas unique to Abbott's infusion products. Contamination in this study appearedto be extrinsic in origin (introduced during clinical use) and related to the dura-tion of continuous intravenous therapy. Nine of 61 systems (15%) that had beenused longer than 48 h were contaminated, whereas only 1 of 33 used less than 48h (3%) contained microorganisms. This study and the recent national outbreakindicate that contamination of infusion fluid, both from intrinsic and extrinsicsources, must be recognized as an additional risk of intravenous therapy; how-ever, a once-daily replacement of the delivery apparatus can significantly dimin-ish this hazard.

Between summer 1970 and March 1971, manyU.S. hospitals experienced outbreaks of intrave-nous (i.v.)-associated septicemia with Entero-bacter cloacae and Enterobacter agglomerans,ultimately traced by the Center for DiseaseControl to intrinsic contamination of infusionproducts manufactured by Abbott Laboratories(7, 12, 16, 17; E. J. Fisher, D. G. Maki, J. Eisses,T. R. Neblett, and E. L. Quinn, Progr. Abstr.Intersci. Conf. Antimicrob. Ag. Chemother.,11th, Atlantic City, N. J., p. 20, 1971). E. ag-glomerans, formerly designated Erwinia (11), amember of the herbicola-lathyri group and morecommonly known as a plant-associated bac-terium, had been anuncommonhuman pathogenin the past and rarely isolated from blood(27, 29). In early 1970, Abbott introduced intouse a new, Elastomer-lined screw-cap closurefor i.v. bottles. Over 40% of cap assemblies fromseveral thousand bottles of warehouse stocksampled were found to contain microbial con-tamination with a large variety of organisms,including the epidemic strains E. cloacae andE. agglomerans (7, 17; D. C. Mackel, D. G.Maki, R. A. Anderson, F. S. Rhame, and J. V.Bennett, Progr. Abstr. Intersci. Conf. Anti-microb. Ag. Chemother., 11th, Atlantic City,

I Present address: Infectious Disease Unit, University ofWisconsin Hospitals, Department of Medicine, University ofWisconsin Medical School, Madison, Wisc. 53706.

N.J., p. 20, 1971). Culture surveys of Abbotti.v. systems during clinical use in two hospitalsduring the epidemic had disclosed up to 25%rates of fluid contamination; E. cloacae and E.agglomerans were recovered from multiple in-fusions (17). In January and February 1971, be-fore the source of contamination of Abbott'sfluids was identified as intrinsic, present withinthe system from its manufacture, culturestudies of other manufacturers' i.v. fluids wereundertaken to (i) find if epidemic organisms E.cloacae and E. agglomerans were also presentin infusion products other than Abbott'ssampled during hospital use, (ii) determine themagnitude of in-use contamination of i.v. fluidin hospitals which did not use Abbott infusionproducts and also had not experienced out-breaks, and (iii) gain knowledge of the epi-demiologic variables influencing contamination.(This study was presented in part at the AnnualMeeting of the American Society for Micro-biology, Minneapolis, Minn., May, 1971.)

MATERIALS AND METHODSBackground. The institution selected for study,

Grady Memorial Hospital, is a 1,500-bed acute caremunicipal hospital located in downtown Atlanta, Ga.,and is staffed by house officers and faculty fromEmory University School of Medicine. Its InfectionsCommittee conducts periodic prevalence surveys of

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nosocomial infection (1). Outbreaks or even isolatedinstances of septicemia attributable to contaminatedinfusion fluid have not been detected. At the time ofthe study, infusion products manufactured by BaxterLaboratories had been used exclusively for 10 years.Parenteral products were delivered to the hospital,stored in central supply, and delivered to patient careunits on a weekly basis. All devices for venouscannulation, both steel needles and plastic catheters,were inserted by ungloved house officers or medicalstudents after cutaneous disinfection with 70% alco-hol or an iodophor. Thereafter, the nursing staffprovided all maintenance care of i.v. infusions, withthe exception of direct i.v. injections of medications.No formal protocol or other written policy governedinsertion of i.v. cannulae or day-to-day managementof i.v. therapy. As in virtually all American hospitalsat that time (7, 16), administration sets were notroutinely replaced, including when the cannula waschanged; replacement usually only followed frankmalfunction such as leakage or impeded flow. Also, nospecific precautions such as gloves or application ofdisinfectants to the delivery apparatus were employedduring initial set-up and subsequent manipulation ofinfusion systems.

Epidemiologic methods. Five general medicalwards, each with an attached intensive care unit, foursurgical wards, and the pediatric unit were selectedfor study. Over a 3-day period in January 1971 each ofthe wards was visited at least once, making anattempt to culture every available i.v. infusion on theward. For each infusion, the specific types of bottles,solutions, administration sets, volume-control reser-voirs, connectors, stopcocks, manometers, and otherequipment constituting the delivery apparatus werenoted; the entire system was inspected for evidenceof malfunction, particularly leakage or inadequacy ofinterposed equipment, gross contamination, blood,particulate matter, or turbidity within the fluid. Theinfusion site was uncovered, and the type of cannulaand any malfunction such as infiltration or leakagewas recorded. The site was carefully examined forevidence of inflammation (phlebitis). Phlebitis wasdefined as the presence of two or more of the follow-ing: erythema, increased warmth, tenderness to pal-pation extending beyond the cannula tip, edema, or apalpable cord. In addition, the lengths of time thatthe current cannula had been in place and thesampled i.v. bottle had been hanging and how longthe patient had received continuous, uninterruptedi.v. therapy were obtained from the nurse's label onthe bottle, the patient record, or direct inquiry of theward nurses. All i.v. medications, both added directlyto the bottle (additives) or injected into the infusionline, were recorded. All clinically recognizable orculture-proven infections, any potential sites of infec-tion, such as urethral catheterization or intratrachealintubation, and all major medical diagnoses werenoted.

Microbiology. After inspection, the entire deliv-ery apparatus was removed for sampling when 200 mlor less remained within the bottle. When two bottlesfed the same infusion site (a dual system), the adminis-tration set that had been in longest continuous use

was sampled. The bottle and administration set wereremoved in toto, and a sterile cap was placed over thedistal end of the administration set tubing. It was notlogistically possible to remove and culture cannulaeas part of this study. The bottle and attachedadministration set were immediately transported tothe laboratory in a sterile plastic bag for microbiologi-cal sampling. Approximately two-thirds of the sys-tems were sampled in a laminar flow hood at theCenter for Disease Control and the remaining one-third in a quiet, minimally occupied laboratory withinthe hospital.

For sampling of fluid (2; Mackel et al., Progr.Abstr. Intersci. Conf. Antimicrob. Ag. Chemother.,11th, Atlantic City, N.J., p. 20, 1971), the sterile capwas removed from the distal end of the administrationset tubing, and the end was flamed and attached to abacteriological field monitor (Millipore Corp.; meanpore size 0.45 Mm). The 10- to 12-ml contents of theadministration set were filtered under negative pres-sure through the monitor. If antimicrobial agents hadbeen administered through the set, after filtration ofi.v. fluid, the membrane filter was washed by filtering100 ml of sterile 0.9% saline. The filter was removedfrom the plastic holder and placed aseptically onto aplate of Trypticase soy agar containing 5.0% sheep'sblood, which had been premoistened with 0.2 ml ofbrain heart infusion broth enriched with 0.5% beefextract. After incubation at 37 C for 72 h, all morpho-logical colony types present were subcultured andmicrobiologically identified by methods and criteriain use at the Center for Disease Control. Platesnegative for growth at 72 h were further incubated at25 C for 5 days before discarding. The entire contentsof 50 500- and 1,000-ml unopened bottles of fluid,randomly selected from the study wards, were sam-ples in a similar manner. Also, 50 administration setsfrom hospital stock were cultured by infusing en-riched brain heart infusion broth through the set andincubating the broth at 37 C for 48 h.

RESULTSDuring the 3-day periods, 94 infusions from 89

patients were microbiologically sampled. Fluidfrom the administration set of 10 (11%) yieldedmicrobial contaminants (Table 1). No patientbecame septicemic with organisms similar tothose isolated from his infusion. Contaminationrates were comparable among medical andsurgical patients; no pediatric i.v. systems werefound contaminated, although only nine weresampled. No clustering of contaminated infu-sions by ward, day of study, location of sam-pling (hospital laboratory or Center for DiseaseControl), or product lot number was observed.As seen in Table 2, staphylococci, Staphylo-

coccus epidermidis or Staphylococcus aureus,were isolated from 8 of the 10 positive systems;Escherichia coli and Klebsiella pneumoniaewere each recovered from one infusion. Only theinfusion containing K. pneumoniae was heavily

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contaminated, i.e., confluent growth on themembrane filter, indicating a level of contami-nation exceeding 30 organisms per ml. All of theother positive systems yielded only very lownumbers of organisms, ranging from one to sixper administration set. Cultures of the 50 uno-pened bottles and unused administration setswere negative for microbial growth.

Severity of underlying illness, age, or sex didnot influence contamination. Table 3 lists someof the clinical variables which were analyzedseeking an epidemiologic association with con-tamination of fluid. Peripheral sites of infec-tion, fever, bottle additives or i.v. medications,antibiotics (i.v. or non-i.v. route), type of i.v.fluid, and type of cannula showed no correla-tion. Phlebitis, malfunction of the infusionapparatus, and interposition of a three-waystopcock into the infusion line were all consider-

TABLE 1. Prevalence of contaminated infusion fluidand phlebitisa

No. withNo. of contami- No. with

infusions nated phlebitisfluid

Medicine ............ 66 8(12) 18(30)Surgery ............. 19 2 (11) 11 (58)Pediatrics ............. 9 0 0

a The presence of phlebitis could not be evaluatedin seven patients. Numbers in parentheses indicatepercentage.

TABLE 2. Microbiologic profile of contaminated i.v.fluid

Study no. Organisms cultureda (p 10 ml)

3 Coagulase-neg. S. aureus5 110 Coagulase-neg. S. aureus (1)c

S. epidermidis (1) 5Bacillus spp. (3)

13 Coagulase-neg. S. aureus 120 Coagulase-pos. S. aureus 1726 Coagulase-neg. S. aureus 133 Coagulase-neg. S. aureus 155 S. epidermidis 159 E. coli 465 Klebsiella pneumoniae TNTCd68 S. epidermidis (5)

Micrococcus (1) 6

a By Millipore filtration.Anerobic fermentation of 1% mannitol and pig-

ment production (4, 6).cNumber of organisms of each isolate (in paren-

theses) in instances of mixed contamination.d TNTC, Too numerous to count; confluent growth

on Millipore filter.

ably more frequent in contaminated systems.Over two-thirds of study patients had active orpreviously active peripheral infections whichdid not appear to influence the microbiologicalstatus of their infusion, with the exception ofthe two patients with gram-negative bacilluscontamination of fluid who both had previousperipheral infections with organisms taxonomi-cally similar to those subsequently isolatedfrom their i.v. fluid. Unfortunately, the isolatesfrom these infections were not available forsubtyping and comparison with the strainsisolated from fluid. The mean number of hoursthat bottles of sampled systems had been hang-ing and of continuous venous cannulation didnot differ significantly between contaminatedand noncontaminated systems. However, themean duration of uninterrupted infusion incontaminated systems, 5.3 days, significantlyexceeded that of noncontaminated systems, 3.7days (P < 0.05). Only 1 of 33 systems (3%) incontinuous use less than 48 h contained micro-

TABLE 3. Epidemiologic features of intravenousinfusions studied

No. of No. of

Feature systems systemsnoncon- contami-taminateda nateda

Infusion sampled.84 10

Peripheral site of infection ...... 58(69) 7 (70)

Fever ( > 101 F) ................ 23(28) 3 (30)

Phlebitis .................... 24(29) 5 (50)

Additives in bottle ............. 57 (68) 5 (50)

Antibioticsi.v........................... 42 (50) 5(50)Any route ............ .. 54 (64) 7 (70)Glucose-containing fluid ..... 73(87) 9(90)System malfunction ......... 29 (35) 5 (50)Three-way stopcock .......... 47 (56) 8 (80)

CannulaeScalp vein needle ........... 20 (24) 3 (30)Plastic catheter .............. 55 (65) 7 (70)Central venous pressure

catheter .................. 8 (10) 0

Duration + SEMWBottle (h) ................... 13.0 ± 1.3 15.7 + 4.6Cannula (h) ................. 40.8 ± 3.2 53.9 ± 8.1Continuous i.v. therapy

(days) ... ..... .... 3.7 ± 0.3 5.3 + 1.3c

a Total at risk for some of the variables is less than the totalnumber of infusions sampled. Numbers in parentheses indi-cate percentage.

° SEM, Standard error of the mean.cP < 0.05.

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organisms, whereas 9 of 61 (15%) which hadinfused for more than 48 h were colonized(Table 4; P = 0.063).

Infusion phlebitis could be assessed in 87infusions (Table 5). Phlebitis, present in 29(32%7o), did not correlate with the type of i.v.solution administered, system malfunction,contamination of fluid, or i.v. medications, withthe exception of antibiotics. Phlebitis accompa-nied 42% of all antibiotic infusions, usually ofpenicillin, cephalothin, ampicillin, or nafcillin,whereas only 22% of infusions without i.v.antibiotics led to phlebitis (P < 0.05). Type ofvenous cannula also significantly influencedphlebitis: no phlebitis was noted in 23 patientsreceiving infusion therapy through scalp veinneedles, whereas phlebitis was present in 29(45%) of 64 patients receiving fluids throughplastic catheters (P < 0.001). With plasticcatheters, the rate of phlebitis was correlatedstrongly with the duration of cannulation; phle-

TABLE 4. Relationship of duration of infusion therapyand in-use contamination of infusion fluid

Continuous infusion No. of systems No. with fluidtherapy (h) at risk contaminationa

<48 33 1(3)>48 61 9 (15)b

a Numbers in parentheses indicate percentage.b P = 0.063 by Fischer's exact test.

TABLE 5. Relationship of type of cannula, duration ofcannula placement, and intravenous antibiotics to

infusion phlebitis

Factor" No. of No. with Pvale'Factora systems at phiebitidrisk"b hebts

CannulaPC 64 29 (45)SVN 23 0 <0.001

PC placement24 h 18 025 to 48 h 21 10 (48)>48h 25 19 (76) <0.005

i.v. antibioticsNo 40 9 (22)Yes 47 20 (42) <0.05

a PC, Plastic catheter; SVN, scalp vein needle." Phlebitis could not be assessed in seven systems.cPresence of two or more of following: palpable

cord, local tenderness, heat, redness, or edema. Num-bers in parentheses indicate percentage.dBy Fischer's exact test or chi-square test with

Yates correction.

bitis complicated 76% of catheterizations ex-ceeding 48 h and only 26% of those less than 48 h(P < 0.005). The prevalence of phlebitis on thesurgical service, 58%, considerably exceededthat on medicine, 30%; however, only 1 of 19surgical infusions employed scalp vein needles,whereas these devices were used in one-fourth ofmedical infusions. With infusions through plas-tic catheters, the rates of phlebitis on the twoservices were similar.

DISCUSSIONNo epidemic organisms, E. cloacae or E.

agglomerans, were isolated from the 94 infu-sions of Baxter i.v. products sampled duringclinical use. Three comparable surveys of Ab-bott products in two hospitals between Decem-ber 1970 and February 1971 showed 17 to 25%rates of in-use contamination and 2 to 5%positivity for the epidemic strains (17). Thus, itappeared, based upon this sample, that duringthis period, i.v. fluid contamination with E.cloacae and E. agglomerans was much morefrequent with Abbott's products. This conclu-sion was further substantiated by a prospectivecomparative study of in-use Abbott and Cutterinfusion products within a single hospital (17).Although initial culture surveys of unused Ab-bott fluids had been inconclusive (7, 17; Fisheret al., Progr. Abstr. Intersci. Conf. Antimicrob.Ag. Chemother., 11th, Atlantic City, N.J., p.20, 1971), the seeming absence of epidemicorganisms in the infusion products of two othermajor manufacturers during that period was amajor influence in directing an even moreexhaustive and ultimately successful search foran intrinsic source of Abbott fluid contami-nants.The observed prevalence of in-use contamina-

tion in this study, 11%, is impressively high andwould probably have been even higher had theentire fluid contents of each infusion beensampled, i.e., fluid within the bottle as well asadministration set and both halves of dualinfusions. Negative cultures of unused fluidsand delivery apparatus suggests that the sourceof contamination was extrinsic, i.e., microorga-nisms were introduced into the infusion duringor after setup for use and also were unlikely tohave been a consequence of the sampling proc-ess.

Contamination of infusion fluid from extrin-sic sources has very likely caused sporadicsepticemias for as long as i.v. therapy has beenemployed (10, 16, 18, 24, 25); however, such in-fections have for the most part remained un-recognized or have been attributed to the can-

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nula. Wilmore and Dudrick reported sevencontaminated systems of 220 in a study ofin-line Millipore filters, but did not report*microbiological identities or quantitative levelsof contamination (30). Deeb found that 3.8% of236 in-use bottles of conventional i.v. solutioncontained microorganisms, most likely of ex-trinsic origin (9), and Duma et al., in July 1970,identified four septicemias related to in-usecontamination of infusion fluid and discoveredthat 35% of in-use i.v. administration sets intheir hospital were contaminated, many withmore than one organism (10). However, Abbottfluids were used in this latter study, and it isimpossible to assess the extent to which theresults might have been influenced by unidenti-fied intrinsic contamination. In both of theaforementioned studies, quantitative samplingmethods were not employed. In a universityhospital investigation, in February 1971, werecovered microbial contaminants from 6.8% of148 Cutter systems sampled during clinical use;the profile of contamination, both microbiologi-cally and quantitatively, was similar to thatfound in this study (17). In that study as in thisone, contaminants appeared to be of extrinsicorigin, related to the many manipulations ofinfusion apparatus which occur in the course ofi.v. therapy, such as attachments of the admin-istration set, addition of medications to thebottle, injections into the tubing, manometricmeasurements, and handling of the cannula.Three independent studies of commercial infu-sion fluid which was cultured immediately afterintroduction of additives in the hospital phar-macy, but before delivery to patient care units,found 3.0 to 17.7% rates of contamination (3, 19;L. J. Hak, J. L. Long, R. L. Ruberg, and H. L.Flack, Annu. Meet. Amer. Soc. Hosp. Pharm.,1971). Our experience and all of these studies,and the growing number of reported outbreaksof infusion-related sepsis (7, 8, 10, 12, 22, 25;Fisher et al., Progr. Abstr. Intersci. Conf. An-timicrob. Ag. Chemother., 11th, Atlantic City,N.J., p. 20, 1971; Report of the committeeappointed to inquire into the circumstances,including the production, which led to the use ofcontaminated infusion fluids in the DavenportSection of Plymouth General Hospital, HerMajesty's Stationery Office, London, 1972),strongly emphasize that contamination of infu-sion fluid, especially from extrinsic sources, isrelatively common and now must be recognizedas an additional hazard of i.v. therapy.Intravenous systems in continuous use

beyond 48 h incurred a considerably greater riskof contamination, 15% (Table 4), suggestingthat the risk of introduced contamination is

cumulative. It is noteworthy that this criticalinterval of uninterrupted infusion, beyondwhich contamination rises sharply, is identicalto the critical period which has been statisti-cally established by multiple independent stud-ies for catheter-tip contamination and catheter-related sepsis (16). Michael and Ruebner firstdemonstrated (18), and we have confirmed, thatmicroorganisms capable of growing in infusionfluid, once introduced into an in-use system,can perpetuate in the administration set formany days despite serial replacements of thebottle and high rates of fluid flow (16, 17). Inthis country in the past, administration setshave not been routinely changed and haveusually been replaced only when they malfunc-tioned or became sufficiently dirty to becomeaesthetically offensive.Organisms recovered from in-use fluid, espe-

cially Staphylococcus and Bacillus species, arerecognized skin commensals. Gram-negative or-ganisms have been recovered with high fre-quency from the skin of patients (23) and fromthe hands of up to 40% of hospital personnelrandomly sampled (26). An outbreak of fiveKlebsiella pneumoniae i.v.-associated sep-ticemias in an intensive care unit was linked tocontaminated nurses' hand lotions (21). In ourstudy, peripheral infections with organisms tax-onomically similar to strains later isolated frominfusion fluid twice preceded in-use fluid con-tamination and suggests an increased risk ofi.v.-fluid-related infection in patients with anestablished active infection. Such a hazard hasbeen confirmed with catheter-associated sepsis(5, 20). Manual contact with the infusion appa-ratus by medical personnel is probably themajor mechanism of microbial ingress to fluidand possibly even the cannula wound (16). Theurgent necessity for frequent hand washing byphysicians and nurses cannot be emphasizedtoo strongly.The fact that the only heavily contaminated

infusion among the 10 culture-positive systemsyielded K. pneumoniae is not unexpected.Enterobacter species and to a lesser extentKlebsiella and Serratia, all members of thetribe Klebsielleae, predominated in the recentnational outbreak (7, 12; Fisher et al., Progr.Abst. Intersci. Conf. Antimicrob. Ag. Chemo-ther., 11th, Atlantic City, N.J., p. 20, 1971), andalso in other reports of sepsis traced to contami-nated fluid (10, 18, 25). We have found thatmembers of this tribe possess a selective abilityover other more common nosocomial pathogensto proliferate in glucose-containing i.v. solu-tions at room temperature (17). Fifty-onestrains, twice-washed to remove organic nutri-

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ents, inoculated into 5% dextrose-in-water andincubated at 25 C attained a mean 24-h concen-tration of over 105 organisms per ml. In contrast,50 of 51 clinical isolates of Staphylococcus,Pseudomonas, Proteus, Escherichia, andHerellea did not grow or more commonly died.These studies have subsequently been con-firmed by other investigators (12, 13, 14). Thus,in septicemias suspected to be due to contami-nation of infusion fluid, infection with one ormore members of tribe Klebsielleae should beexpected and, after discontinuing the infusion,antimicrobial therapy, when clinically indicated,should be chosen for bactericidal activity againstthese organisms.

Realizing a cumulative risk of in-use contam-ination of fluid, which increases significantlyafter 48 h of continuous infusion, and the abilityof many common hospital pathogens in fluid toamplify contamination logarithmetically within24 h, it is recommended that all infusion appa-ratus down to the cannula (bottles and adminis-tration sets) be routinely changed every 24 h,and at each change of cannula, all equipment betotally replaced. Several hospitals institutingthis control measure in the recent nationaloutbreak noted decreased epidemic septicemias(7, 12, 16, 17; Fisher et al., Progr. Abstr.Intersci. Conf. Antimicrob. Ag. Chemother.,11th, Atlantic City, N.J., p. 20, 1971). Theefficacy of this simple measure in diminishinginfections consequent to intrinsic contamina-tion of fluid augurs for its consideration toprevent infections caused by extrinsically intro-duced organisms.The higher frequencies in this study of phlebi-

tis in patients cannulated over 48 h, with plastici.v. catheters, and receiving i.v. antimicrobialagents known to cause venous inflammation,are in accord with previous epidemiologic stud-ies of infusion phlebitis (15, 28). A relationshipbetween microbial contamination of fluid andphlebitis was not demonstrated, possibly be-cause of the limited number of systems sam-pled. However, during the national epidemic,we found that in septicemias due to contami-nated fluid, infusion phlebitis, often dispropor-tionately severe, was present in 50% of cases;patients briefly cannulated, for less than 24 hand in many instances only with steel needles,suffered severe phlebitis (7, 16, 17).

ACKNOWLEDGMENTSThe expert technical assistance of Donald C. Mackel and

Bruce T. Wood is acknowledged.

LITERATURE CITED

1. Adler, J. L., and J. A. Shulman. 1970. Nosocomialinfections and antibiotic usage at Grady Memorial

Hospital. South. Med. J. 63:102-105.2. American Public Health Association. 1960. Standard

methods for the examination of water and waste water,11th ed. American Public Health Association, Inc.,New York.

3. Arnold, T. R, and C. D. Hepler. 1971. Bacterial contami-nation of intravenous fluids opened in unsterile air.Amer. J. Hosp. Pharm. 28:614-619.

4. Baird-Parker, A. C. 1963. A classification of micrococciand staphylococci based on physiological and biochem-ical characteristics. J. Gen. Microbiol. 30:409-427.

5. Bernard, R. W., W. M. Stahl, and R. M. Chase. 1971.Subclavian vein catheterizations: a prospective study.II. Infectious complications. Ann. Surg. 173:191-200.

6. Branson, D. 1968. Identification of Micrococcaceae inclinical bacteriology. Appl. Microbiol. 16:906-911.

7. Center for Disease Control. 1971. Nosocomial bac-teremias associated with intravenous fluidtherapy-U.S.A. Morbid. Mortal. Weekly Rep.20(Suppl).

8. Center for Disease Control. 1973. Septicemias associatedwith contaminated intravenous fluids. Morbid. Mortal.Weekly Rep. 22(11):99-100.

9. Deeb, E. N., and C. A. Natsios. 1971. Contamination ofintravenous fluids by bacteria and fungi during prepa-ration and administration. Amer. J. Hosp. Pharm.28:764-767.

10. Duma, R J., J. F. Warner, and H. P. Dalton. 1971.Septicemia from intravenous infusions. N. Engl. J.Med. 284:257-260.

11. Ewing, W. H., and M. A. Fife. 1971. Enterobacteragglomerans. The herbicola-lathyri bacteria. Center forDisease Control, Atlanta, Ga.

12. Felts, S. K., W. Shaffner, M. A. Melly, and M. G.Koenig. 1972. Sepsis due to contaminated intravenousfluids: epidemiologic, clinical and laboratory observa-tion of an outbreak in one hospital. Ann. Int. Med.77:881-890.

13. Gelbhart, S. M., G. F. Reinhardt, and H. B. Greenlee.1973. Multiplication of nosocomial pathogens in intra-venous feeding solutions. Appl. Microbiol. 26:874-879.

14. Guynn, J. B., D. M. Poretz, and R. J. Duma. 1973.Growth of various bacteria in a variety of intravenousfluids. Amer. J. Hosp. Pharm. 30:321-325.

15. Jones, P. F. 1951. Thrombophlebitis following intrave-nous infusions. Postgrad. Med. J. 33:444-447.

16. Maki, D. G., D. A. Goldman, and F. S. Rhame. 1973.Infection control in intravenous therapy. Ann. Int. Med.79:867-887.

17. Maki, D. G., F. S. Rhame, D. A. Goldmann, and G. L.Mandell. 1973. The infection hazard posed by contami-nated intravenous infusion fluid, p. 76-91. In A. C.Sonnenwirth (ed.), Clinical and laboratory aspects ofbacteremia-a symposium. Charles C Thomas Co.,Springfield, Ill.

18. Michaels, L., and B. Ruebner. 1953. Growth of bacteria inintravenous infusion fluids. Lancet 1:772-774.

19. Miller, W. A., G. L. Smith, and C. J. Latoilais. 1971. Acomparative evaluation of compounding costs andcontaminations rates of intravenous admixture sys-tems. Drug Intel. Clin. Pharm. 5:51-60.

20. Mogensen, J. V., W. Fredericksen, and J. K. Jensen.1972. Subclavian vein catheterization and infection: abacteriologic study of 130 catheter insertions. Scand. J.Infect. Dis. 4:31-36.

21. Morse, L. J., H. L. Williams, F. P. Grenn, E. E. Eldridge,and J. R. Rotta. 1972. Septicemia due to Klebsiellapneumoniae originating from a hand cream dispenser.N. Engl. J. Med. 277:472-473.

22. Phillips, I., S. Eykyn, and M. Laker. 1972. Outbreak ofhospital infection caused by contaminated autoclavedfluids. Lancet 1:1258-1260.

23. Pollack, M., P. Charache, R. E. Nieman, M. P. Jett, J. A.

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http://aem.asm

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Reinhardt, and P. H. Hardy. 1972. Factors influencingcolonisation and antibiotic-resistance patterns ofGram-negative bacteria in hospital patients. Lancet2:668-671.

24. Robertson, M. H. 1970. Fungi in fluids-a hazard ofintravenous therapy. J. Med. Microbiol. 3:99-102.

25. Sack, R. A. 1970. Epidemic of Gram-negative organismsepticemia subsequent to elective operation. Amer. J.Obstet. Gynecol. 107:394-399.

26. Salzman, T. C., J. J. Clark, and L. Klemm. 1968. Handcontamination of personnel as a mechanism of cross-infection in nosocomial infections with antibiotic-

APPL. MICROBIOL.

resistant Escherichia coli and Klebsiella-Aerobacter, p.97-100. Antimicrob. Ag. Chemother. 1967.

27. Starr, M. P., and A. K. Chatterjee. 1972. The genusErwinia: enterobacteria pathogenic to plants and ani-mals. Annu. Rev. Microbiol. 23:389-426.

28. Thomas, E. T., W. Evers, and G. B. Racz. 1970. Postinfu-sion phlebitis. Anesth. Analg. 49:150-159.

29. VonGravenitz, A. 1970. Erwinia species isolates. Ann.N.Y. Acad. Sci. 174:436-443.

30. Wilmore, D. W., and S. J. Dudrick. 1969. An in-line filterfor intravenous solutions. Arch. Surg. 99:462-463.

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