D U

An evaluation of antibiotic prophylaxis

in cardiac catheterization

Hllgh Clurk, M.D.”

Rochester, N. 1’.

ring cardiac catheterization the pro- longed presence and manipulation

of catheters in the heart may allow re- peated introduction of bacteria into the Ijlood stream. As most patients under- going this procedure have valvular or congenital heart disease, the induced bac- teremia ma>- predispose the patients to bacterial endocarditis. Maximal attention to sterile technique and the use of prophy- lactic antibiotics are measures wide11 recommended to decrease the risk of endo- carditis.‘-”

The purpose of this report is threefold: (1) to determine the incidence of bacteremia in adults undergoing cardiac cntheteriza- tion; (1) to dcfne the bacteria to which the patient is exposed during catheteriza- tion; and (3) to evaluate the effectiveness of prophylactic antil)iotic-s in preventing bactercmia.

Methods and material

All adult patients admitted to Strong l\lemorial Hospital for cardiac catheteri- zation over a nine month period (August, 1966, through April, 1967) \vere assigned by a randomization method to one of two protocols for preparation for catheteriza- tion. The protocols were identical with the exception that Group A patients re- ceived four tloses of proc;tinV penis-illin,

600,000 units intramuscularly, every 1 hours, beginning 15 minutes to one hour before catheterization. If a patient gave in history of penicillin allergy, ervthromycin, 250 mg. by mouth, \vas substituted. This regimen has been standard in the hospital for many years. Patients assigned to Group I3 received 120 antibiotics before or after catheterization. A mimeographed protocol sheet \vas placed with each patient’s chart on the day prior to catheterization by the cardiolog> resident lmt all orders were actually lvritten in the order book I)!- tile medical intern. Although the study pro- tocol ~-as explained to the house staff prior to beginning the study, 23 patients as- signed to the antibiotic group did not re- ceive antibiotics prior to catheterization and this deviation from the protocol may represent a bias on the house staff’s part. These patients are henceforth included in (koup H, and this deviation explains why Group H is larger than Group A. T\YO patients originally assigned to Group B inadvertently received antibiotics before catheterization and are included in (;roup A. Thirty-two patients received penicillin, seven received erythromycin, and S3 t-e- ceived no antibiotic.

Blood cultures were taken directI>. from the catheters by the operator who lx-as gowned, masked, and gloved. Approxi-

‘llis stucly was n~~~ported iu [urt by Grants III< 3966, III< 5500. and TI-.\I-2X. litlited States Public Ilealtlc Service. \Vasllington. 11. C.

Received for publication Oct. 10. 1968. *Formerly Medical Chief Resident. Strong Memorial Hospital, Rochester. N. Y.

I,yol. ii, No. 6, pp. i67-ii.1 J~ruc, 1969 American Heart Journal 767

768 Clark

ruately 5 ml. of I)lood were \vithdrau-n md discarded hefore drawing the specimen for culture into sterile, individually mmpped disposa1)le sq’ringes. The operator n-orked in a draped sterile field and did not handle the recording instruments although it is unlikely tllat the environment approached the relative stcrilitl- of an operating room. The final culture \vas frequently taken 1)). ;t go\vned, masked, and gloved radiologist in a different room, and it DYLS considered that in this portion of the pro- cedure contamination \ws most dificult to control.

Four cultures \\.ere requested during each catheterization procedure. The first culture ~2s taken from the rig11 t heart itnmediat el>. after recording the pulntonar) artery pressure. The second culture \vas taken from the left heart after transseptal passage of the catheter. The third culture ~~1s taken from an intra-arterial needle or cmnula after the determination of the c;irdiac output \vas completed. The final culture \~;Is taken from the left heart catheter just lIefore its renioval. The specinlens \\.ere immediately. injected into flamecl titrated I)ottles and delivered to the microhiolog) lal)oratcq.. Aliquots I\-ere placed in tq.pticase so)’ broth and thiogl\.- colate I)rntll, and a pour plate was made. (‘ultures \\.ere incubated at 37” C‘. for 5 days, and if negative, the I)roths \\‘ere sul)- inoculated into blood agar. I f no g-o\\-th uxs seen on the I)lood agar in 24 hours, the cultures \\‘ere discarded. Al1 isolates \\.ere considered as significant. J’cnicil- linase uxs added to all 1)lood specimens taken from patients \~llo received penicillin.

Coniplications follavirig catheterizations I\-ere tabulated and a long-term folio\\--up made \vhenever possible. If a temperature greater than 38” C‘. \\-a~ recorded in ;L patient during the 4X hour period following catlietcriz~~tion, ii tliorougll examination \ms perfomed for signs of infection, and 1)lood cultures \vere again dr;l\\,n.

Results

Tlje 122 patients admitted for cardiac catheterization \\.ere included in the study. Although the t\\m groups \\.ere unequal in size for reasons given above, there \\-a no statistically- siguificant difference between the groups \\-it11 respect to age, sex, under-

lying heart disease, and duration of tllc‘ procedure (Table I).

Positive cultures \\-ere obtained in 7 of 39 (1X per cent) of Group A patients alid 12 of X3 (14.5 per cent) of Group H pa- tients (TnI)le II). The difference vx not statisticall>- significant 114. chi square ;it~- al!rsis. Ko patient had more than one positive culture. Of 438 cultures taken, 19 (4.3 per cent) \\‘ere positive, and (~\\Y) cu- tures contained tm’o organisnjs. The follrtll cultuw \\‘a~ positive in 10 of 89 speciulwS ( 11.2 per cent) taken and \\ lien coiiipawd with the freclucnc~ of positkit, in 111~5 first tlirce specimens, tliis \\.as unlikr~l~~ to llave occurred 115’ cl1a11ce alone (l‘al)l(

III). ‘I’\vmt)-one organisnis \I-ere isolated

from 19 positive cultures. Sf0phylocmrlf.~ CI//II~.S nx the most common species found and accounted for 76 per cent of the posi- tive crlltures (l’nljle I\:). Diphtheroids \vcre present 011 three oc-casions. Strrrinir

lutcvr and an anaerobic. spore former \vew each isolated once. H\- the disk method. 8 of 16 staphv1ococca1 iso1ates \\.erc re- sistm t to penicillin, I)ut 13 of 13 tested \\+tli ii~clhicillin \\.ere sensitive. Sensitivi- ties of other organisms to these and to ot1lc.r nntil)iotics are SIJOM~ in ‘I’al>lc I\-.

I )uririg folio\\--up examination in the hospital, 12 of 39 (31 per cent) of C;roup A patients and 22 of X3 (26 per cent) of (Group 13 patients had a temperature elevatiou during the 48 Ilours suhsequerit to catheterization (‘l‘al~le I I). Houxwer, all cultures taken at the time of tempera- ture elevation \vere sterile. l;ever occurred

‘I otal patient5 39 83 ‘l’c,txl blood cultures l-40 198 .\vcrnge no. of c’i~ltlire-;

per patient 3 6 3.6 I’.ltiellt> with positive

ctlltclrei 7 12

1’~ cent of patierlts \vith poiitive cllltrlrci 18.0 14 5

I’er cenf of cultures positive 6.1 4 0 Per cellt of patients with

fever after cntheteriza- tiw 31.0 26 0

*:\ntibiotic beiore catheterization. tNo antibiotic hriore ratlwterimtion.

in 6 of 10 (31.6 per cent) of patients \\.ilo had positive cu1tures taken at tlIe time of catheterization and in 33 of 303 (32 per cent) of pa&n ts \\.I10 had negative cul- tures at catheterization (‘I’atjle III). Kane of these differences are of statistical sig- nificance.

LVllen a chart revimv MXS made one month after termination of tJlc study, 48 patients Ilad undergone either cardiac surgery or postmortem examination. Evi- dence of endocarditis \vas found in n single patient and is discussed belo\\-.

Discussion

Although antibiotic prophylaxis has lIeen widely recommended in preparation for cardiac catheterization, veq. little in-

formation has I)een availal)le, indicating the risk of exposure to Imcteremia during the procedure. Kriedberg and C’hernoffd demonstrated L)acteremia in 4.5 per cent of children I\-ho received penicillin Ilefore catheterization and 4.7 per cent of those \vlio received no antil)iotic lIefore catll- eterization. Altllough the method of as- signment to treatment and control groups was not given, the difference uxs not sig- nificant. Lyon and (Gould” found IMC- teremia present during cardiac ratheteri- zation in 18 per cent of adult patients given antibiotics and in 17 per cent of tliose not given antil)iotics Ijefore the pro- cedure. Neither of these tm.0 studies dem- onstrated a difference in fever follom.ing catheterization I)etween the t\\-0 groups. The increase in frccluency of positive

7‘~~hle I\‘. Organisms isolated elf ccztheterizcztion and antibiotic sensitivity

, Pen Mefh Erythro Chloro T&a .5Wp

OrgrznisnL Toad (no./ (no./ (no./ (no.1 (no./ (no./ 1 ~ Cvpk .IVZP (no.,~ (ncr.,l

total) lotul) total) total) total) fold) t&d) , totui I

Stnphylor-orrus ulbu$ 16 8/16 13/13 16116 16/16 12116 lO/l.Z lO/lO 517 1)iphtheroids 1 l/l l/1 l/l l/l 1/l iXil>* NI) l/l “Anaerobic spore former” 1 O/l o/ 1 NI) l/l l/l l/l l/l l/l

Snrcina 1 uleu 1 h-D

19

.%bbreviations: Pen. Penicillin; Meth. methicillin; Eryttrro, erythromycin; Chloro. chloramphenicol; Tetm. tetracycline; Strep. strepto- mycin; Ceph, cephalothin: Amp, ampicillin.

*h’II). Not determined.

770 Clark

cultures in adults may be due to the longer duration of the procedure which often includes troth left and right heart catheteri- zation as welt as extensive angiocardio- graphic studies.

The study reported here supports the previously reported nork in that it fails to demonstrate protection from transient I)acteremia \vitti the use of prophylactic antibiotics. The incidence of positive cut- tures in adults with and without prophy- tactic antibiotics agreed closely with the findings reported by Lyon and Gould. As in previous studies, febrile reactions fot- towing cardiac catheterization were equatl> common in treatment and control groups, and were not caused by demonstrable infection. Other possible sources of fever include pyrogen on catheters, sensitivity. to angiocardiographic materials, and in- ttammation at the sites of catheter in- troduction.

Furthermore, the bacteriologic data pre- sented here demonstrate that patients were at greatest risk from the introduction of Stuphylococcus albus, and that 50 per cent of the strains isolated here lvere resist,- ant to penicillin. Staphylococci were also the most frequently isolated organisms from blood taken at catheterization in the previous studies. Although no antibiotic sensitivity studies \vere reported, it is likely that penicillin resistance \voutd have been comn1on. Thus, penicillin %voutd not be the drug of choice if it were felt neces- sary to give an antibiotic prior to cath- eterization with the goat of preventing subsequent endocarditis. Ttle choice of penicillin 1)~ those recommending anti- biotic ~vas probably predicated on the assumption that t-hose organisms most commonly causing endocarditis in genera1 \voutd be the organisms to which the pa- tient \vould receive most exposure during cardiac catheterization, and that is not the case.

The statistically significant increase in frequency of positive cultures taken at the end of catheterization suggests that the duration of the procedure may increase the risk of bacteremia. As noted above, however, it was felt that the final culture \\XS least protected from contamination, and a causal relationship between duration of procedure and increased incidence of

positive culture wntiot IX tirnitv dra\\.rl. That t)acteremin is mw-e wnlnlon~in ;kdults tllan children undergoing (.~~tlleteriz;ctioll ma>- also be explained 1)~ the finding oi more frequent positive c‘uttiires in n1ow ~)rolonged procedures.

No c‘ases of endocarditis following c.,tth- eterization were detected in the follo\v-u1) examinations of 566 patients studied I)>. the authors of the tl1.o earlier studies d antibiotic prophylaxis. In the stud!, w- ported here, 48 of 122 patients underwent cardiac surgery or postmortem examina- tion subsequent to their cardiac catheteri- zation. Evidence of endocarditis lb-as found in a single patient examined six lveeks following cardiac surgery for placement of an aortic graft and prosthetic aortic vatw. N~isscvitr prrfltrva was isolated from blood cultures taken during life, and the demon- stration of 3 vegetation on the prosthetic v;dve ring at autopsy ruled out- endocardi- tis acquired as a result of ttacteremia SLIS- tained during catheterization.”

A review of the literature indicates tllat endocarditis associated with cardiac cattl- eterization is distinctly ~~nusuat, if not rare. 111 several recent rwir\vs of endo- carditis in over 500 paliwts, cardiac cath- eterization teas not Illcntioned as a pre- disposing cvent.7-“’ Iial)ino\-ich” has t-e- ported ;L single ease and Pankey” thrctc cases of endocarditis folton-ing cathet.eri- zatioti, 1111 t inadequate Iw~teriologic ‘11~1 clinical details \vere giwti 10 evaluate 1 Iic likelihood of a causative association. 14s the organisnis isolated at ~‘nttieterizatiori are not comlnon causes of endocarditis. knowledge of the infecting organisnls ill the cases of Pankey and Rat Gnovich \~oulci 1~2 instructive.

The lack of association of endocarditis and cardiac catheterization gains further support froni reviews of complications of catheterization performed in over 16,000 patients by three groups of authors.‘“-‘” Although the duration of follow-up exanli- nations were not given, no cases of endo- carditis I\-ere detected in the large experi- ence cited.

Summary

The incidence of bacteremia during cardiac catheterization was studied in 122 adult patients and the protective &w-t- of

;Intil)iotic prophylaxis was evaluated in treatment and control groups. Antibiotic prophylaxis did not decrease the incidence of transient bacteremia at cardiac cath- eterization. Staphylococci were the orga- nisms most frequently isolated from blood cultures taken at catheterization and 50 per cent of the staphylococci were resistant LO penicillin. A review of the literature suggests that endocarditis as a sequel to cardiac catheterization is a rare event, and may not justify the use of potentially sensitizing agents for prophylaxis.

The author expresses his appreciation to Drs. I’aul N. Yu, Bernard E. Schreiner, and Gerald W. >lurphy for allowing this study to be done on pn- tients referred to them for cardiac catheterization, .md to Mrs. Helen Short of the bacteriology labora- I or)’ for technical assistance.

Zimmerman, 11. A.: Intravascular catheteriza- tion, Springfield, Ill., 1959, Charles C Thomas, Publisher, chap. 1, p. 5. Wood, P.: Diseases of the heart and circulation, ed. 2, Philadelphia, 1957, J. B. Lippincott Co., p. 180. ITriedberg, C. K.: Diseases of the heart, ed. 3, Cambridge, 1966, Harvard [Tniversity Press, p. 108. Kriedberg, hl. E., and Chernoff, H. I..: Ineffec- tiveness of penicillin prophylaxis in cardiac catheterization, J. Pediatrics 66:286, 1965. Gould, L., and LJ-on, A. F.: Penicillin prophy- laxis cardiac catheterization, J. A. R/I. A. 202:210, 1967.

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