Review Article

Antibiotic prophylaxis in obstetric and gynaecological procedures:A review

Vanessa CLIFFORD and Andrew DALEY

Department of Microbiology, The Royal Childrens Hospital, Melbourne, Vic., Australia

Surgical site infections are a common complication of obstetric and gynaecological surgeries; up to 10% ofgynaecological patients undergoing an operative procedure will develop a surgical site infection. In surgeries with highrates of post-operative infection, antibiotic prophylaxis (using an antibiotic with an appropriate microbiologicalspectrum and administered in a timely manner) can play a major role in improving outcomes. This review examinesthe medical literature to assess the indications and appropriate antibiotic choices for prophylaxis to prevent surgicalsite infection in obstetric and gynaecological surgery. For some procedures, such as caesarean section, surgicaltermination of pregnancy and hysterectomy, antibiotic prophylaxis is clearly indicated. For other procedures, such asinsertion of an intrauterine device, medical termination of pregnancy and laparoscopy, antibiotic prophylaxis is usuallynot required. For several other procedures where the evidence for antibiotic prophylaxis is unclear or inadequate, wediscuss the current evidence for and against prophylaxis. Guidelines for infective endocarditic prophylaxis withsurgery are also discussed.

Key words: antibiotic prophylaxis, gynaecological surgery, obstetric surgery, surgical site infection.

Introduction

Surgical site infections (SSIs) are a common adverseevent in hospitalised patients;1 810% of gynaecologicalsurgery patients undergoing an operative procedure willdevelop an SSI.2 SSIs have been shown to increasemortality, readmission rate and length of hospital stay.3,4

Rates of infection vary according to the premorbidcondition of the patient, as well as surgical andanaesthetic factors.2

Appropriate and timely antibiotic prophylaxis hasbeen shown to be highly effective in reducing theincidence of SSI.5 Antibiotic prophylaxis is designed toreduce the microbial contamination of a wound duringsurgery to a level that will limit the opportunity forpost-operative infection. The need for antibioticprophylaxis depends primarily upon the likely risk ofwound contamination during surgery. In 1964, the USNational Research Council developed a SurgicalWounds Classification scheme.6 This scheme classifieswounds as clean, clean-contaminated, contaminated or

dirty-infected (SSI rates are 12%, 69%, 1320% and>40% without antibiotic prophylaxis respectively foreach type of wound).7 Owing to the high rates of post-operative wound infection with all but clean surgicalprocedures, administration of prophylactic antibiotics isuniversally recommended.8 Procedures that open thegenito-urinary tract are usually considered clean-contaminated. In addition, antibiotic prophylaxis is oftenrecommended for clean surgical wounds where theconsequences of post-operative infection will bedevastating.8 A variety of refinements to this riskassessment have been proposed, including the UnitedStates National Healthcare Safety Network Risk IndexScoring system, which takes into account additionalfactors such as patient health (American Society ofAnesthesiologists score) and duration of the operation(>75th percentile).A number of studies across a range of surgical

procedures have shown that there is a narrow window ofopportunity for the administration of effectiveantimicrobial prophylaxis.9 Antibiotics need to be presentin the tissue at the time of incision to be effective.10 Ingeneral, antimicrobial prophylaxis after wound closure isunnecessary as it does not provide additional benefit.11

and can lead to higher costs, morbidity and drive theemergence of resistant bacteria.12

It is rare in obstetric or gynaecological practice torequire additional doses of antibiotics beyond the initial

Correspondence: Dr Vanessa Clifford, Department ofMicrobiology, Royal Childrens Hospital, Flemington RoadParkville Victoria 3052, Australia.Email: vanessa.clifford@rch.org.au

Received 11 February 2012; accepted 9 May 2012.

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Australian and New Zealand Journal of Obstetrics and Gynaecology 2012; 52: 412419 DOI: 10.1111/j.1479-828X.2012.01460.x

Th e Australian and New Zealand Journal of Obstetrics and Gynaecology

dose administered at induction of anaesthesia. Moststudies comparing single with multiple dose strategiesdo not show a benefit,11,13 although these are notall restricted to obstetric and gynaecological procedures.In general, doses only need to be repeated if theoperation lasts longer than the half life of theantimicrobial agent.Reviews of surgical prophylaxis suggest compliance

issues in 3090% of cases owing to problems withantibiotic choice, dose and duration.14

Ideally, prophylactic antibiotics should cover thenarrowest spectrum or organisms possible to minimisethe development of bacterial resistance.15 For thisreason, it is important to consider the likely source ofpathogens in each type of surgery. For most infections thatoccur after obstetric or gynaecological surgery, the sourceof pathogens is the endogenous flora of the womansvagina or skin. The endogenous flora of the genital tract ispolymicrobial, consisting of anaerobes, gram-negativeaerobes and gram positive cocci (such as Staphylococciand Streptococci). In contrast, laparoscopic proceduresthat do not breach any mucosal surfaces are morecommonly contaminated with skin organisms only (usuallygram positive organisms such as Staphylococci).It should be noted that prophylactic antibiotics do not

need to cover every possible pathogen that may causeinfection. Decreasing the number of organisms present(the bacterial load) will usually enable the patientsimmunological defences to function adequately.Prophylaxis is also understood as being distinct from earlytreatment when clinical infection is present.Other factors to consider when choosing an appropriate

antibiotic for prophylaxis include low toxicity, anestablished safety record and the ability to reach aneffective concentration in the relevant tissue prior to theprocedure.1

Narrow-spectrum first-generation cephalosporins, suchas cephazolin, are used in preference to later generationagents, such as ceftriaxone, because the latter are strongdrivers of resistance in gram-negative bacteria and haveless activity against Staphylococci, a common cause ofpost-operative wound infection. Cephalosporins in generalhave no activity against Enterococcus spp., which may beof significance for intra-abdominal procedures where thebowel is breached. Comparisons of first and thirdgeneration cephalosporins in several trials have not shownsuperiority in preventing wound infection.16

Whilst allergies to b-lactam antibiotics are frequentlyreported by patients, the incidence of true IgE-mediatedallergy (urticaria, angioedema, bronchospasm) or seriousadverse reaction (such as drug fever and toxic epidermalnecrolysis) is rare. Rates are reported as between 1 and 4per 10 000 doses.17

Alternative agents include lincomycin/clindamycinand/or vancomycin. High rates of methicillin-resistantStaphylococcus aureus at an institution would influence thechoice of prophylactic antibiotic in favour of aglycopeptide such as vancomycin.

Obstetric Procedures

Caesarean section

Women who undergo caesarean section have a muchhigher risk of developing an infection compared withwomen who deliver vaginally.18 A 2010 Cochrane reviewfound conclusively that routine antibiotic prophylaxis forcaesarean section (in both elective and non-electivesettings) is effective in reducing SSI [relative risk (RR) forwound infection 0.39; 95% confidence interval (CI) 0.320.48]; the analysis included 77 studies and 11 971women.19 The timing of antibiotic prophylaxis was notspecifically addressed in the review.A second recent Cochrane review assessed whether

different classes of antibiotic are more (or less) effectivefor surgical prophylaxis. This review, whilst limited bypoor quality data, showed no overall difference inoutcome according to antibiotic class (e.g whencomparing penicillins and cephalosporins).20 None of thestudies looked at the outcome for the baby or maternalinfection after the initial post-operative stay. An exceptionshould be made for obese women, where there isemerging evidence that they have a higher risk of SSIpost-Caesarean section and may benefit from extendedspectrum antibiotic prophylaxis (e.g cephalosporin plusazithromycin).21

Studies have shown that single-dose antibioticprophylaxis is as effective as multiple doses ofantibiotic.13,22

Recent evidence suggests that antibiotics administeredprior to skin incision may further reduce the risk of post-operative infection.23 A meta-analysis in 2008 (thatincluded three randomised controlled trials; with a total of749 women) found preoperative administration ofantibiotic (compared with administration of antibiotic aftercord clamping) was associated with a 53% reductionin postpartum endometritis (RR 0.47; 95% CI 0.260.85).24 Other outcomes (wound infection and confirmedsepsis) did not reach statistical significance. Other largeretrospective cohort studies published since this 2008review have supported the finding of a reduction ininfectious morbidity with antibiotic prophylaxisadministered prior to skin incision.25,26 The meta-analysisof these RCTs did not differentiate between labouringand non-labouring women; it is therefore difficult tobe sure that these results apply equally to womenundergoing elective caesarean section. Interestingly, arecent prospective controlled trial did not find a benefitof pre-incision antibiotic prophylaxis compared withadministration after cord clamping in women undergoingelective caesarean section.27 In addition, no benefit forpre-incision antibiotic prophylaxis for elective caesareanswas found in a recent large study reporting on infectionrates using historical controls, after an institutional policychange.25

The benefit of administration of antibiotic prophylaxisprior to skin incision needs to be weighed againstpotential risks. To date, studies have shown that exposure

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of the infant to antibiotics (when administered prior tocord clamping) is not associated with an increase inneonatal sepsis, admission or length of stay in theNeonatal Intensive Care Unit.25,27,28 Other infantoutcomes were infrequently reported;19 in particular, nostudies reported on the incidence of oral thrush in babiesexposed to antibiotics. The long-term outcomes of infantexposure to antibiotics are not known.There is a very small risk of maternal anaphylaxis with

antibiotic prophylaxis and, if administered pre-cordclamping, may put the infant at risk. This minor risk islikely outweighed by the benefits, especially given thatantibiotic prophylaxis for Group B streptococcus isroutinely administered to a significant proportion oflabouring women.The currently available evidence suggests that all

women undergoing caesarean section should receiveantibiotic prophylaxis. A single dose administered in the30 min prior to skin incision for emergency caesareansections is appropriate (see Table 1).

Termination of pregnancy

Reported infection rates for first trimester surgicaltermination of pregnancy range from 0.01 to 2.44%;29

similar rates have been reported for second trimestersurgical termination of pregnancy.30 Cervicitis (caused byChlamydia trachomatis or Neisseria gonorrhoeae) is a riskfactor for postabortal infection.31 A Swedish cohort studyfound that the presence of chlamydia prior to terminationof pregnancy (in the era before antibiotic prophylaxis)conferred a 30-fold increased risk of salpingitis and a4-fold increased risk of endometritis.32

A meta-analysis of various antibiotic regimes showedthat antibiotic prophylaxis for surgical termination ofpregnancy reduces the risk of upper genital tract infection(RR 0.58; CI 0.470.71).33 Most of the studies includedin this meta-analysis had relatively high rates of sexuallytransmitted infections (STI) infections; the benefit ofuniversal prophylaxis in populations at very low risk isunclear.29

Both oral doxycycline31,34 and metronidazole31 havebeen shown to be effective in reducing the risk ofpostabortal infection. To maximise efficacy, antibioticprophylaxis should be administered before theprocedure.29

One study found that a screen and treat strategy fordetecting C. trachomatis was less cost-effective thanuniversal antibiotic treatment with doxycycline prior totermination of pregnancy.35 There are no randomisedtrials that compare single-dose antibiotic prophylaxis forC. trachomatis with a screen and treat approach.29 Therelative cost-effectiveness of each approach will clearlyvary according to the incidence of STIs in the population.The association between bacterial vaginosis (a complex

alteration of normal vaginal flora with overgrowth ofanaerobic organisms) and postabortal infection rates isnot clear. To date, there has been one trial of oral

metronidazole treatment of bacterial vaginosis (BV) priorto termination of pregnancy that demonstrated areduction in postabortal infection rates,36 whilst threeother trials have not demonstrated a statistically significantdifference in infection rates.29

For medical abortion, there are no randomisedcontrolled trials of antibiotic prophylaxis. The bestestimate of first trimester medical termination ofpregnancy infection rates is approximately 0.3%,29,37 withrates of serious infection estimated at approximately0.09%.38 A retrospective cohort study from the PlannedParenthood Federation of America suggests that thenumber needed to treat (NNT) with doxycycline (for1 week) would be 2500 to prevent one serious infection.38

Based on this estimate, antibiotic prophylaxis for medicalabortion is not warranted.

Manual removal of retained placenta

Manual removal of a retained placenta is required inapproximately 2% of deliveries39 and increases the risk ofbacterial contamination of the uterine cavity.40

Controversy exists over whether manual removal increasesthe risk of postpartum endometritis above that whichwould occur with vaginal delivery of the placenta. Elyet al.41 reported a retrospective cohort study involving1082 women which demonstrated that the incidence ofendometritis following manual removal of the placentawas 6.7% compared with 1.8% of women with normalplacental delivery (OR 2.9; CI 1.74.9). A 2006Cochrane review did not find any randomised trials thatevaluated whether antibiotic prophylaxis reduced the riskof infection with this procedure;40 no further randomisedtrials were identified in the published literature after 2006.On the basis of reported rates of endometritis in the

study by Ely et al., and until controlled studies becomeavailable, antibiotic prophylaxis for manual removal of aretained placenta is justified.

Third- and Fourth-degree vaginal tears

Severe perineal trauma occurs in 18% of vaginaldeliveries; it is more common with operative vaginaldelivery (especially when forceps are used) and/or midlineepisiotomy.42 Third- and fourth-degree tears involve theanal sphincter and thus give rise to a contaminated orclean-contaminated wound. Risks from perineal tearsinclude dyspareunia, incontinence and recto-vaginalfistula.43 A recent Cochrane review42 found only onerandomised controlled trial assessing the outcome ofantibiotic prophylaxis for third- and fourth-degree vaginaltears.44 This trial showed a reduction in post partuminfection rates (RR 0.34, 95% CI 0.120.96) withantibiotic prophylaxis, but was limited by earlytermination owing to difficulties in enrolment and someloss to follow-up.42,44

In the absence of definitive evidence from well-designedrandomised controlled trials, a pragmatic approach is to

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Table 1 Antibiotics for surgical prophylaxis

Surgery 1st lineLevel ofevidence64 Alternative Comments

ObstetricCaesarean section Cephazolin 1 g (adult

80 kg or more: 2 g) IV,before skin incision.

I Clindamycin600 mg IV

Antibiotics prior to skin incision reducematernal morbidity without affectingneonatal morbidity or mortality. Surgicalprophylaxis should be administered even ifthe patients has received Group BStreptococcal antibiotic prophylaxis duringlabour

Termination ofpregnancy (surgical)

Metronidazole 500 mg IV,ending the infusion at thetime of induction ANDDoxycycline 400 mg PO

I Clindamycin600 mgIV + Azithromycin

An alternative approach is to screen forC. trachomatis and bacterial vaginosis priorto ToP

Medical Terminationof pregnancy

Not indicated-level III-3

Manual removal ofplacenta

Metronidazole 500 mg IV,ending the infusion at thetime of induction ANDCephazolin 1 g (adult80 kg or more: 2 g) IV, atthe time of induction

III-3 Clindamycin600 mg IV

3rd and 4th degreevaginal tears

Metronidazole 500 mg IV,ANDCephazolin 1 g (adult80 kg or more: 2 g) IV

II Clindamycin600 mg IV

GynaecologicalHysterectomy Metronidazole 500 mg IV,

ending the infusion at thetime of induction ANDCephazolin 1 g (adult80 kg or more: 2 g) IV, atthe time of induction

I Clindamycin600 mg IVGentamicinORCefoxitin 2 g IV attime of induction

Patients should be screened and treated forbacterial vaginosis before hysterectomy

IUD insertion Not indicated IHysterosalpingographyor hysterosocopy orchromotubation forpatients with dilatedtubes or a history ofPID or tubaldamage

Doxycycline 100 mg bdfor 5 days +Metronidazole 500 mg IVsingle dose

IV Azithromycin 1 gorally

Hysterosalpingographyor hysterosocopy orchromotubation withno history of PIDand normal tubes onvisualisation

Not indicated IV

Endometrial biopsy Not indicated IVLaparoscopy Not indicated II

National Health and Medical Research Council Levels of Evidence.64

Level I: A systematic review of level II studies; Level II: A randomised controlled trial; Level III-1 A pseudo-randomised controlled trial;Level III-2 A comparative study with concurrent controls; Level III-3 A comparative study without concurrent controls; Level IV A caseseries with either post-test outcomes or pretest/post-test outcomes.

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recommend antibiotic prophylaxis on the basis of thewound type (contaminated) and the potential adverseoutcomes arising from an infection.

Gynaecological Procedures

Hysterectomy

The benefit of antibiotic prophylaxis in reducing post-operative infection is well established for both vaginal andabdominal hysterectomy,45,46 although it should be notedthat randomised trials of antibiotic prophylaxis forlaparoscopic total hysterectomy and laparoscopicallyassisted hysterectomy have not been performed.1

Multiple doses of antibiotic are not more effective thana single antibiotic dose prior to incision.47 No particularantibiotic has been shown to be superior.1 In the absenceof direct evidence on the appropriate choice ofprophylactic antibiotic, the practical approach is to choosea combination of antibiotics that cover the expectedmicrobial flora of the region.Bacterial vaginosis is a risk factor for infection after

hysterectomy. A randomised non-blinded controlled trialfound that treatment with rectal metronidazole for womenwith bacterial vaginosis significantly reduced the rates ofvaginal cuff infection post hysterectomy.48

The available evidence suggests that all patients shouldbe screened and treated for bacterial vaginosis prior toundergoing hysterectomy. Patients should receiveantibiotic prophylaxis for hysterectomy (including anantibiotic with an anaerobic spectrum).

Hysteroscopy, hysterosalpingography orchromotubation

Infection after hysterosalpingography (HSG) occurs in asmall number of women; reported rates are 1.43.4%.49,50

The risk appears to be far lower when the fallopian tubesare not dilated, although this data is from a retrospectivereview.49 Infections after hysteroscopic surgery arereported in 0.181.5% of cases.5153 In a study of 200women undergoing hysteroscopic surgery, three developedsevere pelvic infection; all three had a history of pelvicinflammatory disease (PID). A recent Dutch study ofhysteroscopy conducted in an outpatient setting inasymptomatic women with infertility found an infectionrate of 0.4% without antibiotic prophlaxis.54

Based on these studies, it is reasonable to recommendantibiotic prophylaxis for women with a history of PID orfor those with tubal damage noted at the time of theprocedure. Doxycycline is the usual recommended agentand is continued for 5 days to treat presumed PID.Single-dose azithromycin is an acceptable alternative.

Intra-uterine device (IUD) Insertion

The risk of PID because of the introduction of genitaltract organisms is six times higher in the first 20 days

after insertion of an IUD. The risk of IUD-associatedinfections is also significantly higher in women frompopulations where there is a high prevalence of STIs (314%).55

Whilst significant concern exists about the risk ofPID after IUD insertion, a 2001 Cochrane meta-analysis of four randomised trials found that there wasno evidence that antibiotic prophylaxis reduced the riskof PID.55 This included two trials conducted in areaswith a high prevalence of STIs, Kenya and Nigeria. Inthe Kenyan trial, which had the highest rate of STIs, abenefit was found with prophylactic antibiotics.56 It isalso important to note that all the women in theUnited States trial had been screened for STIs prior toIUD insertion.57

In addition, a well-defined complication associated withIUD use is infection with Actinomyces spp. The incidenceof cervical colonisation with these organisms increaseswith the duration of IUD use. Antimicrobial prophylaxisat the time of IUD insertion does not impact on the riskof future actinomycosis.55

Whilst at present, the cost-effectiveness of screening forSTIs prior to IUD insertion is unclear, it is reasonablethat women should be screened and treated for STIs priorto IUD insertion, because the risk of IUD-associatedinfection is higher in this group. Universal prophylaxis forIUD insertion is not indicated.

Laparoscopy

Laparoscopic surgery is usually clean surgery, with a lowinfection risk (no mucosal surfaces are breached). Asingle placebo-controlled randomised trial of antibioticprophylaxis for laparoscopic gynaecological surgery failedto find a benefit.1,58 At this stage, there is insufficientevidence to be certain of the benefits of prophylaxis forlaparoscopic surgery.

Other procedures: large loop excision of thetransformation zone (LLETZ) and midurethralsling procedures

For several other common gynaecological procedures,there is insufficient research evidence to determinewhether antibiotic prophylaxis is indicated.

Large loop excision of the transformation zone

Many women report vaginal discharge and bleeding afterLLETZ, but there is very little trial evidence forantimicrobial prophylaxis for LLETZ procedure.59 It isalso unclear whether discharge and bleeding isnecessarily attributed to infection. A single randomisedcontrolled trial did not find a difference in vaginaldischarge with routine administration of ofloxacinfollowing LLETZ.60 There are no trials of preoperativeantibiotic prophylaxis.

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Midurethral sling

Rates of infection (especially urinary tract infection) arerelatively high (~5.5%) after midurethral slingprocedures,61 suggesting that perioperative antibioticprophylaxis may be useful. There is, however, very littlehigh-quality research evidence to support this practice.Further evaluation is needed.

Prevention of infective endocarditis

The 2007 American Heart Association guideline found noevidence that administration of prophylactic antibiotics forgenitourinary procedures reduces the risk of infectiveendocarditis.62 For this reason, prophylaxis is generallynot recommended except for persons with heartconditions with the highest lifetime risk of endocarditis.These conditions includes a prosthetic cardiac valve,unrepaired cyanotic congenital heart disease (CHD),completely repaired CHD with prosthetic material ordevice in the first 6 months after the procedure,repaired CHD with a prosthetic patch or device andcardiac transplantation recipients who develop cardiacvalvulopathy.62

For these patients, prophylaxis with an antibiotic that isactive against enterococci (such as ampicillin orvancomycin) should be considered in addition to anyantibiotic that would otherwise be administered as routinesurgical prophylaxis in a healthy person.63

Conclusions

Infection occurs when the balance between host defencesand organism virulence are disturbed. In addition toprophylactic antibiotics, careful attention should be paidto other aspects of surgical care including meticulousskin antisepsis, aseptic surgical technique, avoidance ofshaving, management of chronic illness (e.g hypo-albuminemia, malnutrition) and maintenance of normo-glycemia and normothermia perioperatively, to furtherreduce the incidence of SSI.Prophylactic antibiotics are a very effective adjunct

in preventing SSI when used appropriately (seeTable 1). Attention should be paid to ensure that a lowtoxicity antibiotic with an appropriate spectrum ofactivity is administered in a timely manner prior tosurgery.It should be noted that prophylactic antibiotics may not

be necessary for some low-risk obstetric and gynae-cological procedures such as laparoscopy, IUD insertionor medical termination of pregnancy.

Conflicts of Interest and Financial

Disclosure

There are no conflicts of interest and no relevant sourcesof funding.

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