Journal of Perinatology (2017) 37, 16–20
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved 0743-8346/17
www.nature.com/jp
COMMENTARY
Optimal administration of cefazolin prophylaxis for cesarean
delivery
A Duffield1, P Sultan2, ET Riley3 and B Carvalho3
Journal of Perinatology (2017) 37, 16–20; doi:10.1038/jp.2016.210
INTRODUCTION
Cesarean delivery is the single most important risk factor for
developing postpartum infection.1 Surgical site infection (SSI),
including wound infection and endometritis, remains a significant
cause of morbidity and mortality in the obstetric population
undergoing cesarean delivery.2–3 Anti-microbial prophylaxis, the
most important factor in preventing SSI, significantly reduces the
risk of postcesarean fever, wound infection, endometritis, urinary
tract infection and serious bacterial infection.4 For the primary
focus of this review, we conducted a PubMed literature search
with the terms ‘pharmacokinetics’, ‘cefazolin’ and ‘pregnancy’ on 9
April and 13 September 2016. We identified 17 publications
(including 1 corrigendum). A critical review by two authors found
that 6 were not related to the topic and 1 was a review, leaving 10
original research articles (Table 1). Additional papers were selected
as appropriate to supplement the narrative parts of the review of
cefazolin in pregnancy. At the conclusion of this review, we
provide up-to-date recommendations for anti-microbial prophy-
laxis dosing alterations in the setting of cesarean delivery.
MINIMUM INHIBITORY CONCENTRATION
For anti-microbial prophylaxis to be effective, serum and tissue
antibiotic concentrations must exceed the minimum inhibitory
concentration (MIC) for susceptible bacteria before incision. To
prevent superficial, deep and organ SSI, we should aim for
antibiotic concentrations above MIC in skin, subcutaneous tissue,
fascia, muscle, amniotic fluid and myometrium. These therapeutic
levels should be maintained for at least the duration of surgery.5
PAST AND PRESENT RECOMMENDATIONS FOR
ANTI-MICROBIAL PROPHYLAXIS
In 2002, the Centers for Medicaid and Medicare Services and
Centers for Disease Control and Prevention recommended
administration of anti-microbial prophylaxis o1 h before surgical
incision (and 2 h for patients receiving vancomycin or fluroquino-
lones) as part of the performance measures outlined in the
National Surgical Infection Prevention Project (SIP).6 The following
year, these recommendations were reiterated in the comprehen-
sive Surgical Care Improvement Project.6 In 2013, the American
Society of Health-System Pharmacists, together with the Infectious
Diseases Society of America, the Surgical Infection Society and the
1
Department of Anesthesiology, Sentara Martha Jefferson Hospital, Charlottesville, VA, USA; 2Department of Anaesthesia and Perioperative Medicine, University College London
Hospital, London, UK and 3Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA. Correspondence: Dr AT
Duffield, Department of Anesthesiology, Sentara Martha Jefferson Hospital, 500 Martha Jefferson Drive, Charlottesville, VA 22911, USA.
E-mail: adrienne.duffield@gmail.com
Received 26 July 2016; revised 7 October 2016; accepted 14 October 2016
Society for Healthcare Epidemiology of America, further recom-
mended that the dose of cefazolin for cesarean delivery anti-
microbial prophylaxis should be 2 g for women weighing
o120 kg and 3 g for those weighing 4120 kg.7
For decades, it was recommended that anti-microbial prophy-
laxis for cesarean delivery be administered after umbilical cord
clamping, because of concerns regarding neonatal drug
exposure.3 However, more recent evidence demonstrated
increased efficacy with antibiotic dosing before incision rather
than after cord clamping without compromising neonatal safety.8
These data led to the ACOG recommendation of 1g of intravenous
cefazolin administered within an hour before surgical incision,
or 2 g in obese patients (body mass index (BMI) 430 kg m−2 or
4100 kg).9 There is evidence that alteration in the ACOG
guidelines for cesarean delivery anti-microbial prophylaxis may
have reduced the incidence of endometritis, thus potentially
reducing morbidity and mortality in the obstetric population.10
However, data from the literature suggest that the ACOG
antibiotic dosing guidelines for cesarean delivery are too low.
They do not reflect recent recommendations by the American
Society of Health-System Pharmacists for increased dosage for
general surgical patients. In addition, physiologic changes of
pregnancy may affect pharmacokinetics and pharmacodynamics
of anti-microbial prophylaxis drugs, and cesarean delivery patients
may require even larger doses of antibiotics than general surgery
patients.
PREGNANCY-INDUCED CHANGES IN CEFAZOLIN DOSING
Physiologic changes during pregnancy (such as increased renal
blood flow, glomerular filtration, increased total body water,
altered protein binding and decreased plasma albumin concen-
trations) alter the pharmacokinetics of cefazolin,11–13 and there-
fore may impact its efficacy and subsequent SSI risk. It is important
to consider and account for pregnancy-induced pharmacokinetic/
pharmacodynamic alterations in drugs when prescribing medica-
tions. The unique physiologic changes of pregnancy, including
increased volume of distribution (12.0 versus 6.9 L in non-
pregnant women)11 and glomerular filtration rate (increasing by
50% by the first trimester),12 influence drug levels of cefazolin in
pregnant women. Although initial data were conflicting,14–15
subsequent studies suggest that renal clearance of cefazolin may
be increased by up to twofold in pregnancy.11–16 Despite these
marked differences in drug elimination during pregnancy, ACOG
anti-microbial prophylaxis for cesarean delivery recommendations
are currently modeled on SSI prevention guidelines for the general
surgical population, without dose or timing adjustments account-
ing for differences in pregnant women.
 Cefazolin prophylaxis for cesarean delivery
AT Duffield et al
17
Table 1. Relevant articles identified by PubMed literature search with the terms ‘pharmacokinetics,’ ‘cefazolin’ and ‘pregnancy’

Author, ref. Pregnant Patients (n) Dose MIC Timing relative to Key findings
Controls (n) incision

Young et al.31 26 2g 4 μg ml − 1 — Both 2 and 3 g doses result in adipose tissue concentrations

N/A 3g above MIC in obese women
Swank et al.34 28 3g 8 μg ml − 1 30–60 min All obese women and 71% of morbidly obese women receiving
29a 2g 3 g cefazolin reached adipose cefazolin concentrations 4MIC
Only 20% of obese women and no morbidly obese women
receiving 2 g achieved MIC
Elkomy et al.16 20 1g 8 mg l − 1 60 min Cefazolin clearance increases in pregnancy. Doses larger than 1 g
N/A are required to maintain concentrations 4MIC for the duration of
cesarean delivery
van Hasselt et al.37 96 2g 4 mg l − 1 8 hourly for A semiphysiological model may have improved predictive
41b 2 days performance
Smits et al.13 30 — — — Cefazolin protein binding varies significantly between pregnant
43 women, neonates and non-pregnant adults. Higher unbound
40 (neonates) drug was found in pregnant women and neonates compared
with non-pregnant adults
Pevzner et al.32 29 2g 4 μg g − 1 30–60 min A large percentage of obese and extremely obese did not achieve
N/A MIC in adipose samples at skin incision (20 and 33%) or closure
(20 and 44%)
Grujic et al.19 45 2g 8 μg ml − 1 10 min Plasma cefazolin concentration was 4MIC immediately after and
4 6 h following cesarean delivery
Allegaert et al.11 49 2 g 0.5–4 mg l − 1 8 hourly for Cefazolin clearance estimates are twice that of non-pregnant
4 2 days adults. Maternal to fetal compartment equilibration half-time
decreases with increasing gestational age
Popovic et al.14 18 2g — 10 min Average concentration of prophylactic antibiotics are higher in
4 pregnant vs non-pregnant patients
Fiore Mitchell et al. 18
26 1 g 0.5 μg ml − 1 30, 60, 120, 240 Rapid attainment of concentrations 4MIC in maternal, cord and
N/A and 360 min amniotic fluid compartments
Abbreviations: MIC, minimum inhibitory antibiotic concentration for susceptible bacteria; N/A, not applicable. Controls are non-pregnant adults, unless stated
otherwise. aHistoric controls. bProspective controls.

Antibiotics exhibiting pregnancy-altered pharmacokinetics are
well described.17 While initial pharmacokinetic data demonstrated
cefazolin concentrations above MIC at the time of delivery in
patients receiving only 1g before elective cesarean delivery,18
subsequent studies suggest that current dosing of cefazolin for
cesarean delivery may be inadequate. Philipson et al.15 reported a
57% increase in cefazolin clearance in the antepartum compared
with postpartum period. A prospective study evaluating pharma-
cokinetics following the administration of 1g cefazolin in women
undergoing cesarean delivery found that cefazolin clearance was
increased by 74% compared with expected non-pregnant
values.16 While a dose of 2 g of cefazolin results in target tissue
concentrations above MIC for at least 6 h following
administration,19 computer simulations of cord blood (as a
surrogate for target tissue) determine that the probability of
maintaining free cefazolin concentrations above a therapeutic MIC
of 8 μg ml− 1 for susceptible Gram-positive bacteria is o 50%
when cefazolin is administered in doses o2 g.16
Administration of 2 g provides optimal maternal and cord blood
target level attainment rates while keeping neonatal levels within
clinically approved limits.16 These findings emphasize that the
current ACOG dosing recommendations of 1 g cefazolin for
cesarean delivery may not predictably result in adequate tissue
concentrations of cefazolin for the duration of surgery.16 Single-
dose therapy is effective in the majority of patients undergoing
uncomplicated cesarean delivery; however,8 in prolonged cesar-
ean delivery, redosing may be necessary. Pharmacokinetic data
suggest that because of increased drug clearance related to
pregnancy, redosing every 3 h may be preferable compared with
the 4 h recommended in the non-pregnant population.16 This
increase in dose and frequency of administration may be required
to compensate for accelerated elimination of cefazolin in
pregnancy and to preserve maternal drug plasma concentrations
and therapeutic duration (i.e., time that antibiotic levels within the
blood remain above MIC).
PREINCISION TIMING OF ANTI-MICROBIAL PROPHYLAXIS
ADMINISTRATION
There is clear evidence that antibiotics should be administered
before incision for cesarean delivery10 and that administration
460 min before surgical incision increases incidence of SSI.5 At
present, the controversial issue is whether we should narrow the
optimal window for anti-microbial prophylaxis administration. In
2004, the National Surgical Infection Prevention Project produced
an updated advisory statement summarizing their previous
recommendations for administration of anti-microbial prophylaxis
within 60 min.5 The authors further specified that antibiotics
should be given as close to the incision time as possible to
prolong the duration of therapeutic concentration and minimize
SSI rates.5 Since that time, several large trials have attempted to
address the issue of optimal timing of anti-microbials.20 Two large
prospective multicenter trials involving 1922 and 4472 surgical
patients, respectively, suggest that the lowest SSI rates occur
when anti-microbial prophylaxis is given within 30 min before
surgical incision.21–22 In a retrospective study of anti-microbial
prophylaxis timing and SSI at 112 US Veterans Affairs Hospitals,
data from 32 459 patients who had orthopedic, gynecological,
colorectal or vascular surgery demonstrated lower SSI rates in
patients receiving antibiotics within 60 min of surgical incision
compared with 460 min of incision.23 Furthermore, generalized
additive modeling demonstrated that the closer antibiotics are
given to the time of incision, the lower the risk of subsequent SSI.
In contrast to the above studies, a large observational study
involving 3836 patients undergoing consecutive non-obstetric
surgical procedures demonstrated greater efficacy (using

© 2017 Nature America, Inc., part of Springer Nature. Journal of Perinatology (2017), 16 – 20
 Cefazolin prophylaxis for cesarean delivery
AT Duffield et al
18
multivariable logistic regression analyses) of anti-microbial
prophylaxis administered 30 to 60 min before surgery compared
with 1 to 30 min.24 These results should, however, be interpreted
with caution as they are findings from the non-pregnant
population, and are in contrast to the expected pharmacokinetic
behavior of cefazolin. The 2013 American Society of Health-
System Pharmacists guidelines indicated that while available
evidence in the general surgical population suggests that a
window of 1 to 30 min may be optimal, the lack of robust data
prevented a recommendation of anything other than the currently
quoted 1 to 60 min window before incision.7
No studies specifically exploring the optimal window for anti-
microbial prophylaxis administration have been performed in the
obstetric population. Best available pharmacokinetic data suggest
that peak serum concentrations of cefazolin occur within minutes
of administration and decline steadily thereafter.16–27 Highest
maternal blood concentrations of cefazolin occur in the first
30 min after dosing, with ~ 20% probability of attaining MIC at 1 h
after 1 g cefazolin and ~ 70% after 2 g cefazolin.16 These results
are consistent with the increased clearance of this renally
eliminated drug in pregnant patients, and suggest that a shorter
preincision dosing window is required to compensate for
accelerated cefazolin elimination in pregnancy. A dosing window
closer to the time of surgery would preserve drug plasma Figure 1. A summary of adipose tissue levels of cefazolin after skin
concentration and allow MIC to be maintained for the duration incision and before skin closure during cesarean delivery from five
of surgery. Theoretically, the further away from the time of surgical different studies in obstetric patients.31–35 All investigators mea-
incision cefazolin is administered, the more likely the intraopera- sured cefazolin concentrations using high-performance liquid
tive drug concentrations will be below MIC in maternal tissues, chromatography, with the exception of Pevzner et al.,32 who used
microbiological agar diffusion assay. The dotted line at 8 μg g− 1
particularly during lengthy surgery. However, the time to effective represents the therapeutic MIC for susceptible Gram-positive
penetration of intravenous cefazolin to skin, subcutaneous tissues, bacteria. Results are clustered by body mass index (BMI) and
deep tissues and organs has not been fully elucidated and this cefazolin dose. Owing to non-uniform reporting, data are reported
equilibrium time may affect drug efficacy when administered at as means or medians consistent with what was reported in the
the time of surgical incision. On balance, evidence suggests that original paper. Stitely et al.33 enrolled women with BMI 435 kg m −2.
administration closer (1 to 30 min) to the time of incision may be For this graph, their data were grouped with the BMI group
preferable. 440 kg m−2 . Young et al.31 and Maggio et al.35 enrolled patients
with BMI over 30 kg m−2. Their data were included in the BMI group
30 to 40 kg m−2. Timing of cefazolin dose varied among studies.
CEFAZOLIN DOSING ALTERATIONS IN OBESE PREGNANT Young et al.31 dosed cefazolin within 30 min of incision, Pevzner
et al.32 and Swank et al.34 within 30 to 60 min before incision,
PATIENTS Maggio et al.35 within 60 min before incision and Stitely et al.33 via
Obesity has reached epidemic proportions. The World Health rapid intravenous ‘push’ on average 12 min before incision.
Organization estimates that 1.6 billion adults worldwide are
overweight and 400 million are obese. In the United States, 35% of
women of reproductive age are obese (BMI 430 kg m −2).28 Anti-
Stitely et al.33 found subcutaneous incision site concentrations
microbial dose adjustment should be carefully considered in this
consistently above MIC at the time of skin incision and skin closure
subset of obstetric patients, as SSI is more common in obese
in obese patients even receiving the same 2 g dose as in the
parturients undergoing cesarean delivery,29–30 and every 1 kg m−2
Pevzner et al.32 study, suggesting that timing of cefazolin
increase in BMI is associated with 13.8 μg ml− 1 lower plasma
concentration of cefazolin up to 8 h after initial dosing.31 Several administration in relation to the time of surgical incision may
recent studies have addressed the pharmacokinetics of cefazolin have an important role in its efficacy. Patients in the Stitely et al.33
in obese parturients. Figure 1 shows the tissue levels of cefazolin study were given antibiotics as a rapid intravenous ‘push’ during
at incision and skin closure. Two studies of 2 g doses in obese preincision time-out, on average 12 min before surgical incision.33
patients were associated with mean or median tissue cefazolin A recent study by Swank et al.34 found only 20% of women with a
concentration close to 4 μg g − 1, and well under the 8 μg g − 1 BMI of 30 to 40 kg m −2, and none of the cohort with a BMI of
recommended therapeutic MIC. Many obese patients receiving 2 g 440 kg m−2 reached an MIC of ⩾ 8 μg ml− 1 after 2 g of cefazolin
of cefazolin will have tissue levels less than the MIC for several of was given 30 to 60 min before cesarean delivery incision. In
the targeted bacteria. A study by Pevzner et al.32 recruited 29 contrast, all women with a BMI of 30 to 40 kg m −2 and 71% of the
women (19 classed as obese with BMI 430 kg m −2) who received women with a BMI of 440 kg m−2 reached target MIC values after
cefazolin 2 g intravenously 30 to 60 min before surgery.32 They receiving 3 g. These findings were challenged by two recent
reported five obese patients with tissue cefazolin concentrations randomized controlled trials investigating adipose tissue cefazolin
below MIC for therapy against Gram-negative rods at the time of concentration in obese women receiving 2 vs 3 g cefazolin.
skin incision, six obese patients with levels below MIC at the time Maggio et al.35 found a similar proportion of women with adipose
of skin closure and two morbidly obese patients (BMI 440 kg m−2) tissue concentrations above 8 μg g− 1 in women receiving 2 vs 3 g
that were subsequently diagnosed with an SSI.32 In contrast, cefazolin within 60 min before skin incision (61% vs 73%, P = 0.35).
Stitely et al.33 identified no patients with tissue cefazolin The fact that a large proportion of women did not attain MIC in
concentrations below MIC at the time of skin incision in their either group is significant. The exact timing of cefazolin dose for
study of 20 obese (BMI 435 kg m− 2) parturients, receiving either 2 both groups was not reported. Young et al.31 found higher plasma
or 4 g cefazolin for cesarean delivery. and adipose tissue concentrations of cefazolin in obese women

Journal of Perinatology (2017), 16 – 20 © 2017 Nature America, Inc., part of Springer Nature.

given 3 vs 2 g within 30 min before incision. The investigators
concluded that both groups attained tissue concentrations above
an MIC of 4 μg g − 1 across all time points. Before fascial entry,
adipose tissue concentration in women given 2 g cefazolin was
o8 μg g − 1 (7.4 vs 12.0 μg g − 1 in women given 3 g, P = 0.18).
A large observational study examining SSI rates in morbidly
obese women undergoing cesarean delivery found no difference
in SSI outcome in women receiving 2 vs 3 g cefazolin.36 However,
the study included laboring women as well as those undergoing
elective cesarean delivery, and was not adequately powered to
assess the effect of 2 vs 3 g dosing on wound infection vs
endometritis separately. Risk of SSI was associated with labor,
duration of rupture of membranes, estimated blood loss
41500 ml and staple wound closure.36
Given the unclear effect of larger cefazolin dosing on wound
infection rates in obese parturients and the inconsistent results of
pharmacokinetic studies, it is clear that further work specifically
examining the effect of timing and dose of anti-microbial
prophylaxis in obese parturients is needed. However, taken
together, the available pharmacokinetic evidence suggests that
cefazolin doses 42 g (i.e., 3 g) administered close to time of
incision may be necessary to ensure that concentrations in
maternal tissues remain above MIC of 8 μg g − 1 in obese pregnant
patients.33 While further study is needed, the current data show an
absence of neonatal toxicity when cefazolin doses up to 4 g are
given in this population.33
CONCLUSION
ACOG guidelines are not consistent with the current pregnancy-
related pharmacokinetic data regarding anti-microbial dosing
for cesarean delivery SSI prophylaxis. Based on available
pharmacokinetic evidence in pregnancy, current ACOG dosing
recommendations for cefazolin administration may lead to drug
levels below therapeutically effective parameters in many
pregnant patients undergoing cesarean delivery. Outcome studies
in pregnant women regarding the optimal dose and timing of
antibiotics for cesarean delivery are still required to provide clear
evidence and guidelines for anti-microbial prophylaxis. However,
while further studies showing the pharmacodynamics and SSI
outcomes of cefazolin in the obstetric population are needed,
current pharmacokinetic evidence demonstrates the importance
of accounting for physiologic changes of pregnancy in women
undergoing cesarean delivery. These drug concentration studies
demonstrate that simply extrapolating study results and guide-
lines from general surgical to obstetric populations may be
misguided. Evidence suggests that in the absence of contra-
indications, the routine initial dose of cefazolin for cesarean
delivery should be at least 2 g to compensate for the effects of
physiological changes of pregnancy on drug pharmacokinetics.
Cefazolin doses 42 g (i.e., 3 g) may be necessary in morbidly
obese women (BMI 440 kg m −2 or 100 kg) undergoing cesarean
delivery. Additionally, based on available pharmacokinetic studies
in pregnancy, and extrapolating from outcome studies on non-
cesarean delivery surgery, narrowing the dose to incision time
interval closer to the time of incision (i.e., 1 to 30 min) in pregnant
women undergoing cesarean delivery may be preferable to
increase therapeutic levels at the time of surgery and thereby
decrease the risk of SSI. This may be particularly important in
obese parturients in whom antibiotic levels may decrease more
rapidly. Data in the pregnant population suggest that modifying
the redosing interval to 3 h, rather than 4 h recommended in the
non-pregnant population, may also be preferable to ensure that
antibiotic levels remain above MIC throughout prolonged
cesarean delivery surgeries.16
© 2017 Nature America, Inc., part of Springer Nature.
Cefazolin prophylaxis for cesarean delivery
AT Duffield et al
19
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ACKNOWLEDGEMENTS
Dr. Sultan has received research capability funding from the National Institute of
Health Research (award reference RCF146/PS/2014). Dr Carvalho received support
from the Arline and Pete Harman Children’s Health Research Institute fund at Lucile
Packard Children’s Hospital at Stanford.
REFERENCES
1 Gibbs RS. Clinical risk factors for puerperal infection. Obstet Gynecol 1980;
55(5, Suppl): 178S–184SS.
2 Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C,
Heuton KR et al. Global, regional, and national levels and causes of maternal
mortality during 1990-2013: a systematic analysis for the Global Burden of Disease
Study 2013. Lancet 2014; 384: 980–1004.
3 Tita AT, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW. Emerging
concepts in antibiotic prophylaxis for cesarean delivery: a systematic review.
Obstet Gynecol 2009; 113(3): 675–682.
4 Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for
preventing infection after cesarean section. Cochrane Database Syst Rev 2014; 10:
CD007482.
5 Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory
statement from the National Surgical Infection Prevention Project. Clin Infect Dis
2004; 38(12): 1706–1715.
6 Bratzler DW, Hunt DR. The surgical infection prevention and surgical care
improvement projects: national initiatives to improve outcomes for patients
having surgery. Clin Infect Dis 2006; 43(3): 322–330.
7 Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK et al.
Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health
Syst Pharm 2013; 70(3): 195–283.
8 ACOG Practice Bulletin No. 120. Use of prophylactic antibiotics in labor and
delivery. Obstet Gynecol 2011; 117(6): 1472–1483.
9 American College of Obstetricians and Gynecologists Committee Opinion No.
465. Antimicrobial prophylaxis for cesarean delivery: timing of administration.
Obstet Gynecol 2010; 116(3): 791–792.
10 Baaqeel H, Baaqeel R. Timing of administration of prophylactic antibiotics for
caesarean section: a systematic review and meta-analysis. BJOG 2013; 120(6):
661–669.
11 Allegaert K, van Mieghem T, Verbesselt R, de Hoon J, Rayyan M, Devlieger R et al.
Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during
pregnancy. Am J Obstet Gynecol 2009; 200(2): 170 e1–170 e7.
12 Anderson GD. Pregnancy-induced changes in pharmacokinetics: a mechanistic-
based approach. Clin Pharmacokinet 2005; 44(10): 989–1008.
13 Smits A, Roberts JA, Vella-Brincat JW, Allegaert K. Cefazolin plasma protein
binding in different human populations: more than cefazolin-albumin interaction.
Int J Antimicrob Agents 2014; 43(2): 199–200.
14 Popovic J, Grujic Z, Sabo A. Influence of pregnancy on ceftriaxone, cefazolin and
gentamicin pharmacokinetics in caesarean vs non-pregnant sectioned women.
J Clin Pharm Ther 2007; 32(6): 595–602.
15 Philipson A, Stiernstedt G, Ehrnebo M. Comparison of the pharmacokinetics of
cephradine and cefazolin in pregnant and non-pregnant women. Clin Pharma-
cokinet 1987; 12(2): 136–144.
16 Elkomy MH, Sultan P, Drover DR, Epshtein E, Galinkin JL, Carvalho B. Pharmaco-
kinetics of prophylactic cefazolin in parturients undergoing cesarean delivery.
Antimicrob Agents Chemother 2014; 58(6): 3504–3513.
17 Heikkila A, Erkkola R. Review of beta-lactam antibiotics in pregnancy. The need for
adjustment of dosage schedules. Clin Pharmacokinet 1994; 27(1): 49–62.
18 Fiore Mitchell T, Pearlman MD, Chapman RL, Bhatt-Mehta V, Faix RG. Maternal and
transplacental pharmacokinetics of cefazolin. Obstet Gynecol 2001; 98(6):
1075–1079.
19 Grujic Z, Popovic J, Bogavac M, Grujic I. Preoperative administration of
cephalosporins for elective caesarean delivery. Srpski arhiv za celokupno lekarstvo
2010; 138(9–10): 600–603.
20 Alexander JW, Solomkin JS, Edwards MJ. Updated recommendations for control of
surgical site infections. Ann Surg 2011; 253(6): 1082–1093.
21 van Kasteren ME, Mannien J, Ott A, Kullberg BJ, de Boer AS, Gyssens IC. Antibiotic
prophylaxis and the risk of surgical site infections following total hip arthroplasty:
timely administration is the most important factor. Clin Infect Dis 2007; 44(7):
921–927.
Journal of Perinatology (2017), 16 – 20
 Cefazolin prophylaxis for cesarean delivery
AT Duffield et al
20
22 Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ et al. Timing of
antimicrobial prophylaxis and the risk of surgical site infections: results from the
Trial to Reduce Antimicrobial Prophylaxis Errors. Ann Surg 2009; 250(1): 10–16.
23 Hawn MT, Richman JS, Vick CC, Deierhoi RJ, Graham LA, Henderson WG et al.
Timing of surgical antibiotic prophylaxis and the risk of surgical site infection.
JAMA Surg 2013; 148(7): 649–657.
24 Weber WP, Marti WR, Zwahlen M, Misteli H, Rosenthal R, Reck S et al. The timing of
surgical antimicrobial prophylaxis. Ann Surg 2008; 247(6): 918–926.
25 Polk HC Jr, Trachtenberg L, Finn MP. Antibiotic activity in surgical
incisions. The basis of prophylaxis in selected operations. JAMA 1980; 244(12):
1353–1354.
26 DiPiro JT, Vallner JJ, Bowden TA Jr, Clark BA, Sisley JF. Intraoperative serum and
tissue activity of cefazolin and cefoxitin. Arch Surg 1985; 120(7): 829–832.
27 Kusaba T. Safety and efficacy of cefazolin sodium in the management of bacterial
infection and in surgical prophylaxis. Clin Med Ther 2009; 1: 1607–1615.
28 Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the
distribution of body mass index among US adults, 1999–2010. JAMA 2012; 307(5):
491–497.
29 Robinson HE, O'Connell CM, Joseph KS, McLeod NL. Maternal outcomes in
pregnancies complicated by obesity. Obstet Gynecol 2005; 106(6): 1357–1364.
30 Schneid-Kofman N, Sheiner E, Levy A, Holcberg G. Risk factors for wound infection
following cesarean deliveries. Int J Gynaecol Obstet 2005; 90(1): 10–15.
Journal of Perinatology (2017), 16 – 20
31 Young OM, Shaik IH, Twedt R, Binstock A, Althouse AD, Venkataramanan R et al.
Pharmacokinetics of cefazolin prophylaxis in obese gravidae at time of cesarean
delivery. Am J Obstet Gynecol 2015; 213(4): 541 e1–541 e7.
32 Pevzner L, Swank M, Krepel C, Wing DA, Chan K, Edmiston CE Jr. Effects of
maternal obesity on tissue concentrations of prophylactic cefazolin during
cesarean delivery. Obstet Gynecol 2011; 117(4): 877–882.
33 Stitely M, Sweet M, Slain D, Alons L, Holls W, Hochberg C et al. Plasma and
tissue cefazolin concentrations in obese patients undergoing cesarean delivery
and receiving differing pre-operative doses of drug. Surg Infect 2013; 14(5):
455–459.
34 Swank ML, Wing DA, Nicolau DP, McNulty JA. Increased 3-gram cefazolin dosing
for cesarean delivery prophylaxis in obese women. Am J Obstet Gynecol 2015; 213
(3): 415.e1–8.
35 Maggio L, Nicolau DP, DaCosta M, Rouse DJ, Hughes BL. Cefazolin prophylaxis in
obese women undergoing cesarean delivery: a randomized controlled trial. Obstet
Gynecol 2015; 125(5): 1205–1210.
36 Ahmadzia HK, Patel EM, Joshi D, Liao C, Witter F, Heine RP et al. Obstetric surgical
site infections: 2 grams compared with 3 grams of cefazolin in morbidly
obese women. Obstet Gynecol 2015; 126(4): 708–715.
37 van Hasselt JG, Allegaert K, van Calsteren K, Beijnen JH, Schellens JH, Huitema AD.
Semiphysiological versus empirical modelling of the population pharmacokinetics
of free and total cefazolin during pregnancy. BioMed Res Int 2014; 2014: 897216.
© 2017 Nature America, Inc., part of Springer Nature.