Increased Cefazolin During Cesarean Delivery in Obese Population
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether an increased prophylactic dose (3 grams) of cefazolin at the time of cesarean delivery has superior coverage in adipose tissue than the current established dosing of 2 grams. The tissue and serum concentration values, when using an increased prophylactic dose, can then be compared to our pilot study assays in hopes of determining an optimal dosing for the obese and morbidly obese populations undergoing cesarean delivery.
A previous study performed at University of California, Irvine (UCI) and Long Beach Memorial Medical Center/Miller Children's Hospital (LBMMC) showed that the standard dose of antibiotics (2 grams of cefazolin) did not provide adequate coverage for all organisms in the obese and extremely obese populations. The purpose of this research study is to evaluate whether in increased dose of antibiotics given before cesarean delivery (3 grams of cefazolin) will reach adequate levels in adipose (fat cells underneath the skin) and serum (blood) samples. In addition, researchers hope to evaluate if/how the mother's weight has an effect on the levels of antibiotics in the tissues (a group of similar cells).
This follow up study (prior study HS# 2009-7015 at UCI) will enroll obese (Body Mass Index (BMI) of 30-40) and morbidly obese (BMI >40) women to receive an increased dose of prophylactic cefazolin at time of scheduled cesarean delivery at both UCI and LBMMC. Researchers hope to enroll a total of 35 women overall.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Study Design:
This is a follow-up to the original pilot study (HS# 2009-7015 at UCI/587-08 at LBMMC). This study is also designed to be a prospective, non-randomized, non-blinded trial of the effects of obesity on adequacy of antimicrobial (cefazolin) concentrations with increased doses (from 2 grams to 3 grams) of preoperative prophylactic antibiotics within adipose tissues at the time of cesarean delivery.
Inclusion Criteria:
• Patients at term (>37 weeks) undergoing a cesarean delivery at LBMMC and UCI.
Exclusion criteria:
-
pre-gestational diabetes
-
chronic hypertension
-
collagen vascular disease
-
renal impairment
-
multiple gestation
-
contraindications to cefazolin administration (known anaphylactic reaction to penicillin's or known cephalosporin allergy)
-
any exposure to cephalosporins in one week prior to cesarean section
-
need for emergent cesarean delivery or diagnosis of chorioamnionitis
Study Procedure:
All patients requiring cesarean delivery under non-emergent circumstances, as determined by their physician, will be approached for participation in study by co-investigators. They will be approached on Labor and Delivery during their intake evaluation on the day of their scheduled procedure. Based on published literature and preliminary power analysis we expect that each of the 2 study groups will need 1414 subjects to demonstrate statistically significant difference in antibiotic concentrations within adipose tissue. The two groups will consist of:
-
OBESE GROUP (BMI 30-40)
-
MORBIDLY OBESE GROUP (BMI >40)
-
All subjects will receive cefazolin at least 30, but no more than 60 minutes prior to skin incision.
-
At the time of cesarean delivery, the following tissue samples will be collected:
-
adipose tissue immediately following skin incision (prior to incision of the fascia) and
-
adipose tissue prior to skin closure
-
serum sample after skin incision but prior to completion of the operative procedure
Approximately 2 grams of tissue sampled from each site and 5 cc of blood will be required for analysis.
All samples will be collected by Dr. Swank, Dr. Wing or a physician who had previously been proctored in the proper tissue collecting techniques by either of the above mentioned investigators. Upon collection, tissue specimens will be blotted to remove residual blood and debris, weighed, and placed in a freezer (-80'C) until analysis. Serum samples will be drawn into red top tubes and immediately placed on wet ice. Immediately following completion of the surgery, they will then be centrifuged for 10 minutes at 3G (3200 rpm) and placed in a locked -80'C freezer until analysis.
Tissue and serum samples will then be sent to David P. Nicolau, PhD, FCCP, FIDSA, at the Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut. Samples will be batched and sent all together at the completion of study enrollment. Dr. Swank and the study nurse will be responsible for securely packing samples on dry ice and overnight shipping them to Dr. Nicolau. Once with Dr. Nicolau, the tissue samples will be homogenized and analyzed to determine zones of inhibition. The Cefazolin concentrations will be determined in the serum samples using a previously validated high-performance liquid chromatography method. 16 Tissues and serum will be sent without direct identifiers. Dr. Nicolau will not have access to the identity of the research subjects providing the samples.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cefazolin All subjects undergoing elective term cesarean delivery will receive 3 grams of Cefazolin at least 30, but no more than 60 minutes prior to skin incision. |
Drug: Cefazolin
Participants who are undergoing an elective cesarean section at term will receive 3 grams of Cefazolin at least 30, but no more than 60 minutes prior to skin incision administered through an intravenous line.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Achievement of Minimal Inhibitory Concentrations Within Adipose and Serum Sampled at Time of Cesarean Delivery [Each participant is to be observed per routine operative and post-operative guidelines, inpatient for 3-4 days.]
Primary Objective: To assess the effects of increased prophylactic doses of Cefazolin in the obese and morbidly obese populations undergoing cesarean delivery. Effects will be defined as the ability to reach the minimal inhibitory concentrations for gram-positive and gram-negative organisms in adipose tissue and serum at time of skin incision and skin closure as defined by the Clinical and Laboratory Standards Institute
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients at term (>37 weeks) undergoing a cesarean delivery at Women's Pavilion at Miller Children's Hospital and University of California, Irvine.
Exclusion Criteria:
-
pre-gestational diabetes
-
chronic hypertension
-
collagen vascular disease
-
renal impairment
-
multiple gestation
-
contraindications to Cefazolin administration (known anaphylactic reaction to penicillin's or known cephalosporin allergy)
-
any exposure to cephalosporins in one week prior to cesarean section
-
need for emergent cesarean delivery or diagnosis of chorioamnionitis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | MemorialCare Center for Women at Miller Children's Hospital Long Beach and Long Beach Memorial Medical Center | Long Beach | California | United States | 90806 |
| 2 | University of California, Irvine | Orange | California | United States | 92868 |
Sponsors and Collaborators
- MemorialCare Health System
- University of California, Irvine
Investigators
- Principal Investigator: Jennifer McNulty, MD, MemorialCare Center for Women at Miller Children's Hospital Long Beach and Long Beach Memorial Medical Center
- Principal Investigator: Deborah A Wing, MD, University of California, Irvine
- Principal Investigator: Morgan Swank, MD, University of California, Irvine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 186-13
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 3g Cefazolin |
|---|---|
| Arm/Group Description | Prospective cohort obese women receiving 3g prophylactic cefazolin 30-60 minutes prior to scheduled cesarean delivery |
| Period Title: Overall Study | |
| STARTED | 30 |
| Obese (BMI 30-40kg/m^2) | 14 |
| Extremely Obese (BMI >40kg/m^2) | 14 |
| COMPLETED | 28 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | 3g Cefazolin |
|---|---|
| Arm/Group Description | 3g IV cefazolin given 30-60 minutes prior to skin incision |
| Overall Participants | 28 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
28
100%
|
| >=65 years |
0
0%
|
| Age (years) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [years] |
31.5
|
| Sex: Female, Male (Count of Participants) | |
| Female |
28
100%
|
| Male |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
2
7.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
10.7%
|
| White |
5
17.9%
|
| More than one race |
18
64.3%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (Count of Participants) | |
| United States |
28
100%
|
| preoperative hemoglobin (g/dL) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [g/dL] |
12.0
|
| Average BMI (kg/m2) [Mean (Standard Deviation) ] | |
| Obese, BMI 30-40kg/m^2 |
33.82
(2.92)
|
| Extremely Obese, BMI >40kg/m^2 |
45.03
(3.77)
|
Outcome Measures
| Title | Achievement of Minimal Inhibitory Concentrations Within Adipose and Serum Sampled at Time of Cesarean Delivery |
|---|---|
| Description | Primary Objective: To assess the effects of increased prophylactic doses of Cefazolin in the obese and morbidly obese populations undergoing cesarean delivery. Effects will be defined as the ability to reach the minimal inhibitory concentrations for gram-positive and gram-negative organisms in adipose tissue and serum at time of skin incision and skin closure as defined by the Clinical and Laboratory Standards Institute |
| Time Frame | Each participant is to be observed per routine operative and post-operative guidelines, inpatient for 3-4 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| participants were divided in BMI categories, 30-40kg/m2 and >40kg/m2. |
| Arm/Group Title | 3g Cefazolin |
|---|---|
| Arm/Group Description | Prospective cohort obese women receiving 3g prophylactic cefazolin 30-60 minutes prior to scheduled cesarean delivery |
| Measure Participants | 28 |
| BMI 30-40 3g |
22.4
|
| BMI >40 3g |
9.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3g Cefazolin |
|---|---|---|
| Comments | To detect the number of subjects who obtained a minimal inhibitory concentration (>4mg/ml) following increased 3g dose of cefazolin. Compare this number to the historical cohort who had received 2g of cefazolin (standard dosing) | |
| Type of Statistical Test | Other | |
| Comments | we used t-test on the regression coefficient for the group indicator to test for differences in means categorical variables were evaluated using fisher's exact test of association linear regression for log transformed start adipose concentrations were calculated by dose specific group | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 80 | |
| Confidence Interval |
(2-Sided) 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | 3g Cefazolin | |
| Arm/Group Description | 3g cefazolin provided via IV push 30-60 minutes prior to skin incision | |
All Cause Mortality |
||
| 3g Cefazolin | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| 3g Cefazolin | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| 3g Cefazolin | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Morgan Swank |
|---|---|
| Organization | Memorial Care |
| Phone | 5624808460 |
| morganswankmd@gmail.com |
- 186-13