Clinical trial NCT00980486: Obesity and Antibiotic Tissue Concentration
Official title: Effects of Maternal Obesity on Tissue Concentrations of Prophylactic Antibiotics During Cesarean Delivery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: Antibiotic Concentration
Tissue
Obesity
Cesarean
Lead sponsor: MemorialCare
Sponsor class: OTHER
Collaborators: name: University of California, Irvine
First posted: 2009-09-21
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients requiring cesarean delivery under non-emergent circumstances

Brief summary: The purpose of this study is to determine whether the dose of prophylactic antibiotics at the time of cesarean delivery requires adjustment in obese and overweight patients in order to achieve optimal antimicrobial activity.

Detailed description: The majority of information regarding pharmacokinetics and pharmacodynamics (the action, properties and elimination of a drug in the body) of antibiotics is based on measurements of the serum and plasma concentrations. Current guidelines for surgical antibiotic prophylaxis have clearly demonstrated appropriate therapeutic levels within blood and serum levels, resulting in low incidence of postoperative bacteremia (bacteria in the blood) and sepsis (infection). Despite this, surgical site infections (SSI) remain the most common postoperative complication, affecting up to 20% of patients undergoing intra-abdominal surgery. Inadequate antibiotic penetration into the tissues of the surgical site, in spite of therapeutic serum levels, results in an environment that is susceptible to pathogens and subsequent infections. Antimicrobial tissue levels are influenced by volume of distribution, regional blood flow and biological properties of tissue. The ability of any drug to reach the tissue of interest is dictated by the relative amount of blood flow to that organ. While lungs and kidneys enjoy a robust blood supply, subcutaneous adipose tissue (fat) (the most frequent site of surgical site infections) receives a small fraction of the cardiac output. Obesity creates an increased volume of distribution, thereby resulting in a greater dilution of antibiotics when compared to non-obese subjects. Moreover, this change in volume of distribution is achieved primarily by increasing the relative amount of poorly perfused adipose tissue. Therefore, it should come as no surprise that obesity is a significant risk factor for surgical site infections.

The rate of obesity in the United States has shown a steady increase and more than doubled in the last twenty-five years from 15% in 1980 to 32.9% in 2004. Moreover, nearly one third of women of reproductive age are obese and approximately 6% are extremely obese. In addition to the usual health related concerns, obesity significantly increases the rate of complications associated with pregnancy. In particular, several studies have demonstrated an increased incidence of cesarean delivery associated to maternal obesity. Cesarean delivery rates, much like obesity rates, have witnessed a tremendous surge in the last few decades and now account for approximately 30% of all deliveries or nearly 1.2 million procedures. Surgical site infections associated with cesarean delivery include wound infections and endomyometritis (infection in the uterus), with rates ranging from 7% to 20% depending on the demographic and obstetric variables. Despite these alarming trends there is a paucity of data regarding antimicrobial activity of prophylactic antibiotics in tissues and the effects of maternal obesity on these concentrations at the time of cesarean delivery.

While the rates of cesarean deliveries have reached a plateau at around 30% in recent years, the rates of obesity continue to climb unabated. As the attributes of the population evolve over the course of time so must the guidelines and management adapt to the individuals in our care.

Eligibility criteria: Inclusion Criteria:

* Patients at term (\> 37 weeks) undergoing a cesarean delivery.

Exclusion Criteria:

* Women younger than 18 years,
* Pre-gestational diabetes,
* Chronic hypertension,
* Collagen vascular disease,
* Multiple gestation,
* Contraindications to cefazolin administration (known anaphylactic reaction to penicillins or known cephalosporin allergy),
* Any exposure to cephalosporins in one week prior to cesarean section, OR
* Need for emergent cesarean delivery or diagnosis of chorioamnionitis.

Primary outcomes:
measure: To assess the effects of maternal obesity on the concentrations and adequacy of antimicrobial activity of prophylactically administered antibiotics within tissues (subcutaneous adipose and myometrial) at the time of cesarean delivery.
timeFrame: 6 weeks
Secondary outcomes:
measure: To assess the concentrations and adequacy of antimicrobial activity of prophylactically administered antibiotics within tissues (subcutaneous adipose and myometrial) at the time of cesarean delivery.
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Women's Pavilion at Miller Children's Hospital
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
Study officials:
affiliation: Long Beach Memorial Medical Center
name: Kenneth Chan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Apr;117(4):877-882. doi: 10.1097/AOG.0b013e31820b95e4.