Lowering the Risk for Surgical Site Infections in Fat Folk

Image from Chopra 2010 study, link below

We've discussed prevention of surgical site infections before, often in the context of cesareans, but most recently in the context of Emergency Room visits.

Regardless of type of operation, however, accumulating evidence suggests that antibiotic regimens for "obese" people need to be adjusted.

We in the Size Acceptance Movement have been saying for years that people of size often benefit from larger or weight-based dosing for certain types of antibiotics, longer courses of antibiotics in some cases, and IV antibiotics instead of oral antibiotics for serious infections.

This was based on the anecdotal experiences of many people of size over the years, and as such, was summarily dismissed by many in the medical community.

Here is research that confirms the importance of longer courses of antibiotics and weight-based dosing, and which also suggests that more frequent dosing, administration of antibiotics by IV, and perhaps topical infusion of antibiotics into the wound  itself before closing (instead of just systemically in the IV) seem to improve outcomes.

Of course, different types of antibiotics work differently in the system. This means that some types of antibiotics need different dosing for obese people and some don't.  That's important to remember ─ the need for weight-based dosing is not universal for all drugs.  And to be fair to doctors, research has been slow to differentiate these and to provide easy-to-use guidance to doctors in their prescriptions.

Yet there is some research that addresses this issue now, but as we saw recently in the Emergency Room study, getting doctors to follow this research is difficult. In that study, simple guidelines for dosing for high-BMI patients in the E.R. were readily available, but even so, less than 5% of morbidly obese patients received the proper initial dosage of common antibiotics. And that was at a medical center that specialized in treating obese patients!

Furthermore, another study has shown that hospital pharmacists often do not catch/correct underdosing errors in high-BMI patients.  In that study, less than 1/3 of obese patients received an adequate initial dose of vancomycin, only 1% received the optimum recommended dose, and only about 3% of these underdosing cases were caught and corrected by hospital pharmacists.

Far too often, people of size are still being treated with standard antibiotic dosages instead of dosages tailored to their weight, or antibiotics given too infrequently, orally, or for an insufficient length of time.

When will doctors listen to people of size and learn from our experiences?  Heck, when will they learn from their own research?

What is the barrier to adopting these new regimens?  Why aren't they being utilized far more often?  Why aren't hospital pharmacists or medical supervisors catching more inadequate dosing and raising red flags about it?

It's frustrating that this topic is only now being researched and that many hospitals ─ even those that specialize in treating obese patients ─ have been slow to utilize the new dosing guidelines that do exist.

As people of size, we need to be our own best advocates, both before surgery and when surgical site infections occur, so don't be afraid to bring up this concern with your surgeon, or to ask for a consult with an infectious specialist.  Even with a specialist, you may have to be ready to assertively argue your case, but they are more likely to be responsive to advocacy if you can cite research like the studies below.

Providers, please press hard for more research on the most optimal antibiotic dose and regimens, and press vigorously for more caregiver education about and usage of these regimens.  If there is any question about optimal dosage, please take the time to research the issue, and don't be afraid to explore using a different timing or delivery system.  It could literally be the difference between life and death for some people of size.

Infections can be a significant problem in high-BMI patients. Part of this is because of physiological differences like decreased vascular perfusion in fat tissue, and thus decreased oxygenation.  But an under-recognized part of it is because clinicians are using the wrong dosages and treatment regimens for fat folk.

The most efficient approach to improving outcome in obese patients is still to prevent infection in the first place by using the most effective antibiotic dose and treatment protocols available for our unique needs.


References

Am J Obstet Gynecol. 2010 Mar;202(3):306.e1-9. Extended antibiotic prophylaxis for prevention of surgical-site infections in morbidly obese women who undergo combined hysterectomy and medically indicated panniculectomy: a cohort study. El-Nashar SA, et al.   PMID: 20207249

OBJECTIVE: The purpose of this study was to compare surgical-site infection rates in obese women who had extended prophylactic antibiotic (EPA) vs standard prophylactic antibiotic.
STUDY DESIGN: An electronic records-linkage system identified 145 obese women (body mass index, >30 kg/m(2)) who underwent combined hysterectomy and panniculectomy from January 1, 2005, through December 31, 2008. The EPA cohort received standard antibiotics (cefazolin, 2 g) and continued oral antibiotic (ciprofloxacin) until removal of drains. Regression models were used to adjust for known confounders. RESULTS:The mean age was 56.0 + or - 12.1 years, and mean body mass index was 42.6 + or - 8.4 kg/m(2) (range, 30-86.4 kg/m(2)). The EPA cohort experienced fewer surgical-site infections (6 [5.9%] vs 12 [27.9%]; P less than .001; adjusted odds ratio, 0.16; 95% confidence interval, 0.04-0.51; P less than .001), had lower probability of incision and drainage (3 [2.9%] vs 5 [11.6%]; P = .05), and required fewer infection-related admissions (5 [4.9%] vs 6 [13.9%]; P = .08). CONCLUSION: Extended antibiotic prophylaxis can reduce surgical-site infections in obese women after combined hysterectomy and panniculectomy.

Surg Infect (Larchmt). 2009 Feb;10(1):53-7. Prevention of surgical site infections by an infusion of topical antibiotics in morbidly obese patients. Alexander JW, Rahn R, Goodman HR.  PMID: 19245364 

BACKGROUND: The reported incidence of surgical site infection after abdominal surgery in morbidly obese patients is high (about 15% in most studies), and this is associated with considerable disability and an increased economic burden. Topical antibiotics may reduce the incidence of serious infections. METHODS: Standard techniques for the prevention of surgical site infections were used along with the introduction of kanamycin into the subcutaneous space of morbidly obese patients at the time of closure and allowing it to dwell for 2 h. Eight hundred thirty-seven evaluable patients were followed for the development of site complications for at least six weeks postoperatively. RESULTS: One of the 65 patients with a revisional procedure had a primary deep incisional surgical site infection, as did one of the 772 patients with a primary operation. Secondary deep incisional surgical site infections occurred in four patients, two after spontaneous evacuation of a seroma, one from excessive superficial contamination, and one following separation of a nonhealing surgical site. Additionally, 21 patients had minor surgical site complications including incisional separation and stitch-related infections, which required no significant expenditure of resources. CONCLUSIONS: Prolonged contact (2 h) of topical kanamycin solution with the surgical site greatly reduces the incidence of primary infections in the deep subcutaneous space of laparotomy sites in morbidly obese patients.

Expert Rev Pharmacoecon Outcomes Res. 2010 Jun;10(3):317-28. Preventing surgical site infections after bariatric surgery: value of perioperative antibiotic regimens. Chopra T, et al.   PMID: 20545596    Full free text available here.

Kmom Summary: This paper reviews the surgical site infections (SSIs) that occur post bariatric surgery, and how to prevent SSIs. "This paper sets out to define different types of SSIs that occur following bariatric surgery and to discuss existing literature on the critical aspects of SSI prevention and the appropriate use of surgical antimicrobial prophylaxis for bariatric surgery."   

Important quote: "Most antimicrobial agents do not achieve optimal serum levels when administered orally. Although certain oral antimicrobials have comparable bioavailability with their intravenous formulation, the time to achieve maximum serum concentration is slower due to the need for absorption through the gastrointestinal tract. Intravenous antimicrobial prophylaxis is the most extensively studied route and remains the preferred route of administration."

Obes Surg. 2012 Mar;22(3):465-71. Cefepime dosing in the morbidly obese patient population. Rich BS, et al.  PMID: 22249886

Proper dosing of specific antibiotics in morbidly obese patients has been studied inadequately. However, these data are beneficial as this patient population is at an increased risk to develop postoperative infections. Cefepime is an antibiotic used for the treatment of both gram-positive and especially gram-negative infections; administration of the appropriate dose in the morbidly obese population is crucial. We therefore examined the pharmacokinetics of cefepime in patients with body mass index >40 kg/m(2). Ten morbidly obese patients, with a mean [±SD] estimated glomerular filtration rate of 108.4 ± 34.6 mL/min, undergoing elective weight loss surgical procedures were administered cefepime in addition to standard prophylactic cefazolin and studied. Serial serum cefepime concentrations were analyzed after dosing using a validated high performance liquid chromatography method. Pharmacokinetics and duration above the minimum inhibitory concentration (MIC) were determined using a protein binding value of 15% and a MIC threshold of 8 μg/mL. Mean free cefepime concentrations for t = 30, 120, and 360 min were 69.6, 31.6, and 9.2 μg/mL, respectively. The dosing interval was calculated to maintain the free concentration above the MIC (fT > MIC) for 60% of the interval. This was determined to be 10.12 h, including time for infusion. There was no toxicity. Based on this analysis, an increased dose of 2 g every 8 h is necessary to maintain an adequate fT > MIC throughout the dosing interval. Further studies are necessary to determine the efficacy of this regimen in the settings of active infections and critical illness.

Pharmacotherapy. 2007 Aug;27(8):1081-91.  Antimicrobial dosing considerations in obese adult patients. Pai MP, Bearden DT.    PMID: 17655508

As obesity continues to increase in prevalence throughout the world, it becomes important to explore the effects that obesity has on antimicrobial disposition. Physiologic changes in obesity can alter both the volume of distribution and clearance of many commonly used antimicrobials. These changes often present challenges such as estimation of creatinine clearance to predict drug clearance.

Although these physiologic changes are increasingly being characterized, few studies assessing alterations in tissue drug distribution and the effects of obesity on antimicrobial pharmacokinetics have been published. The available data are most plentiful for antibiotics that historically have included clinical therapeutic drug monitoring.

These data suggest that dosing of vancomycin and aminoglycosides be based on total body weight and adjusted body weight, respectively. Obese patients may require larger doses of beta-lactams to achieve similar concentrations as those of patients who are not obese. Fluoroquinolone pharmacokinetics are variably altered by obesity, which prevents a uniform approach. Data on the pharmacokinetics of drugs that have activity against gram-positive organisms-quinupristin-dalfopristin,linezolid, and daptomycin-reveal that they are altered in the presence of obesity, but more data are needed to solidify dosing recommendations. Limited data are available on nonantibacterials. 

An understanding of the physiologic changes in obesity and the available literature on specific antibiotics is valuable in providing a framework for rational selection of dosages in this increasingly common population of obese patients.

Am J Med. 2008 Jun;121(6):515-8.  Multicenter evaluation of vancomycin dosing: emphasis on obesity. Hall RG 2nd, Payne KD, Bain AM, Rahman AP, Nguyen ST, Eaton SA, Busti AJ, Vu SL, Bedimo R.    PMID: 18501233 Full text available here.

BACKGROUND: There is a paucity of data available regarding the dosing of antimicrobials in obesity. However, data are available demonstrating that vancomycin should be dosed on the basis of actual body weight. METHODS: This study was conducted at 2 tertiary care medical centers that did not have pharmacy-guided vancomycin dosing programs or other institutional vancomycin dosing policies or protocols. Patients who received vancomycin between July 1, 2003, and June 30, 2006, were stratified by body mass index and randomly selected from the computer-generated queries. Patients greater or equal to 18 years of age with a creatinine clearance of at least 60 mL/min who received vancomycin for at least 36 hours were included. RESULTS: Data were collected on a random sampling of 421 patients, stratified by body mass index, who met the inclusion criteria. Most patients in each body mass index category received a fixed dose of vancomycin 2 g daily divided into 2 doses (underweight 82%, normal weight 90%, overweight 86%, and obese 91%).  

Adequate initial dosing (greater than or=10 mg/kg/dose) was achieved for 100% of underweight, 99% of normal weight, 93.9% of overweight, and 27.7% of obese patients (P less than .0001).

Ninety-seven percent of underweight, 46% of normal weight, 1% of overweight, and 0.6% of obese patients received greater than or =15 mg/kg/dose recommended by several Infectious Diseases Society of America guidelines.

Pharmacists also failed to correct inadequate dosing because only 3.3% of patients receiving less than 10 mg/kg/dose had their regimen changed in the first 24 hours of therapy.

CONCLUSION: In this multicenter pilot study, obese patients routinely received inadequate empiric vancomycin using a lenient assessment of dosing. Greater efforts should be undertaken to ensure patients receive weight-based dosing because inadequate dosing can lead to subtherapeutic concentrations and potentially worse clinical outcomes.

Eur J Clin Pharmacol. 1998 Oct;54(8):621-5. Vancomycin dosing in morbidly obese patients. Bauer LA, Black DJ, Lill JS.   PMID: 9860149 

OBJECTIVES AND METHODS: Vancomycin hydrochloride dosing requirements in morbidly obese patients with normal renal function were computed to determine the dose of vancomycin necessary to achieve target steady-state peak and trough concentrations and compared with a normal weight population.  RESULTS: Morbidly obese patients [total body weight (TBW) 165 kg, ideal body weight (IBW) 63 kg] required 31.2 mg x kg(-1) x d(-1) TBW or 81.9 mg x kg(-1) x d(-1) IBW to achieve the target concentrations. Normal weight patients (TBW 68.6 kg) required 27.8 mg x kg(-1) x d(-1) to achieve the same concentrations. Because of altered kinetic parameters in the morbidly obese patients (obese: t1/2 = 3.3 h, V = 52 L, CL = 197 ml x min(-1); normal: t1/2=7.2 h, V=46 L, CL=77 ml x min(-1), 20 of 24 patients required q8h dosing (1938 mg q8h) compared with q12h dosing (954 mg q12h) in all normal weight patients in order to avoid trough concentrations that were too low for prolonged periods. There was a good correlation between TBW and CL, but only fair correlation between TBW and V. CONCLUSION: Doses required to achieve desired vancomycin concentrations are similar in morbidly obese and normal weight patients when TBW is used as a dosing weight for the obese (approximately 30 mg x kg(-1) x d(-1)). Shorter dosage intervals may be needed when dosing morbidly obese patients so that steady-state trough concentrations remain above 5 microg x ml(-1) in this population. Because of the large amount of variation in required doses, vancomycin serum concentrations should be obtained in morbidly obese patients to ensure that adequate doses are being administered. Dosage requirements for morbidly obese patients with renal dysfunction require further study.

Surgery. 2004 Oct;136(4):738-47. Perioperative antibiotic prophylaxis in the gastric bypass patient: do we achieve therapeutic levels? Edmiston CE, et al.    PMID: 15467657

BACKGROUND: Perioperative surgical antibiotic prophylaxis requires that therapeutically effective drug concentrations be present in the tissues. METHODS: Patients undergoing Roux-en-Y gastric bypass for morbid obesity were given 2 g cefazolin preoperatively, followed by a second dose at 3 hours. Thirty-eight patients were each assigned to 1 of 3 body mass index (BMI) groups: (A) BMI=40-49 (N = 17); (B) BMI=50-59 (N=11); (C) BMI > or= 60 (N=10). Multiple timed serum (baseline; incision, 15, 30, 60 minutes; prior to second prophylactic dose; and closure) and tissue (skin, subcutaneous fat, and omentum) specimens were collected and cefazolin concentration analyzed by microbiological assay. RESULTS: No significant difference was observed in intraoperative fluid replacement or blood loss among BMI groups. Serum antimicrobial concentrations exceeded resistance breakpoint (32 microg/mL) in 73%, 68%, and 52% of BMI groups A, B, and C, respectively. No significant difference in cefazolin concentration was observed in mean incisional skin and closure tissue specimens in groups A, B, and C. A significant decrease in cefazolin concentration was noted in closure adipose (p=.04), initial (p=.03) and closure omentum (p=.05) tissues in groups B and C compared with A. Over 90% of serum samples exhibited therapeutic concentrations covering 53.8% of gram-positive and 78.6% of gram-negative surgical pathogens. However, therapeutic tissue levels were achieved in only 48.1%, 28.6%, and 10.2% of groups A, B, and C, respectively. CONCLUSIONS: Pharmacokinetic analysis suggests that present dosing strategies may fail to provide adequate perioperative prophylaxis in gastric bypass patients.

Am J Emerg Med. 2011 Dec 12. Underdosing of common antibiotics for obese patients in the ED. Roe JL, Fuentes JM, Mullins ME.  PMID: 22169576

BACKGROUND: Obesity is a growing problem in the United States. Obesity alters the pharmacokinetic profiles of various drugs. Although there are guidelines for dose adjustments for many of the antibiotics commonly used in the emergency department (ED), they are seldom used. METHODS: This is an institutional review board-approved retrospective study at an American Society of Metabolic and Bariatric Surgery Center of Excellence and a level I trauma center with annual ED volumes of more than 80 000 visits. Data were retrospectively collected from ED pharmacy records during a 3-month period in 2008. Any first dose of cefepime, cefazolin, or ciprofloxacin administered in our ED to a patient recorded as both more than 100 kg and with a body mass index greater than 40 kg/m(2) was compared with our hospital guidelines and found to either adhere or not adhere to those guidelines. RESULTS: There were 1910 orders found to meet the study criteria: 775 orders for cefepime, 625 orders for cefazolin, and 510 orders for ciprofloxacin. Adherence rates for first dose of cefepime, cefazolin, and ciprofloxacin administered, respectively, were 8.0%, 3.0%, and 1.2%. CONCLUSION: Emergency physicians frequently underdose cefepime, cefazolin, and ciprofloxacin in obese patients. Underdosing antimicrobials presents risk of treatment failure and may promote antimicrobial resistance. Education is necessary to improve early antibiotic administration to obese patients.