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Evaluation of Physician Prescribing Patterns For Antibiotics in the Treatment of Nonnecrotizing Skin and Soft Tissue Infections
The increasing incidence of skin and soft tissue infections (SSTIs), with a corresponding rise in hospital admissions, poses a public health dilemma that requires a more tailored clinical pharmacotherapy intervention. Increasing incidence is evident in about 15 million annual cases of SSTIs1 and more than 869,000 annual hospital admissions in the United States.2 This common clinical condition can have mild to life-threatening complications.
Cellulitis is a subtype of SSTI that is among the most frequent in hospitalized patients. Among 471,550 patients with SSTIs hospitalized between 2009 and 2011, cellulitis accounted for 63% (298,036).3 Cellulitis is a serious SSTI due to its acute infectious process and its propensity to spread through lymphatic tissue and the bloodstream.4 In the recent terminology of the Food and Drug Administration’s Center for Drug Evaluation and Research, cellulitis is classified as an acute bacterial skin and skin structure infection (ABSSSI).5
Hospitalized patients with SSTIs tend to have a longer hospital stay than patients without SSTIs. A matched cohort study by Hatoum et al. found that hospitalized patients with SSTIs spent, on average, an additional 3.81 days in the hospital with an increased hospitalization cost of $14,974 compared with patients without SSTIs.6 A prospective, multicenter, observational study by Lipsky et al. found that patients with ABSSSIs had an average hospital stay of 7.1 days.7
Current practices that could contribute to such patient outcomes include paucity of a consensus on optimal pharmacotherapy protocol, prolonged use of broad-spectrum antibiotics, or treatment course. This was highlighted in a multicenter retrospective study by Jenkins et al. in which the use of broad gram-negative antibiotics or a treatment course longer than 10 days were common among hospitalized patients with ABSSSIs.8 Such clinical practices and the lack of a consensus on drug treatment offer the clinical pharmacist a substantial opportunity for a protocol-based pharmacotherapy intervention with a goal of reducing unnecessary antibiotic exposure, improving patient outcomes, and utilizing hospital resources more efficiently.
To generate data for the development of a hospital-based protocol for nonnecrotizing SSTI treatment, this research sought to evaluate physician prescribing patterns and duration for antibiotics in the treatment of these infections. We hypothesized that there is a substantial opportunity for antimicrobial stewardship practice and clinical pharmacist interventions. The study also assessed the impact of the institution’s current antibiotic treatment of nonnecrotizing SSTIs on hospital length of stay, readmission rate, and hospitalization cost.
This study was a single-center, retrospective electronic chart review of patients admitted to the hospital for cellulitis and abscess based on International Classification of Diseases, Ninth Revision (ICD-9) codes of 680–682.9. The presence of cellulitis and abscess was confirmed by the history and physical examination (H&P) description provided by the admitting physician, documentation of the patient H&P, and subsequent progress notes. Similarly, the presence of purulence was documented, together with an incision and drainage procedure as described by the physician in the patient chart. The study was approved by both the Xavier University of Louisiana and Louisiana State University institutional review boards.
This study was done at the University Medical Center New Orleans, a tertiary academic teaching hospital and level 1 trauma center. Patients have access to care at the same location via the emergency department, the 283-bed hospital, and specialty ambulatory clinics. The medical center caters mostly to an indigent and uninsured population.
All patients 18 years of age and older with ICD-9 codes of 680–682.9 for cellulitis and abscesses at the time of admission were eligible for this study. ICD-9 codes were used to determine both admitting and discharge diagnoses. Patients younger than 18 years of age and patients without ICD-9 codes of 680–682.9 were excluded.
The following data were collected from eligible charts: age, gender, race, site of infection, microbiological culture results, length of stay, antibiotics, length of therapy, cost of hospitalization, readmission rates (14 days and 30 days), causative pathogen, primary service at admission, and penicillin allergy.
The following comorbidity data were also collected: diabetes, intravenous (IV) drug use, prior methicillin-resistant Staphylococcus aureus (MRSA) infection, recent surgery (defined as surgery within the last month), prior history of cellulitis, peripheral artery disease, peripheral vascular disease, and diagnosed alcoholism. The cost of hospitalization was determined by documenting the total bill for the specific encounter.
The primary and secondary outcomes were specified before the study began. The primary outcome was the physician adherence rate to the 2014 Infectious Diseases Society of America (IDSA) guideline recommendation on empiric antibiotic selection.8 The secondary outcomes included physicians’ antibiotic selection, duration of treatment, readmission rate (defined as readmission within 30 days after hospital discharge), and cost of hospitalization.
To assess the primary and some secondary outcomes, current physician practice patterns in regard to selection of empiric antibiotics and duration of therapy were compared to the 2014 IDSA clinical guideline recommendations. Physicians’ choices of empiric antibiotics for nonnecrotizing SSTIs were compared to guideline-recommended empiric antibiotics.
Descriptive data analysis was performed for demographic characteristics, chi-square for comparison of categorical data, and logistic regression analysis for impact of independent variables on adherence to guidelines. A P value of less than 0.05 was considered statistically significant. SAS statistical software (version 9.4) was used for the data analysis.
Two hundred and twenty-two patients with ICD-9 codes for cellulitis and abscess admission between August 2014 and August 2015 were screened for eligibility. Fourteen patients were excluded during the screening process because they left against medical advice after admission. In total, 208 patient charts were reviewed for data collection and results analysis (
Baseline Comorbidity and Site of Infection
IV drug use and diabetes were the most common baseline active comorbid conditions at the time of patient admission (
Causative Pathogen and Nonpharmacological Intervention
Among patients for whom a culture was done, 39% had a positive result, and gram-positive microbes were the main causative pathogens. MRSA was the most common isolated pathogen (
There was a 40% adherence rate to the IDSA guideline recommendations on empiric antibiotic selection. Vancomycin was the most frequent empiric antibiotic selected for nonnecrotizing SSTI treatment (
The median duration of therapy was 12 days, with a 70% adherence rate to guideline recommendations (
Both logistic regression and chi-square analysis of the data showed that gender and presence of purulence had a statistically significant effect on guideline adherence rate (
Cellulitis and abscesses are among the most common subtypes of skin and skin structure infections leading to hospitalization. There has been a lack of consensus on optimal pharmacotherapy management, but the IDSA has recently published guidelines for the management of these infections.8 Despite these guidelines, we hypothesized that, in an academic teaching institution such as ours, there would be substantial variation in pharmacotherapy strategies used for nonnecrotizing SSTIs. This study was initiated to assess current antibiotic prescribing practices for nonnecrotizing SSTI management, while generating data to guide the development of a standardized antibiotic selection pathway protocol for their management.
Gram-positive bacteria were the primary causative pathogens for cellulitis as shown by the culture results of our study. S. aureus was the most common isolated pathogen, with MRSA as the most frequent isolate. This outcome is similar to the result of a retrospective epidemiologic study by Ray et al.3 In our study, vancomycin was the most common monotherapy initiated. When combination therapy was used, piperacillin/tazobactam plus vancomycin or clindamycin plus vancomycin were most commonly initiated.
The high use of vancomycin as monotherapy likely reflects heightened concern about community-onset MRSA as the cause for cellulitis. Several studies, including Jenkins et al.,9 have reported that MRSA is the major cause of SSTI. Our study also demonstrated that MRSA was a common pathogen in these infections. Furthermore, a prospective multicenter study by Lipsky and colleagues reported that vancomycin was the most common empiric antibiotic used in the management of complicated skin and soft tissue infections.7
The frequent use of piperacillin/tazobactam and vancomycin as an initial combination pharmacotherapy is likely due to concern for broad coverage as a result of the baseline comorbidities of those admitted for cellulitis management. In our cohort, diabetes was one of the common comorbidities. In these patients, there is a perceived need to cover a broad spectrum of pathogens in cellulitis. The rationale for the combination of clindamycin and vancomycin could stem from the antitoxin properties of clindamycin.10
The upper extremities and lower extremities were the most common sites of infection in our study. This is in contrast to Lipsky et al., who reported the lower foot as the most common site at clinical presentation.7 In our study, IV drug use and diabetes were the most common baseline comorbidities. Most cellulitis related to IV drug use occurs within the upper extremities, while diabetes-related skin infections occur mostly in the lower extremities.
We found a high degree of compliance with the IDSA guideline recommendation of incision and drainage (96.6%), but much lower adherence with recommended empiric antibiotic therapy (40%). The high adherence rate for nonpharmacological management of cellulitis infections likely reflects the widespread understanding about the importance of incision and drainage in abscesses.
The 40% adherence rate to recommended empiric antibiotic therapy seen in our study is also not surprising. The major factor in nonadherence was the frequent use of empiric antibiotic combination therapy when not appropriate. This was associated with evidence of purulence on presentation. Interestingly, male gender was also associated with poorer adherence to guidelines, but overall purulence was higher in men than in women (70% versus 30%).
Purulence as an independent predictor of adherence rate was associated with lower adherence. We hypothesize that purulence may be seen by house staff as a marker of severity that would more likely be associated with polymicrobial infection. Many of these patients may have had baseline comorbidities that were interpreted as increasing the risk for polymicrobial infection. The presence of purulence as an independent predictor for the use of broad antibiotics was also reported in the study by Jenkins et al.9
The frequent use of empiric antibiotic combinations for MRSA and gram-negative pathogen coverage also contributed to the poor adherence rate. The practice of initiating broad-spectrum coverage appears to be increasing over the years. Berger et al. reported that the use of antibiotics with antipseudomonal activity increased significantly from 16% to 28% between 2000 and 2009.17 Similarly, the use of antibiotics against MRSA significantly increased from 30% to 71% in the same period. Such changes in antibiotic prescribing may stem from concern about the increasing emergence of antimicrobial resistance. However, other than MRSA, there is little evidence of increasing resistance for microbes typically associated with cellulitis. Moreover, numerous centers have noted decreasing rates of MRSA.11
As with many academic health centers, the house staff generates most of the orders for empiric antibiotics. Unfortunately, our antimicrobial stewardship program (ASP) has noted that the education of house staff and consistent monitoring of their antibiotic use is severely hampered by the nature of their medical training. House staff rotate through different services on a frequent basis (most commonly monthly) and through different hospitals. Consequently, provider-specific education and feedback become more difficult. Attempts to implement order sets at our institution have been difficult for similar reasons. Data generated by this study will serve as the basis for broad-based education for all house staff.
The median duration of therapy for cellulitis infection was 12 days in our study. This resulted in a 70% adherence rate to guideline-recommended duration of treatment. The IDSA guidelines recommend that the duration of antibiotics should be five days, but antibiotic treatment should be extended to more than five days if clinical improvement is poor. Severity and possible complications during hospitalization could have contributed to the variation in inpatient therapy duration in
Our study showed variation in empiric antibiotic strategies for the management of cellulitis and substantial noncompliance to evidence-based clinical guideline recommendations. It also highlights an ample need for the development of standardized antibiotic selection protocols in the management of cellulitis. Pasquale et al. reported that interventions made by an ASP resulted in significant reductions in length of stay and 30-day all-cause readmission rates in patients with SSTIs.12
This study has several limitations. The results from this single-center study may not be generalizable to other institutions. Our study was a retrospective chart review, and the diagnosis of nonnecrotizing SSTIs was based on prior chart documentation without prospective criteria for diagnosis and severity classification. In our study, we observed that the treatment approach was always reflective of a severe infection. The rationale behind treating all admitted patients as having severe nonnecrotizing SSTI could be attributed to prescribers following the old 2005 SSTI guideline (which did not clearly distinguish SSTIs as mild, moderate, or severe) or presence of co morbidities (diabetes, IV drug use, recent surgery, prior history of cellulitis, and MRSA infection) and systemic signs of infection and purulent drainage.
An additional limitation is the documentation of readmission rates. The readmission rates reported from the chart review may not be a true representation of treatment failure. Some patients who may have experienced treatment failure could have visited a different hospital for the relapse. For those patients readmitted within 14 days post-discharge, a common observation was that they were hospitalized for an average of about one day. These patients may have received only one or two doses of IV antibiotics prior to discharge the next day. In addition, these patients presented with co morbidities, such as diabetes and previous history of cellulitis infection. Similar observations were present in those readmitted 15 to 30 days post-discharge. Such patients were only hospitalized for about two days and presented with comorbidities of diabetes, peripheral venous disease, and previous history of cellulitis infection. These patients could have benefited from the identification and treatment of predisposing conditions for recurrent cellulitis and prescription of prophylactic antibiotics as recommended by the IDSA guideline. Furthermore, the degree of patient adherence to the prescribed discharge antibiotics could have contributed to readmission.
The study focuses on patients coded with cellulitis at discharge. We did not check the accuracy of the coding prospectively. However, chart review did confirm the presence of a skin and soft tissue condition that was consistent with cellulitis or other nonnecrotizing SSTI. Also, given that our study was conducted within two to 14 months after the publication of the 2014 IDSA guideline on SSTI, another limitation of the study is the expectation that prescribers will change their practice within two to 14 months of a guideline release.8 The literature on adoption of clinical practice guidelines often cites an estimated 17-year time lag in putting new clinical guideline recommendations into practice or translating basic science into patient benefit.19
Finally, the possibility of misdiagnosis among patients reviewed in this study is a potential limitation. Misdiagnosis of cellulitis is a practice gap that needs to be closed with improved diagnostic approach, detailed history and physical examination, more dermatologist consults, and less rush for empiric antibiotic coverage for a potential “infection.” According to a single-center retrospective study by Weng et al., about one-third of patients diagnosed with lower extremity cellulitis at admission were later found to be misdiagnosed either during discharge or during a 30-day follow-up period.18 In that study, patients with complicating factors such as recent surgery, trauma, or diabetic ulcer were excluded. Our study evaluated patients diagnosed with cellulitis in both upper and lower extremities and included patients with complicating factors such as recent surgery.
Incidence of misdiagnosis by clinicians could be attributed to the practice of “defensive medicine” (a tendency to administer antibiotics for a potential infection when faced with uncertain diagnosis of possible cellulitis). Such practice leads to unnecessary antibiotic use and patient exposure to both the therapeutic and potential adverse effects of antibiotics. Unnecessary patient exposure to antibiotics could contribute to the increasing problem of antibiotic resistance. In addition, misdiagnosis could result in unnecessary hospital stays, inefficient utilization of hospital resources, and increased costs.
There is a need for the development and implementation of protocols to promote change in the prescribing patterns of antibiotics in our academic teaching institution. Such an initiative might target antibiotic selection, de-escalation opportunities, and treatment duration in the management of cellulitis. The initiative could also develop easily accessible, standardized educational modules for rotating house staff based on IDSA guidelines. Specific antibiotic selection protocols (perhaps through order sets) could be promoted as well. Ultimately, the ASP should develop tools for antibiotic-use monitoring and feedback to house staff and attending staff on a frequent basis to encourage guideline adherence. Based on the results of our study, the IDSA guidelines have been incorporated into the hospital’s mobile clinical companion application. We have developed both an antibiotic selection pathway and an order set for the management of nonnecrotizing SSTIs. This antibiotic selection pathway has been incorporated into the hospital’s antimicrobial stewardship kit in the mobile clinical companion application. Implementation of such initiatives may improve patient care outcomes and promote better utilization of hospital resources. The impact of the antibiotic selection pathway and an order set on better adherence to IDSA guidelines could be evaluated in future studies.
Figure and Tables
Patient Chart Screening
Baseline Characteristics (N = 208)
|Age in years, mean (range)||43 (18–80)|
|Female, n (%)||65 (31)|
|Male, n (%)||143 (69)|
|Race, n (%)|
|Penicillin allergy, n (%)||20 (10)|
Service Unit at Admission, n (%)
|Infectious disease||1 (0.5)|
|Surgical intensive care unit||1 (0.5)|
|Medical intensive care unit||2 (0.9)|
|Acute care surgery||6 (2.9)|
|Plastic surgery||16 (7.7)|
|Oral and maxillofacial||25 (12.1)|
|Internal medicine||100 (48.3)|
ENT = ear, nose, and throat.
Comorbid Conditions, n (%)
|Intravenous drug user||48 (26)|
|History of cellulitis||37 (20)|
|Peripheral venous disease||11 (6)|
|Recent surgery (≤ 30 days prior to admission)||3 (2)|
|Peripheral artery disease||0 (0)|
Site of Infection, n (%)
|Upper extremities||87 (42)|
|Lower extremities||58 (28)|
Culture and Isolated Pathogen
|Culture, n (%)||Purulent, n (%)||Nonpurulent, n (%)|
|Positive||82 (39.4)||64 (55)||18 (20)|
|Negative||92 (44.2)||42 (36)||50 (55)|
|None||34 (16.3)||11 (9)||23 (25)|
|MRSA||33 (40)||24 (73)||9 (27)|
|MSSA||19 (23)||17 (89)||2 (11)|
|Streptococcus species||13 (16)||8 (62)||5 (38)|
|Gram-negative rods||17 (21)||15 (88)||2 (12)|
MRSA = methicillin-resistant
Empiric Antibiotic Selection
|Initial Empiric Antibiotics||N (%)||% Adherence|
|Vancomycin||128 (61.5)||39/128 = 30.5|
|Piperacillin/tazobactam||111 (53.4)||31/111 = 28|
|Clindamycin||68 (32.7)||38/68 = 55.9|
|Ampicillin/sulbactam||14 (6.7)||5/14 = 35.7|
|Cefazolin||3 (1.4)||2/3 = 66.7|
|Sulfamethoxazole/trimethoprim||3 (1.4)||1/3 = 33.3|
|Penicillin G||1 (0.5)||0|
|83/208 = 39.9|
IDSA = Infectious Diseases Society of America.
Empiric Antibiotic Combinations
|Common Initial Antibiotic Combination||N||Adherence, n (%)|
|Piperacillin/tazobactam and vancomycin||83||31 (37.3)|
|Clindamycin and vancomycin||14||0 (0)|
|Piperacillin/tazobactam and vancomycin and clindamycin||7||0 (0)|
|Piperacillin/tazobactam and vancomycin and ciprofloxacin||2||0 (0)|
|Clindamycin and ciprofloxacin||2||0 (0)|
|Vancomycin and ciprofloxacin||2||0 (0)|
|Piperacillin/tazobactam and metronidazole||2||0 (0)|
|Ciprofloxacin and metronidazole||2||0 (0)|
Prescribed Discharge Antibiotics, n (%)
|Penicillin V||2 (1)|
Duration of Antibiotic Therapy and Cost of Hospitalization
|Days of Antibiotics||Median (range)|
|Total days of antibiotic therapy||12 (1–48)|
|Days of inpatient antibiotics||2 (1–18)|
|Days of outpatient antibiotics||10 (0–30)|
|Adherence to IDSA guideline||70.2%|
|Average cost of hospitalization||$16,618.14|
IDSA = Infectious Diseases Society of America.
Empiric Antibiotic Adherence to IDSA Guideline Recommendation in the Presence of Purulent Infection
|Guideline Adherence||Purulent (n = 117)||Nonpurulent (n = 91)|
IDSA = Infectious Diseases Society of America.
Effects of Variables on Adherence to IDSA Guideline Recommendations
|Independent Variables||Odds Ratio||95% CI|
|Gender (male vs. female)||0.495||0.259–0.944||0.0329|
|Purulence (yes vs. no)||0.203||0.110–0.37||< 0.0001|
CI = confidence interval; IDSA = Infectious Diseases Society of America.
- Chambers H. Pharmacology and the treatment of complicated skin and skin-structure infections. N Engl J Med 2014;370;(23):2238–2239.
- Edelsberg J, Taneja C, Oster G, et al. Trends in US hospital admissions for skin and soft tissue infections. Emerg Infect Dis 2009;15;(9):1516–1518.
- Ray G, Suaya J, Baxter R. Incidence, microbiology, and patient characteristics of skin and soft-tissue infections in a U.S. population: a retrospective population-based study. BMC Infect Dis 2013;13:252
- In: DiPiro JT, Talbert RL, Yee GC, et al. Skin and soft tissue infections. Pharmacotherapy: A Pathophysiologic Approach
8th edNew York, New York: McGraw-Hill Medical. 2011;1899–1902.
- Food and Drug Administration. Guidance for industry: acute bacterial skin and skin structure infections: developing drugs for treatment Available at: www.fda.gov/downloads/Drugs/.../Guidance/ucm071185.pdf. Accessed September 18, 2015
- Hatoum H, Akhras K, Lin S. The attributable clinical and economic burden of skin and skin structure infections in hospitalized patients: a matched cohort study. Diagn Microbiol Infect Dis 2009;64;(3):305–310.
- Lipsky B, Moran G, Napolitano L, et al. A prospective, multicenter, observational study of complicated skin and soft tissue infections in hospitalized patients: clinical characteristics, medical treatment, and outcomes. BMC Infect Dis 2012;12:227
- Stevens D, Bisno A, Wade J, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59;(2):147–159.
- Jenkins T, Knepper B, Burman W, et al. Antibiotic prescribing practices in a multicenter cohort of patients hospitalized for acute bacterial skin and skin structure infection. Infect Control Hosp Epidemiol 2014;35;(10):1241–1250.
- Ohlsen K, Ziebuhr W, Koller K-P, et al. Effects of subinhibitory concentrations of antibiotics on alpha-toxin (hla) gene expression of methicillin-sensitive and methicillin-resistant
Staphylococcus aureusisolates. Antimicrob Agents Chemother 1998;42;(11):2817–2823.
- Sievert D, Ricks P, Edwards J, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infect Control Hosp Epidemiol 2013;34;(1):1–14.
- Pasquale T, Trienski T, File T, et al. Impact of an antimicrobial stewardship program on patients with acute bacterial skin and skin structure infections. Am J Health Syst Pharm 2014;71;(13):1136–1139.
- Fraser G, Stogsdill P, Dickens J, et al. Antibiotic optimization. An evaluation of patient safety and economic outcomes. Arch Intern Med 1997;157;(15):1689–1694.
- Quirke M, Wakai A. Treatment outcome measures for randomized controlled trials of antibiotic treatment for acute bacterial skin and skin structure infections in the emergency department setting. Int J Emerg Med 2015;8:11
- Eron L, Lipsky B, Low D, et al. Managing skin and soft tissue infections: expert panel recommendations on key decision points. J Antimicrob Chemother 2003;52;(suppl 1):i3–i17.
- Hepburn M, Dooley D, Skidmore P, et al. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med 2004;164;(15):1669–1674.
- Berger A, Edelsberg J, Oster G, et al. Patterns of initial anti biotic therapy for complicated skin and skin structure infections (cSSSI) in U.S. hospitals, 2000–2009. Infectious Diseases in Clinical Practice 2013;21;(3):159–167.
- Weng QY, Raff AB, Cohen JM, et al. Costs and consequences associated with misdiagnosed lower extremity cellulitis. JAMA Dermatol 2017;153;(2):141–146.
- Morris ZS, Wooding S, Grant J. The answer is 17 years, what is the question: understanding time lags in translational research. J R Soc Med 2011;104;(12):510–520.