Background
Pseudomonas aeruginosa has traditionally been considered a common pathogen in diabetic foot infection (DFI), yet the 2012 Infectious Diseases Society of America guideline for DFI states that “empiric therapy directed at P aeruginosa is usually unnecessary.” The objective of this study was to evaluate the frequency of P aeruginosa isolated from bone or tissue cultures from patients with DFI.
Methods
This study is a cross-sectional survey of diabetic patients presenting with a foot infection to an urban county hospital between July 1, 2012, and December 31, 2013. All of the patients had at least one debridement procedure during which tissue or bone cultures from operative or bedside debridements were obtained. The χ2 test and the t test of means were used to determine relationships between variables and the frequency of P aeruginosa in culture.
Results
The median number of bacteria isolated from DFI was two. Streptococcus spp and Staphylococcus aureus were the most commonly isolated organisms; P aeruginosa was isolated in only five of 112 patients (4.5%). The presence of P aeruginosa was not associated with the patient's age, glycosylated hemoglobin level, tobacco abuse, the presence of osteomyelitis, a prescription for antibiotic drugs in the preceding 3 months, or the type of operative procedure.
Conclusions
Pseudomonas aeruginosa was an infrequent isolate from DFI in this urban, underserved diabetic population. The presence of P aeruginosa was not associated with any measured risk factors. By introducing a clinical practice guideline, we hope to discourage frontline providers from using routine antipseudomonal antibiotic drugs for DFI.
Pseudomonas aeruginosa has traditionally been considered a common pathogen in diabetic foot infection (DFI), and it accounts for 9.3% to 31% of DFI in the literature.1-12 However, the importance of this pathogen has recently been questioned. The 2012 Infectious Diseases Society of America (IDSA) guideline for DFIs states that “empiric therapy directed at P aeruginosa is usually unnecessary except for patients with risk factors for true infection with this organism.”13(p. e147) Risk factors cited by the IDSA for P aeruginosa include a high local prevalence of P aeruginosa infection, a warm climate, and frequent exposure of the foot to water.13
The IDSA recommendation is based on three factors. First, the incidence of P aeruginosa as a cause of DFI in developed countries outside of the tropics seems to be low.1,2 Second, there is increasing evidence that clinical cure of polymicrobial skin and soft-tissue infections that include P aeruginosa can occur in the absence of antibiotic agents that cover this organism.14-17 Third, P aeruginosa often is a colonizer of open wounds. The objective of this study was to determine the frequency with which P aeruginosa was isolated from patients hospitalized with DFI. This information may then be used to determine whether antipseudomonal antibiotic drug therapy is indicated for DFI at this facility.
Methods
Study Setting and Population
This study is a cross-sectional survey of diabetic patients presenting with a foot infection to an urban county hospital in Denver, Colorado, between June 1, 2012, and December 31, 2013. Patients were eligible for inclusion if they were diabetic and were referred to the orthopedic infectious diseases consultation service or the outpatient musculoskeletal infections clinic for evaluation of a suspected foot infection. In addition, patients must have undergone at least one debridement procedure, either at the bedside or in the operating room. Microbiological specimens included bone and tissue swabs; all of the wound swabs were excluded from the analyses. Children younger than 18 years were excluded from the study, as were patients who were found to have an uninfected foot wound according to the IDSA classification.13 Some patients presented with more than one distinct episode of DFI during the study period; to avoid sampling bias, subsequent DFIs were excluded.
Definitions
The IDSA infection severity criteria were used to classify DFIs in this study. The IDSA defines infections by the presence of at least two of the following items: local swelling or induration, erythema, local tenderness or pain, local warmth, and purulent discharge. Mild infections are defined as those including the skin and subcutaneous tissue without involvement of deeper tissues; erythema must be 0.5 to 2 cm around the ulcer. Moderate infections are those involving structures deeper than the subcutaneous tissue or erythema greater than 2 cm. Severe infections are defined as a local infection plus at least two signs of systemic inflammation, including temperature greater than 38°C or less than 36°C, heart rate greater than 90/min, respiratory rate greater than 20/min, and leukocyte count greater than 12,000 or less than 4,000 cells/μL.13
The National Healthcare Safety Network criteria were used to diagnose osteomyelitis. The National Healthcare Safety Network defines osteomyelitis as 1) organisms cultured from bone; 2) evidence of osteomyelitis on direct examination of the bone during an invasive procedure or histopathologic examination; or 3) the presence of at least two signs of infection (fever >38°C, localized swelling, tenderness, heat, or drainage at the suspected site of bone infection) plus an organism cultured from blood, a positive laboratory blood test result, or an imaging test with evidence of infection.18
Toe amputation was defined as any partial or full amputation of a digit. Metatarsal amputation included a partial or full amputation of a digit plus a portion of the corresponding metatarsal. Transmetatarsal amputation consisted of all five metatarsals transected at the midshaft or proximal. Incision and debridement was a surgical procedure that did not include amputation of bone but may have included bone biopsy. Calcaneal debridement included partial or full resection of the calcaneus.
Microbiological Methods
Tissue or bone specimens were obtained by operative or bedside debridement. Specimens were transported to the clinical microbiology laboratory in sterile containers, were processed per routine laboratory protocol, and were set up for both aerobic and anaerobic bacterial cultures. Aerobic media plates were incubated at 35°C and checked daily for growth for 5 days. Anaerobic media plates were incubated at 35°C in an anaerobic environment and checked daily for growth beginning on the second day for 5 days. Isolates were identified using biochemical testing.
Data Collection
Data were prospectively entered into a research electronic data capture database developed for use in patient tracking and monitoring.19 Incomplete information was manually reconciled through review of the medical record. Variables of interest included demographic information, medical and social history, surgical management, microbiology specimen types and results, pathology results, radiology results, and antibiotic drugs prescribed in the 3 months before DFI culture.
Statistical Analysis
Descriptive statistics were used to determine the frequency of isolates present in DFIs. The χ2 test was used to determine whether there were associations between categorical variables and outcomes of interest; the t test of means was used to evaluate continuous variables and the outcomes of interest. All of the analyses were performed using SAS version 9.3 (SAS Institute Inc, Cary, North Carolina). The Colorado Multiple Institutional Review Board deemed this study exempt from human subjects review.
Results
One hundred thirty patients with suspected DFI were referred to the orthopedic infectious diseases consultation service or the musculoskeletal infections clinic during the study period. Thirteen patients were found to be uninfected by IDSA classification, and an additional five had only a wound swab, not tissue or bone, sent for microbiologic culture. Thus, 112 patients were included in the analyses. Patients had a mean age of 55.9 years and a mean glycosylated hemoglobin level of 9.5%. Twenty-seven patients (24.1%) used tobacco. Eighty patients (71.4%) were diagnosed as having osteomyelitis. Surgical procedures included toe amputation (n = 40, 35.7%), metatarsal amputation (n = 29, 25.9%), incision and drainage (n = 23, 20.5%), transmetatarsal amputation (n = 17, 15.2%), and calcaneal debridement (n = 3, 2.7%).
The median number of isolates per patient with DFI was two; 28 infections (25.0%) were due to a single organism; all of the P aeruginosa infections were polymicrobial. Streptococcus spp and Staphylococcus aureus were the most commonly isolated organisms, present in 48.2% and 42.9% of DFIs, respectively. Enterobacteriaceae were present in 21.4% of DFIs, whereas P aeruginosa was isolated from only five patients (4.5%) with DFI (Table 1). The presence of P aeruginosa was not associated with the patient's age, glycosylated hemoglobin level, tobacco abuse, homelessness, antibiotic drugs prescribed in the preceding 3 months, the presence of osteomyelitis, IDSA infection classification, or location of operative intervention (Table 2).
Bacteria Isolated from Bone and Tissue Cultures of 112 Patients with a Diabetic Foot Infection
Patient Characteristics with and Without Pseudomonas aeruginosa Isolated from Deep Tissue Culture of Diabetic Foot Infection
Discussion
Pseudomonas aeruginosa was a relatively uncommon cause of DFI in this urban, underserved diabetic population in the United States. Other pathogens, such as Streptococcus and S aureus were more prevalent. Substantial variation in the incidence of P aeruginosa is present in the literature. Authors from underdeveloped tropical countries report higher rates of P aeruginosa in DFIs (12%–31%)3-12 than authors in nontropical developed countries (9.3%–9.8%).1,2 Although the present data are more consistent with those of other authors from developed countries, the rate of P aeruginosa in this study population is even lower than that in previous reports. This study was unable to determine risk factors for P aeruginosa because the number of patients presenting with P aeruginosa DFI was insufficient to make statistical inferences.
Pseudomonas aeruginosa can be a difficult bacterium to treat. Relatively few antibiotic drugs cover this organism, and commonly used antipseudomonal antibiotic agents, such as fluoroquinolones, fourth-generation cephalosporins, and carbapenems, are broad-spectrum agents. With the low incidence of P aeruginosa and evidence that clinical cure of polymicrobial P aeruginosa DFI may not require antipseudomonal antibiotic drugs,14-17 we are faced with how to change the prescribing practices of frontline providers. Clinical practice guidelines standardize care for common conditions and have been shown to decrease unnecessary antibiotic drug use.20 Our facility has developed a clinical practice guideline for DFI approved by a multidisciplinary group of physicians. We hope that this guideline will assist frontline providers in minimizing unnecessary broad-spectrum antibiotic drug exposure while still ensuring optimal patient outcomes. Limiting the use of antipseudomonal antibiotic drugs may also help prevent the emergence of resistant gram-negative bacteria at this facility.21,22
This study is limited by referral bias. Most cases included in this study were moderate and severe DFIs that required surgical intervention. We are unable to determine whether P aeruginosa is a common pathogen in mild DFI.
Conclusions
This study finds P aeruginosa to be a rare isolate from DFIs in an urban, underserved diabetic population. The presence of P aeruginosa was not associated with any measured risk factors. By introducing a clinical practice guideline, we hope to discourage frontline providers from routinely prescribing antipseudomonal antibiotic agents for DFIs.
Financial Disclosure: None reported.
Conflict of Interest: None reported.
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