Current Microbiology of Surgical Site Infections Associated With Breast Cancer Surgery

Abstract: Surgical site infections (SSI) are the most common complications of breast cancer surgery. The authors identified 35 cases of SSI in the M.D. Anderson Cancer Center (Houston, TX) over a 7-month study period. Monomicrobial infections predominated (69%) with Staphylococcus aureus being isolated most often. A wide variety of gram-positive and gram-negative organisms were isolated from the 31% of polymicrobial infections, suggesting the need for broad-spectrum coverage at least until culture results become available. Although all S aureus isolates were susceptible to vancomycin (minimal inhibitory concentration [MIC] ≤ 2.0 µg/mL), 63% of methicillin-susceptible isolates and 82% of methicillin-resistant isolates had MIC values of ≥ 1.0 µg/mL for this agent, indicating the need for alternative therapeutic agents. The organisms were susceptible to trimethoprim/sulfamethoxazole, rifampin, linezolid, daptomycin, and tigecycline.
Address correspondence to: Kenneth Rolston, MD 1515 Holcombe Blvd., Unit 1460 Houston, TX 77030 Phone: 713-792-043 Email: krolston@mdanderson.org
     Breast cancer is one of the most frequent malignancies in women worldwide. Excision of the primary tumor (by mastectomy or breast-conserving surgery) and sentinel lymph node or axillary lymph node dissection are standard procedures for the treatment of most cases.¹ In the United States, approximately 200,000 breast cancer surgical procedures are performed annually. The frequency of infection following such procedures is estimated to be between 4% and 8%, which translates to an annual figure of 8000 to 16,000 cases.² Episodes of infections are associated with considerable morbidity and increased healthcare costs.³ Infection prevention and prompt treatment using appropriate antimicrobial agents based on local microbiology and susceptibility/resistance patterns is desirable. Consequently, the authors decided to determine the current microbiology of infections associated with breast cancer surgery at the authors’ institution, a National Cancer Institute (NCI) designated comprehensive cancer center.

Materials and Methods

     The authors’ institution is a 500-bed comprehensive cancer center devoted exclusively to the care of patients with cancer. All microbiological samples are submitted to and processed by a central microbiology laboratory. A retrospective review was conducted of the computerized records of the institution’s microbiology laboratory in order to identify episodes of infection associated with breast cancer surgery over a 7-month period (January 2009–August 2009). Only one episode of infection per patient was included in this survey. Microbial identifications were performed using established criteria according to standard clinical methods.⁴ Enterobacteriaceae and most facultative anaerobes were identified using the Vitek 1 System (BioMerieux, Marcy l’Etoile, France). For organisms with questionable identification, 16S sequencing was used.⁵ Susceptibility testing was performed using the Vitek 1 System using GPS card 119 and GNS card 132 and 134, or the E-test method for non-fermenters, fastidious organisms, and enterococci (AB Biodisk, Solna, Sweden). Interpretive standards for susceptibilities were derived from CLSI, M100-S18, M7-A7, and M2-A10.⁶

Results

     A total of 35 cases of surgical site infection following breast cancer surgery were identified. Microbiological details are shown in Table 1. Twenty-four episodes (69%) were monomicrobial and 11 (31%) were polymicrobial. Methicillin-susceptible Staphylococcus aureus (MSSA) accounted for 10 (42%) of the monomicrobial episodes, 9 (37%) by methicillin-resistant S aureus (MRSA), and 5 (21%) by beta-hemolytic streptococci. Staphylococci (9-MSSA and 2-MRSA) were also isolated from all 11 episodes of polymicrobial infection. Other organisms isolated from polymicrobial infections included Escherichia coli (5), Proteus mirabilis and Corynebacterium spp (2 each), Group B Streptococcus, Enterococcus spp, Klebsiella oxytoca, and Pseudomonas aeruginosa (1 each).      Susceptibility data are shown in Table 2 and Figures 1 and 2. All 19 methicillin susceptible S aureus isolates were susceptible to vancomycin. However, 12 of these isolates (63%) had a minimal inhibitory concentration (MIC) of ≥ 1.0 µg/mL. Similarly, although all 11 MRSA isolates were susceptible to vancomycin, 9 (82%) had vancomycin MICs of > 1.0 µg/mL. All staphylococcal isolates (MSSA and MRSA) were also susceptible to linezolid, trimethoprim/sulfamethoxazole, and rifampin. A limited number of staphylococci (< 25% of isolates) were tested for susceptibility to the newer agents daptomycin and tigecycline. All were susceptible using the E-test methodology.      All 5 streptococcal isolates were susceptible to vancomycin, linezolid, TMP-SMX, and rifampin. The 5 streptococcal isolates were also susceptible to the quinolones (eg, moxifloxacin) and macrolides (eg, azithromycin). Among the 5 E coli isolates, 2 (40%) were resistant to the quinolones and TMP/SMX, but were susceptible to the aminoglycosides, cepholosporins, and carbapenems. All other gram-negative isolates (Klebsiella oxytoca, Proteus mirabilis, and P aeruginosa) were susceptible to the aminoglycosides, quinolones, and beta-lactam agents.

Discussion

     Surgical site infection (SSI) is the most common postoperative complication associated with breast cancer surgery.⁷ The development of SSI can lead to prolonged hospital stay with increased costs, poor cosmetic results, psychological trauma, and occasionally, a delay in postoperative adjuvant therapies.⁸ One study estimated increased costs attributable to SSI following breast cancer surgery to be $4091.¹³ Studies have shown that delaying postoperative radiotherapy results in poorer control of local diseases.⁹ A significant increase in metastatic relapse and reduced survival exist when adjuvant chemotherapy is delayed.¹⁰ Consequently, infection prevention and prompt, effective therapy once infection develops are important strategies in the overall management of such patients. Not all patients who undergo breast cancer surgery have the same risk of SSI development. Some studies have shown that prior chemotherapy and immediate breast reconstruction are associated with an increased risk of infection.¹¹ Antimicrobial prophylaxis has been recommended for such patients. Knowledge of local microbiology and susceptibility/resistance patterns need to be considered when choosing agents that will be suitable for the prevention and treatment of these infections.      The prevalence of gram-positive organisms including multidrug resistant strains such as MRSA has become common in patients with cancer, particularly patients with neutropenia.¹² Vancomycin has been the cornerstone of therapy for resistant gram-positive infections for several decades.¹³ Over the past few years, delayed responses to vancomycin and overt treatment failures have been reported from immunosuppressed and immunocompetent patients despite the in-vitro susceptibility of the organisms to vancomycin.^14,15 Some institutions have reported declining in-vitro activity of vancomycin (the so-called MIC creep) against both MSSA and MRSA.¹⁶ Several investigators have reported on the relationship of vancomycin MICs to its bactericidal activity and clinical efficacy with MIC values of ≥ 1.0 µg/mL being associated with decreased bactericidal activity and clinical failures.^14,15 Tolerance of clinical isolates to vancomycin (defined as a minimum bactericidal concentration ≥ 32-fold the MIC) appears to be another mechanism associated with declining vancomycin activity.¹⁷      Data from the present study provide confirmation that gram-positive bacteria, particularly MSSA and MRSA, remain the primary pathogens isolated from SSI following breast cancer surgery. However, the frequency of polymicrobial infections in this setting (31% in the present study) was surprising. Gram-negative bacilli were isolated from a high proportion of these polymicrobial infections suggesting the need for broad-spectrum antimicrobial coverage—at least until culture results became available. However, the authors’ main concern was that 63% of the MSSA isolates and 92% of MRSA isolates had vancomycin MICs of ≥ 1.0. These data suggest that vancomycin may no longer be a suitable agent for the majority of SSIs at the authors’ institution. Newer agents such as daptomycin and telavancin have been shown to be more potent and have superior bactericidal activity over vancomycin.¹⁸ Such agents will probably be used more often than vancomycin at institutions such as the authors’. Fortunately, most of our MSSA and MRSA isolates remain susceptible to older agents including TMP/SMX, doxycycline, and rifampin. While newer agents such as daptomycin and tigecycline are suitable alternatives to vancomycin it is not always the case, and highlights the need to conduct local epidemiological surveys and susceptibility surveillance studies.

Conclusion

     MSSA and MRSA are the predominant cause of SSIs following breast cancer surgery. Current susceptibility data from the authors’ institution indicate that vancomycin may no longer be a potent agent to treat these infections, as the majority of these isolates have an MIC of ≥ 1.0 µg/mL. The frequency of polymicrobial infections was surprisingly high (31%), indicating the need for broad-spectrum antibacterial coverage in this setting.