Infection with an Extended-Spectrum β-Lactamase-Producing Strain of Serratia marcescens following Tongue Reconstruction

Abstract

We report a case of postsurgical wound infection of polymicrobial etiology caused by Serratia marcescens and Pseudomonas aeruginosa following the use of a radial forearm free flap for oncological tongue reconstruction. S. marcescens was a producer of SHV-12 extended-spectrum β-lactamase (ESBL). This is the first report from India of this ESBL. S. marcescens and P. aeruginosa were resistant to the empirical perioperative antibiotics administered. Delay in the recognition of the type of infection and in the institution of appropriate therapy resulted in total loss of the free flap.

CASE REPORT

A 39-year-old man was admitted to the surgical oncology ward of the All India Institute of Medical Sciences (New Delhi, India) with a history of a nonhealing ulcer of 1-year duration on the left side of the tongue. An initial examination revealed a 0.5- by 1-cm indurate area on the left ventrolateral surface of the tongue. A biopsy was performed which showed a well-differentiated squamous cell carcinoma of the left lateral border of the tongue. The tumor was classified as stages T1, N1, and M0.

The patient underwent operative treatment consisting of left hemiglossectomy and unilateral supraomohyoid neck dissection. This was followed by reconstruction of the tongue with a radial forearm free flap. An initial regimen of metronidazole, amoxicillin, and clavulanic acid was started postoperatively.

Ten days later, there were signs of collection of pus at the postoperative wound site. The pus was drained and sent for bacterial culture. Consecutive cultures obtained from the wound yielded growth of Serratia marcescens and Pseudomonas aeruginosa. S. marcescens is an opportunistic gram-negative bacterium that is associated with sporadic urinary tract infections and pneumonia in patients in intensive care units, although outbreaks can occur (1).

Antibiotic susceptibility profiles were done by using a standard disk diffusion method recommended by the NCCLS (7). P. aeruginosa was susceptible to ciprofloxacin, ceftazidime, cefpirome, piperacillin-tazobactam, and cefoperazone-sulbactam. It was resistant to amoxicillin-clavulanic acid, piperacillin, cefotaxime, and amikacin. S. marcescens exhibited resistance to piperacillin, cefotaxime, ceftazidime, ceftriaxone, cefoperazone, cefpirome, amikacin, netilmicin, ciprofloxacin, and amoxicillin-clavulanic acid. It was sensitive to piperacillin-tazobactam and cefoperazone-sulbactam. The strain tested positive, by the method described by the NCCLS (7), for the production of extended-spectrum β-lactamase (ESBL).

Isoelectric focusing and gene sequencing characterized the ESBL. Isoelectric focusing was performed with polyacrylamide gels containing Ampholine with a pH range of 3.5 to 10 as previously described (2). β-lactamases of known isoelectric points (pIs), TEM-1 (pI 5.4), TEM-2 (pI 5.6), TEM-24 (pI 6.5), SHV-5 (pI 8.2), and CTX-M-1 (pI 8.4), were used as standards. Isoelectric focusing showed that the ESBL focused at a pI of 8.4, suggesting that the ESBL of the S. marcescens strain was an SHV-type β-lactamase. Positive amplification was obtained with primers SHVA (5′-3′) and SHVB (5′-3′), which amplify the complete sequence of the SHV-type genes. Direct DNA sequencing of PCR products (2) showed that the SHV-type gene encoded the ESBL SHV-12, which was first described in 1997 in an Escherichia coli strain isolated in Switzerland (8).

The antibiotic treatment was changed to a parenteral combination of cefoperazone and sulbactam in an attempt to control the infection of the free flap. Samples from the patient's environment, including swabs from the dressing trolley, bed railing, mattress, in-use antiseptic solutions, intravenous fluids, and intravenous infusion sets used in the patient, were collected. The hospital water supply was also tested. Swabs from the hands of personnel attending the patient were collected to determine the source of infection. All the samples were found by culture to be negative.

Despite the change to the appropriate antimicrobial therapy, the radial forearm free flap could not be salvaged and total loss of the flap occurred as a result of infection.

Patients with cancer of the upper aerodigestive tract who undergo surgical resection of the neoplasm and reconstruction of the defect with a tissue flap have a high incidence of wound infection. Despite perioperative treatment with systemic antibiotics, reported wound infection rates in this group range from 20 to 25%, compared with wound infection rates of 5 to 10% in patients undergoing contaminated head and neck surgery without flap reconstruction (3, 11).

Our patient developed postoperative flap infection, which was polymicrobial in etiology. Both the organisms isolated were gram-negative aerobes. Among patients hospitalized for prolonged periods, those who are debilitated, or those who have head and neck cancers, the microflora may be altered by the emergence of gram-negative aerobic organisms (4).

Prophylactic perioperative antibiotics have been proven to be mandatory with contaminated head and neck surgery. Although the amoxicillin-clavulanic acid combination used for our patient provides coverage for both gram-positive and gram-negative organisms in addition to anaerobic organisms, it was ineffective against both S. marcescens and P. aeruginosa, which were cultured from the wound and were multidrug resistant. The delay in the submission of cultures for the detection of these resistant organisms resulted in the delay in the initiation of appropriate therapy, contributing to the flap failure.

The S. marcescens strain isolated from our patient was an ESBL producer. ESBL producers have most commonly been documented among Klebsiella pneumoniae and E. coli strains and less commonly among other members of the family Enterobacteriaceae, such as Serratia species (9). Putative ESBL-producing bacteria have been detected in India (6), but only ESBLs CTX-M-15 and SHV-5 have been characterized (5, 10). This is therefore the first report of an SHV-12-producing S. marcescens strain isolated in India.

In conclusion, perioperative vigilance and the timely submission of properly obtained cultures should make it possible to recognize infection with resistant bacteria and treat with appropriate antibiotics, thereby reducing the incidence of postoperative wound infections.