Summary
Septic arthritis is classified among the acute emergencies of joint diseases. Gram-positive cocci are responsible in 75-80% of the cases, while Gramnegative bacilli may be the etiological agents in case of compromised immunity, intravenous drug abuse, advanced age, or iatrogenic infections. Cases of posttraumatic septic arthritis due to Gram-negative bacilli in immunocompetent patients are reported in the literature. In this paper we present a severe septic arthritis due to Serratia marcescens in a 43-year-old man with multiple trauma, right patellar and femoral condyle fracture after a traffic accident, three days after an irrigation and debridement procedure was performed. The surgical procedure had to be repeated four times while he was receiving medical treatment. A literature search in PubMed using the keywords "Serratia marcescens and septic arthritis" on October 10th 2017, we found 37 articles, of which 18 were case reports or case series. Of those 18 articles, seven cases were hospital-acquired, five were in intravenous drug users, two were trauma related, one was concomitant with rheumatoid arthritis, one was in a neonate, one was due to intra-articular injection, and one article described an epidemic due to usage of contaminated benzalkonium chloride solution as an antiseptic. We also found a case by searching Turkish Medline reported in a ten-week-old baby with Escobar syndrome. In our case, although hospital-acquired infection cannot be ruled out, we believe that this was a community-acquired infection due to contamination of the open dirty wound, as the irrigation procedure was done in sterile operating room conditions and no other such case has ever been identified. As prompt diagnosis and treatment is critical in prognosis of septic arthritis, we emphasize the possible role of Gram-negative bacilli in posttraumatic cases.
Introduction
Septic arthritis is inflammation of the synovial membrane and synovial fluid (SF) of the joints caused by bacterial, viral, or fungal agents. The synovial membrane is a highly vascular structure; however, it is to prone to infections due to the lack of a basement membrane[1]. Risk factors include the presence of rheumatoid arthritis, diabetes, hypogammaglobulinemia, chronic liver/kidney disease, cancer, alcoholism, and advanced age, as well as undergoing joint aspiration or surgery and receiving immunosuppressive therapy[2, 3]. The knee joint is reported in nearly all studies as the most commonly affected joint, accounting for 45% of the cases on average[4]. Septic arthritis is classified as an emergent articular disease and early diagnosis and treatment are of great importance in terms of prognosis. With early treatment, approximately 80% of patients recover with no sequelae, whereas this is 30% less likely in those treated seven days later[5]. The definitive diagnosis is established by macroscopic, microscopic, microbiological, and biochemical evaluation of SF aspirated in sterile conditions. Leukocyte count over 50,000/mm3 and polymorphonuclear leukocyte (PNL) ratio over 80% in SF are findings in favor of acute bacterial infection[6]. Gram-positive bacteria are seen at rates of 75- 80%, Gram-negative bacteria at 40-50%, and gonococci at 20- 25% in Gram staining. SF cultures are positive in about 60% of cases on average, and diagnosis is established with SF and blood culture in another 14%, demonstrating the importance of obtaining blood culture in addition to SF[7]. Immediately following diagnosis, purulent fluid in the joint should be drained and the infection should be treated with appropriate antibiotics. The infectious agent varies according to the pathogenesis of the infection and host risk factors. The most common etiologic agents are Gram-positive cocci in 75-80% and Gram-negative bacilli in 10-15% of cases[8, 9]. In particular, Staphylococcus aureus is the most common cause of septic arthritis because it contains surface adhesion molecules linked to extracellular matrix proteins[10]. However, Gram-negative bacilli may be the infectious agent in immunocompromised patients, intravenous drug addicts, and elderly or iatrogenic cases[8, 9]. These cases develop more extensive joint destruction, higher incidence of sequelae, and longer treatment duration[11]. In this case report and review, we present a case of septic arthritis due to Serratia marcescens in an immunocompetent patient and emphasize that Gram-negative bacilli should be considered as the etiologic factor in posttraumatic septic arthritis.
Case Report
Literature Review
Septic arthritis due to Serratia, a Gram-negative bacteria, is rarely encountered. A PubMed search conducted on October 10th, 2017 using the keywords "Serratia marcescens" and "septic arthritis" yielded 37 articles; as a result of the literature review, 14 papers in English or Turkish involving cases of septic arthritis due to S. marcescens which were not part of reviews, veterinary literature, or other repeated cases (e.g. as part of drug addiction case series) were analyzed, and they are presented with possible sources of infection, treatment, and outcomes in Table 1[13, 16-21, 23-29]. In addition, one case was found in the Turkish Medical Directory using the key words "Serratia" and "septik artrit". Primary S. marcescens septic arthritis was first reported by Atlas and Belding[13] in 1968 in JAMA in a 62-year-old woman with severe diabetes and urinary tract infection due to S. marcescens. The authors pointed out the rapid and destructive progression to amputation despite the treatment with kanamycin, to which the infecting strain was susceptible[13]. In the literature, this agent is usually reported in patients with nosocomial infection or severe immunosuppression[13-16]. Epidemic S. marcescens arthritis was first reported by Nakashima et al.[17] as an iatrogenic infection in ten patients using contaminated benzalkonium chloride antiseptic agent. Ross et al.[18] isolated S. marcescens in four intravenous heroin addicts in 1975, thus highlighting the relative prevalence of the pathogen among drug addicts for the first time. An immunocompetent case with no history of hospital admission or drug addiction was first reported by Lafuente Martinez et al.[19] in 1981 in a 17-yearold patient, and the authors noted that the agent had been increasingly isolated in recent years. Hadid et al.[20] reported septic arthritis in the ankle in an article entitled "Severe Osteomyelitis and Septic Arthritis due to Serratia marcescens in an Immunocompetent Patient" and emphasized that the etiology was rare. However, they stated that the patient was 72 years old and had uncontrolled diabetes, and that because he played golf, he may have acquired the agent from the soil after a minor trauma. There are also reports in the literature of arthritis due to Gram-negative bacteria and polymicrobial factors after trauma. Chiu and Wang[21] isolated S. marcescens in knee arthritis in an immunocompetent patient following a motorcycle accident. As in our case, that patient was initially treated empirically for Gram-positive agents, then switched to ciprofloxacin based on the culture results, and arthrotomy/ arthroscopy and debridement were done four times before negative culture was obtained. The patient had severe limitation of motion in the joint after treatment and was referred to an intensive physiotherapy program. The authors emphasized the difficulty of eradicating the agent in Gram-negative arthritis, and the importance of surgical debridement, early selection of appropriate antibiotics, and intensive physiotherapy. This year, for the first time in Turkey, Sandal et al.[22] from İzmir Dr. Behçet Uz Children"s Hospital reported septic arthritis of the knee due to S. marcescens in a ten-week-old baby with Escobar syndrome. The patient had no permanent deformity after six weeks of meropenem treatment, which the authors attributed to early diagnosis, urgent aspiration, appropriate empirical treatment, and the initiation of joint opening exercises and muscle stretching exercises to prevent deformity.
Discussion
It is known that septic arthritis caused by Gram-negative bacteria has a poorer prognosis. It has been reported that longer treatment duration is necessary because treatment response is lower and complications such as ankylosis, secondary osteomyelitis, flexion contracture, chronic effusion, and recurrent infections are more common[10, 11]. Septic arthritis due to Gram-negative bacilli in immunocompetent patients is rare, and has been reported in the literature as case reports or case series[10, 11, 14-17]. Lin et al.[14] reported in a series of 194 septic arthritis cases of which 48 (24.7%) were due to Gramnegative bacteria. In the same series, 56.3% of the patients had at least one underlying immunosuppressive condition, 29.2% had gut disease, and 62.5% were over 65 years of age. The authors emphasized that broad-spectrum antibiotherapy that cover Gram-negative bacteria should be considered, especially in immunosuppressed and/or older patients.
In our case, S. marcescens was identified as the etiologic agent of septic arthritis in an immunocompetent patient who presented with open/dirty wound after trauma. Like other members of the Enterobacteriaceae family, S. marcescens is naturally resistant to penicillin G, macrolides, clindamycin, linezolid, glycopeptides, and quinupristin/dalfopristin. Serratia spp. are also generally resistant to ampicillin, amoxicillin, amoxicillin-clavulanate, ampicillin-sulbactam, first generation cephalosporins, cefuroxime, nitrofurantoin, colistin, and tetracyclines[29, 31]. Therefore, it is recommended to start treatment for Serratia infections with piperacillin-tazobactam, fluoroquinolone, or carbapenem and to adjust treatment if necessary according to antibiotic susceptibility pattern[16].
Although no SF sample was taken during the first debridement/ washing procedure and the case was consistent with definitions of nosocomial septic arthritis, we believe that this was a case of community-based septic arthritis resulting from contamination of an open/dirty wound, because the procedure was performed in sterile operating room conditions and we have never encountered such complications after this frequently performed procedure[32].
Since our patient presented with a dirty wound, treatment was started with cefazoline + gentamicin as is routine in our orthopedic clinic. When arthritis appeared after three days and Gram-negative bacilli were observed in the SF, treatment was changed to piperacillin-tazobactam in accordance with treatment guidelines. There was still no response to treatment after one week, leading us to suspect low generic antibiotic activity, so ertapenem treatment was started and continued for four weeks. Gram-positive agents, especially S. aureus, are the first to come to mind in community-acquired septic arthritis, and empirical treatment usually targets these microorganisms. Therefore, it is observed in the literature that there is a delay of 3-21 days (mean 12 days) in the diagnosis of septic arthritis, mostly due to Gram-negative bacteria[8, 33]. It should be kept in mind that delayed or inappropriate treatment lead to more serious complications in septic arthritis, especially with more aggressive Gram-negative agents, and that Gram-negative bacteria such as S. marcescens may be the etiologic factor in posttraumatic arthritis, even in the absence of an underlying immunosuppressive condition.
Ethics
Informed Consent: Consent form was filled out by the reported case.
Peer-review: Externally and internally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: A.I.O., A.A., S.T., Analysis or Interpretation: A.I.O., B.Ş., H.E., Literature Search: A.I.O., B.Ş., T.A, Writing: A.I.O.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.