Bacteriology and mortality of necrotizing fasciitis in a tertiary coastal hospital with comparing risk indicators of methicillin-resistant Staphylococcus aureus and Vibrio vulnificus infections: a prospective study

Necrotizing fasciitis (NF) is a life-threatening soft tissue infection with a high mortality rate of 25.3–73% [1‐3]. Early suspicion of NF with emergent surgical debridement and appropriate antibiotic therapy can increase the survival rates and clinical outcomes [4, 5]. To improve the NF diagnosis, several clinical features had been recommended in the clinical diagnosis, including bullae, purple skin discoloration, crepitus, gas on X-Ray, local pain, swelling, erythema, tachycardia, fever, hypotension, and tachypnea [6‐9]. NF is generally due to external trauma or skin wound that occurs commonly in patients with pre-existing chronic underlying diseases; however, diabetes mellitus, immunosuppression, chronic renal failure and decompensated liver disease have been reported as the major co-morbidities with poor prognosis in NF patients [6‐10].

Depending on microbiological findings, NF is classified into four types—Polymicrobial infection (type I) with signs and symptoms of severe septic shock and multiple organ dysfunction was believed to be the first cause of NF, and followed by group A Streptococcus infection alone or combined with Staphylococcus aureus (type II) [1‐10]. However, several studies have found that S. aureus, with or without methicillin resistanc, has emerged as an important monomicrobial infection type for NF [6‐15]. Meanwhile, the marine bacterial infection related NF, such as Vibrio species, Aeromonas or Klebsiella species, have been noted as type III, and the fungal infection have been classified as type IV [1‐7, 15‐18].

In a 10-year study from 2003 to 2013, Streptococcus (48%), Staphylococcus (22%), and Gram-negative bacteria (21%) were the main pathogens to cause death in the patients with NF in the U.S., while monomicrobial NF due to either Staphylococcus or Streptococcus contributed to 69% of deaths with identified microorganisms [11]. In the past decade, methicillin-resistant Staphylococcus aureus (MRSA) was evidenced as an important emerging monomicrobial pathogens with a high mortality rate of up to 15% with a general increasingly range from 4 to 23% [12‐15]. Furthermore, MRSA infection has caused a higher amputation rate in patients with deep-seated infection than methicillin-sensitive Staphylococcus aureus (MSSA) did [4, 13, 15].

Vibrio spp. had been reported as the leading causative pathogen of NF and related fatality in our institution, which is located at warm-water coastal regions in southwest Taiwan [6, 15‐18]. Vibrio NF usually occurs through the injuries sustained when handling seafood, wound exposure to seawater, and ingestion of contaminated undercooked seafood [15‐18]. We have established a treatment strategy including emergency fasciotomy or amputation, antibiotic therapy with a third-generation cephalosporin plus tetracycline, and admission to the intensive care unit (ICU) for patients with fulminant necrotizing fasciitis, such as Vibrio, MRSA, and Aeromonas infections [6, 15‐18]. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score has been proposed as a tool to identify patients at a higher risk for NF, in which a LRINEC score of 6 or greater would indicate a high risk for the presence of NF and be widely used [1]. However, our previous study revealed that the LRINEC scoring system is not appropriate for determining early diagnosis with Vibrio NF [6]. Our previous study had demonstrated that the clinical features of Vibrio vulnificus infection were more rapidly progressive and fulminant than those of the MRSA or MSSA infection, but it was a retrospective study [15]. Thus, we conducted this prospective study to search out the association between LRINEC scores and early detection of V. vulnificus and MRSA NF.

The Chiayi Chang Gung Memorial Hospital is a tertiary hospital which situated on the western coast of southern Taiwan, and V. vulnificus are the most frequent causative organism of monomicrobial NF. The residents’ occupations were fishermen or farmers who were frequently associated with handling raw seafood, exposure to seawater, and contact with brackish water or soil [6, 16, 16, 17, 19]. However, Vibrio spp. and Aeromonas spp. infections have a relatively high incidence and associated with high mortality in our institution [6, 15‐17, 19, 20]. We have identified as hypotensive shock, severe hypoalbuminemia, severe thrombocytopenia, and increased banded leukocyte forms can be considered as clinical and laboratory risk indicators to initiate early surgery for Vibrio and all types of necrotizing fasciitis [6, 15‐17, 19‐21]. Moreover, we had established a treatment protocol including emergency fasciotomy or amputation, antibiotic therapy with a third-generation cephalosporin and admission to the intensive care unit for suspected Vibrio NF patients, and had successfully decreased the mortality rate of Vibrio NF from 35 to 13% during the 6-year period from 2004 to 2010 [6, 15‐17, 19, 20]. In this prospective study, we had diminished the mortality rate of total NF to 10.9% and Vibrio NF to 10% respectively after early suspicion and aggressive traeatment by the team works.

Diabetes mellitus has been reported to be a common underlying disease in NF patients, accounting for 44–72% in the literatures [1‐11]. Many literatures had also demostrated that hepatic dysfunction, such as liver cirrhosis, hepatitis B or C, hepatocellular carcinoma, or alcoholic liver disease, was a highly risk factor for developing NF [1‐5, 19, 22‐24]. Those virulence factors of micro-organisms, such as V. vulnificus, S. aureus, β-hemolytic Streptococcus, Aeromonas spp. and P. aeruginosa, were commonly reported to impair the phagocytic activity of the reticuloendothelial system, and to result in bacterial translocation and bacteremia in patients with hepatic decompensation [13‐24]. In this study, we found there were 50.5% of NF patients had associated with a history of hepatic dysfunction, and 40.2% had diabetes mellitus. Most of all, those NF patients with both hepatic dysfunction and diabetes mellitus had a significantly higher mortality. Thus, our finding should alert the clinicans to pay more attention and treat aggressively for those NF patients with a history of hepatic dysfunction and/or diabetes mellitus who may result in fulminant clinical course and mortality in a short time.

Recent literatures have revealed that monomicrobial necrotizing fasciitis caused by Gram-negative pathogens, such as V. vulnificus, Klebsiella pneumoniae, Aeromonas hydrophila, Pseudomonas spp. and Escherichia coli, had persistently increased, and could cause more fulminant clinical courses and higher incidence of mortality rate than Gram-positive pathogens do [19, 25‐31]. Monomicrobial Gram-negative NF combined with bloodstream infection was reported to have significantly increased the mortality rate [25‐31]. This prospective study indicated that the incidence of monomicrobial necrotizing fasciitis (58.7%) was higher than that of polymicrobial infections (12%). Moreover, we found that the monomicrobial Gram-negative NF patients had a greater proportion (55.6% vs. 44.4%) and revealed higher mortality rates (16.7% vs. 6.25%) than the Gram-positive NF patients. Based on those findings, we should pay more attention to manage Gram-negative NF due to its rapid and fulminant courses with increasing risk of developing bacteremia and poor outcomes.

Our previous study had reported that the clinical characteristics of V. vulnificus infection were more rapidly progressive and fulminant than those of the S. aureus infection, either MRSA or MSSA [15]. However, since it was a retrospective study, some medical records of patients did not include accurate descriptions and laboratory data. We conducted this prospective study to investigate the outcomes of early detection and surgery of NF, and the association of the specific characteristics and risk factors on initial examination of V. vulnificus and MRSA NF. We had demonstrated that V. vulnificus NF patients had significant associations with a history of contact with seawater or seafood and MRSA had significant association with a history of diabetes mellitus, previous abrasion injury, pus accumulated in surgical wound, and chronic ulcers [15]. With early diagnosis and emergent surgery, the mortality rates in the patients with V. vulnificus and S. aureus of 18.3% and 13.1% respectively during the 6-year period from 2003 to 2009 were reduced to a mortality rate of 10% and 6.5% respectively during a 3-year period. Moreover, the mortality rate in the patients with MRSA necrotizing fasciitis was reduced from 17.2 to 6.25% [15].

Liver cirrhosis is considered as a risk factor with increasing mortality among NF patient [2‐6, 24, 26, 28, 30]. Seven Vibrio NF patients and 3 MRSA NF patients had liver cirrhosis with/without other chronic illness, and one died respectively in this study. We found that one Vibrio NF patient (14.3%) and 3 MRSA NF patients (100%) with liver cirrhosis had CRP bigger than 150 mg/L and LRINEC score > 6. Thus, we considered the lower CRP and LRINEC score were related to rapidly progressive and fulminant course of V. vulnificus NF, not related to liver cirrhosis.

As a diagnostic tool for severe NF, this prospective study indicated that the application of LRINEC score is species dependent due to the higher score for MRSA group, which may be as a result of longer interval from contact to symptom presentation at ER. We confirmed that the LRINEC scoring system is inappropriate for determining the early diagnosis of Vibrio NF patients who revealed fast and fulminant septic status. Otherwise, V. vulnificus group had significant differences in the clinical characteristics and laboratory data, such as hypotension at emergency room, shorter interval from contact or injury to symptom presentation at ER, presence of bacteremia, thrombocytopenia, and lower CRP level than MRSA group. These results demonstrated V. vulnificus NF revealed more rapidly progressive and fulminant than MRSA NF.

This study has several limitations. First, there was 29.3% of microbial cultures of clinical specimens resulting in negative with the mortality rate of 7.4%. Polymerase chain reaction (PCR) can be considered for early detection and accurate confirmation of the pathogens in sterile sites of these suspicious patients for appropriate antibiotics use. The second limitation was that we did not do LRINEC scoring system for all 184 patients. In fact, our emergency department had reported that the Vibrio vulnificus and Aeromonas hydrophila NF patients had average LRINEC score of 3.9 and 3.5, which were lower than the mean of the whole NF group. Thus, LRINEC score not be an accurate tool for necrotizing fasciitis risk stratification and differentiation in the suburban and tertiary coastal hospital [32].