- Email: [email protected]
Severe soft tissue infections of the extremities in patients admitted to an intensive care unit
Research Note 79
cost is c. 30 euros ⁄ test, and this can be reduced further if the test is performed routinely. High plasma concentrations of b-lactams have neurological toxicity [7]. The mental status of patients receiving high doses of b-lactams has not been investigated thoroughly, and the effects of the very high b-lactam concentrations observed in the present study could be insidious and remain unsuspected. For example, lethargy, asthenia, depression and anorexia are common symptoms in elderly patients treated for endocarditis and are investigated rarely. The main caveat for the systematic monitoring of b-lactam concentrations during treatment of endocarditis is the lack of data on the optimal concentrations required. Although the correlation between very high b-lactam plasma concentrations and toxicity (especially neurological toxicity) is likely, it has not yet been demonstrated formally. Likewise, even though animal models suggest that trough plasma b-lactam concentrations of 4· MIC are sufficient, it is not clear whether these data can be extrapolated to humans. Although there is no reason to increase the trough plasma b-lactam concentrations to > 10· MIC for the treatment of endocarditis (R. Tulkens, personal communication), the results of the present study suggest that the use of current guidelines probably leads to even higher concentrations in most patients, and particularly in the elderly. The consequences of these high concentrations remain to be determined. HPLC could offer an opportunity to monitor plasma b-lactam concentrations, and would allow individualised rather than standardised treatment. Prospective, randomised, multicentre studies are required to evaluate the impact of such monitoring on endocarditis therapy.
2. Craig W. Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens. Eur J Clin Microbiol Infect Dis 1993; 12(suppl 1): S6–S8. 3. Wilson WR, Karchmer AW, Dajani AS et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association. JAMA 1995; 274: 1706–1713. 4. Bayer AS, Bolger AF, Taubert KA et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998; 98: 2936–2948. 5. Hoen B, Alla F, Selton-Suty C et al. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA 2002; 288: 75–81. 6. Dhawan VK. Infective endocarditis in elderly patients. Clin Infect Dis 2002; 34: 806–812. 7. Bloomer HA, Barton LJ, Maddock RK. Penicillin-induced encephalopathy in uremic patients. JAMA 1967; 200: 121– 123. 8. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994; 96: 200–209. 9. Pehourcq F, Jarry C. Determination of third-generation cephalosporins by high-performance liquid chromatography in connection with pharmacokinetic studies. J Chromatogr Anal 1998; 812: 159–178. 10. Cockroft DW, Gault MH. Prediction of creatinine clearance from plasma creatinine. Nephron 1976; 16: 31–41.
RESEARCH NOTE
Severe soft tissue infections of the extremities in patients admitted to an intensive care unit J.-R. Zahar, J. Goveia, P. Lesprit and C. Brun-Buisson Service de Re´animation Me´dicale and d’Immunologie Clinique, Hoˆpital Henri Mondor, Cre´teil, France
ACKNOWLEDGEMENTS This work was presented in part at the 7th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections, Chamonix, France, 2003 and the 14th European Congress of Clinical Microbiology and Infectious Diseases, Prague, Czech Republic, 2004.
ABSTRACT
REFERENCES
Corresponding author and reprint requests: J.-R. Zahar, INSERM U 570, Faculte´ de Me´decine Necker–Enfants Malades, Unite´ de Pathoge´nie des Infections Syste´miques, 156 Avenue de Vaugirard, 75730 Paris cedex 15, France E-mail: [email protected]
1. Cars O. Efficacy of beta-lactam antibiotics: integration of pharmacokinetics and pharmacodynamics. Diagn Microbiol Infect Dis 1997; 27: 29–33.
This report describes a retrospective analysis of 33 patients admitted to an intensive care unit with suspicion of necrotising fasciitis (NF) of the
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 63–82
80 Clinical Microbiology and Infection, Volume 11 Number 1, January 2005
extremities. The aim of the study was to clarify the clinical presentation of NF in order to determine when early surgery should be considered. Twenty-one patients with surgically confirmed NF were compared to 12 patients with superficial soft tissue infection. At admission, patients with NF were more likely to have skin areas of ischaemia or necrosis, fluid-filled vesicles, and severe sepsis or septic shock. Keywords Intensive care unit, necrotising fasciitis, sepsis, soft tissue infection Original Submission: 13 February 2004; Revised Submission: 21 July 2004; Accepted: 3 August 2004
Clin Microbiol Infect 2005; 11: 79–82 10.1111/j.1469-0691.2004.01027.x
Severe skin or soft tissue (SST) infections can involve fascia planes, thereby constituting necrotising fasciitis (NF). Such infections are characterised by extensive necrosis and systemic toxicity [1,2]. Early clinical diagnosis of NF, and differentiation between NF and superficial SST infection (erysipela or cellulitis), may be difficult [3,4]. However, early surgical debridement of patients with NF has been associated with improved survival when compared with delayed surgical exploration [5,6]. The present study describes a retrospective analysis of 33 patients admitted to an intensive care unit (ICU) with severe SST infection of the extremities, with the aim of clarifying the clinical presentation of NF and determining when patients should be referred for early surgery. Data collected included patient demographics, source of infection, predisposing factors, clinical presentation, laboratory parameters, bacteriological findings, management, duration of ICU and hospital stay, and rate of survival. The severity of sepsis at presentation was assessed according to published guidelines and definitions [7], and the severity of acute illness was assessed with the Simplified Acute Physiology Score II (SAPS II) [8]. NF was defined as a soft tissue infection with fascia involvement confirmed at surgery, while superficial SST infection (or ‘medical’ infection) was defined as either (1) soft tissue infection without fascia involvement, as confirmed by surgical exploration, or (2) soft tissue infection that resolved without surgery. In order to examine features associated with NF cases needing
surgical debridement, patients with medical SST infections were compared to patients with confirmed NF. The data were compared by means of the Mann–Whitney U-test. In total, 25 (76%) patients underwent surgical exploration. The mean delay between diagnosis and surgery was 3.4 days (range 0–23 days); 18 patients had surgery within 48 h of diagnosis. At surgery, NF was confirmed in 21 (84%) of these patients, while four patients were diagnosed with superficial SST infection. Twenty-one patients were referred for primary therapy, including 16 who failed to improve after initial therapy. Four patients presented with severe sepsis and 11 with septic shock. The mean age of the patients was 59 years (range 20–88 years). A medical condition predisposing to soft tissue infection was noted in 21 (64%) patients, namely diabetes mellitus (n = 11), cancer (n = 4; all receiving chemotherapy), corticosteroid therapy (n = 8; all receiving > 1 mg ⁄ kg ⁄ day prednisone equivalent) and liver cirrhosis (n = 4); four patients had received non-steroidal anti-inflammatory drugs. A precipitating factor was recorded for 24 (73%) patients, in that 11 patients had a preexisting local infection and 13 patients had a recent history of trauma. The latter group included minor or major limb injury (n = 8), intramuscular injections (n = 4) or surgical amputation (n = 1). Seven cases of infection were hospital-acquired after liposuction surgery (n = 1), bedsore infection (n = 2), infected haematoma while receiving anticoagulant therapy (n = 1), leg ischaemia (n = 1) or surgical wound infection (n = 2). Physical findings are detailed in Table 1. NF was associated significantly with cyanosis, necrotic skin areas, and fluid-filled vesicles. The mean SAPS II on admission was 34.5 (range 10– 96). Patients with NF presented frequently with severe sepsis or shock (n = 15; 71%), whereas there were no such cases among patients with medical SST infection (p 0.0003). There was no difference in laboratory test parameters between the two groups (Table 1). Microbiological findings are detailed in Table 2. Staphylococcus and Streptococus spp. were the most common isolates (Table 2). No microbial pathogen was isolated from 12 patients. Microorganisms were recovered more frequently from patients with NF (86% vs. 25%; p 0.001). Blood cultures were positive for 15 patients, of whom ten also had positive tissue or fluid culture
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 63–82
Research Note 81
Table 1. Clinical characteristics of 33 patients with necrotising fasciitis and severe skin or soft tissue infection
Variables
All patients
Necrotising fasciitis n = 21
Age, years (mean) Temperature (mean) SAPS II (mean) DIC (no. of patients) Clinical presentation Crepitus Necrosis Ischaemia Cyanosis Fluid-filled vesicles Pain Erythema Immunodepression Biological findings Leukocyte count Fibrin CPK C-reactive protein Platelets Severe sepsis or shock at admission (no. of patients) Mechanical ventilation Renal replacement therapy Vasopressive drugs Adequate antibiotic therapy within 48 h Survivors
58.8 ± 16.9 38.1 ± 1.2 36.5 ± 22 6
61.5 ± 15.4 38.2 ± 1.3 36.9 ± 21 5
9 18 11 14 16 27 26 21 12.5 ± 6.4 ± 2008 ± 252 ± 226 ± 15
Superficial SST infection n = 12
p
54.6 ± 19.1 37.8 ± 1.3 31.2 ± 16 1
0.4 0.42 0.5 0.3
7 16 10 12 14 17 17 14 7.9 3 5241 147 160
12.9 ± 5.5 ± 2819 ± 291 ± 203 ± 15
2 2 1 2 2 10 9 7 7.7 2.7 6243 101 154
11.9 ± 6.7 ± 304.5 ± 240 ± 238 ± 0
0.5 0.003 0.1 0.02 0.01 0.6 0.6 0.4 8.5 3.1 439.6 161 165
0.7 0.3 0.2 0.6 0.6 < 0.001
18 7
16 7
2 0
0.003 0.03
12 30
11 19
1 11
0.02 1
11
12
0.005
CPK, creatine phosphokinase; DIC, disseminated intravascular coagulation; SAPS II, Simplified Acute Physiology Score II; SST, skin or soft tissue.
Table 2. Microbiological data for 21 cases of soft tissue infection Pathogens Microbiological data Organism(s) isolated Bacteraemia Monomicrobial ⁄ polymicrobial Gram-negative bacilli Gram-positive cocci Gram-negative bacilli Escherichia coli Klebsiella pneumoniae Citrobacter freundii Pseudomonas aeruginosa Proteus mirabilis Morganellla morganii Gram-positive cocci Staphylococcus aureus Streptococcus pyogenes Streptococcus spp.
Medical SST infection
NF
3 3 3⁄0 0 3
18 12 15 ⁄ 3 8 12 2 2 1 1 1 1
2 0 1
7 3 2
Total no. of isolates
8 2 2 1 1 1 1 15 9 3 3
NF, necrotising fasciitis; SST, skin or soft tissue.
results. For six patients, only tissue or fluid culture results were positive. NF was associated more frequently with bacteraemia (57%) than was superficial SST infection (25%; p 0.009). Empirical antibiotics were administered to all patients, of whom nine received a single antibiotic, 14 received a combination of two antibiotics, and ten received a combination of three or more
antibiotics. The antibiotics used were b-lactams (26 patients), aminoglycosides (18), third-generation cephalosporins (seven), metronidazole (ten), clindamycin (two), and other miscellaneous antibiotics (five). The overall mortality rate was 33%. The mean length of stay in the ICU was 10.6 days (range 1–49 days). There were no deaths in the ‘medical’ group, whereas 52% of patients with NF died (Table 1). Controversies persist over the classification of severe SST infections [9,10]. However, a pragmatic clinical–anatomical classification [3] is used most commonly, based on the different anatomical planes involved and the causative disease. On comparison of patients with NF confirmed at surgery to those who progressed favourably with medical therapy only, it was found that the former were much more likely to have severe sepsis or shock. None of the patients with medical severe SST infection presented with shock, despite a similar SAPS II assessment (Table 2). Therefore, the results suggest that patients presenting with septic shock should undergo rapid surgical exploration, together with resuscitation. Indeed, systemic symptoms are an indication that a necrotising infection has already spread across a large surface area and has disseminated toxins [11,12]. The present study also confirmed previous observations [13–15] that patients with NF present more frequently with cyanosis, skin necrosis and fluid-filled vesicles. However, the specificity of these findings was not 100%, and a few patients with severe medical SST infection presented with such signs (Table 2). Microbiological findings also differed between patients with NF and those with medical SST. Bacteraemia was much more common in patients with NF (57% vs. 25%), often in association with severe sepsis and septic shock. Polymicrobial infection was recorded rarely in this series of patients, which included only SST infection of the extremities, and was not more frequent in patients with NF. Indeed, severe SST infection of the limbs is more often monomicrobial, with the involvement of skin flora [16]. NF is a rare but serious bacterial disease that is often underestimated and poorly recognised [17]. Of the 21 cases in this study, only nine were suspected by the referring or admitting physician, and diagnosis was delayed by 2–10 days following the onset of symptoms. A high index of suspicion is mandatory for an early diagnosis,
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 63–82
82 Clinical Microbiology and Infection, Volume 11 Number 1, January 2005
since early and adequate surgical debridement and fasciotomy has been associated with improved survival compared to delayed surgical intervention [13,18]. The present study had several limitations, including its retrospective design and the small number of patients; however, it was possible to identify four clinical factors and one microbiological factor that were associated significantly with NF in patients admitted to an ICU with severe SST infection. The presence of these signs should prompt early surgical exploration.
8.
9.
10.
11. 12.
REFERENCES 1. Weinbren MJ, Perinpanayagam RM. Streptococcal necrotising fasciitis. J Infect 1992; 25: 299–302. 2. Donaldson PM, Naylor B, Lowe JW, Gouldesbrough DR. Rapidly fatal necrotising fasciitis caused by Streptococcus pyogenes. J Clin Pathol 1993; 46: 617–620. 3. Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med 1996; 334: 240–245. 4. Barker FG, Leppard BJ, Seal DV. Streptococcal necrotising fasciitis: comparison between histological and clinical features. J Clin Pathol 1987; 40: 335–341. 5. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg 1995; 221: 558–563. 6. Majeski JA, Alexander JW. Early diagnosis, nutritional support, and immediate extensive debridement improve survival in necrotizing fasciitis. Am J Surg 1983; 145: 784– 787. 7. Anonymous. ACCP-SCCM Consensus Conference definitions for sepsis and organ failure and guidelines for the
13.
14.
15.
16. 17.
18.
use of innovative therapies in sepsis. Chest 1992; 101: 1644– 1655. Le Gall JR, Lemeshow S, Saulnier F. A new simplified acute physiology score (SAPS II) based on European ⁄ North American multicentre study. JAMA 1993; 270: 2957–2963. Simmons RL, Ahrenholz DH. Infections of the skin and soft tissues. In: Howard RJ, Simmons RL, eds. Surgical infectious diseases. Norwalk: Appleton & Lange, 1988; 404– 408. Umbert IJ, Winkelmann RK, Oliver GL et al. Necrotizing fasciitis: a clinical, microbiologic, and histopathologic study of 14 patients. J Am Acad Dermatol 1989; 20: 774–781. Stevens DL. Invasive group A streptococcal infections. Clin Infect Dis 1992; 14: 2–13. Stevens DL. Streptococcal toxic shock syndrome: spectrum of diseases, pathogenesis, and new concept in treatment. Emerg Infect Dis 1995; 1: 69–78. Elliott DC, Kufera JA, Myers RA. Necrotizing soft tissue infections. Risk factors for mortality and strategies for management. Ann Surg 1996; 224: 672–683. Ward RG, Walsh MD. Necrotizing fasciitis: 10 years’ experience in a district general hospital. Br J Surg 1991; 78: 488–489. Callahan TE, Schecter WP, Horn JK. Necrotizing soft tissue infection masquerading as cutaneous abscess following illicit drug injection. Arch Surg 1998; 133: 812–817. Green RJ, Dafoe DC, Raffin TA. Necrotizing fasciitis. Chest 1996; 110: 219–229. Rangaswamy M. Necrotizing fasciitis: a 10-year retrospective study of cases in a single university hospital in Oman. Acta Trop 2001; 80: 169–175. McHenry CR, Piotrowski JJ, Petrinic D et al. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg 1995; 221: 558–565.
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 63–82
cost is c. 30 euros ⁄ test, and this can be reduced further if the test is performed routinely. High plasma concentrations of b-lactams have neurological toxicity [7]. The mental status of patients receiving high doses of b-lactams has not been investigated thoroughly, and the effects of the very high b-lactam concentrations observed in the present study could be insidious and remain unsuspected. For example, lethargy, asthenia, depression and anorexia are common symptoms in elderly patients treated for endocarditis and are investigated rarely. The main caveat for the systematic monitoring of b-lactam concentrations during treatment of endocarditis is the lack of data on the optimal concentrations required. Although the correlation between very high b-lactam plasma concentrations and toxicity (especially neurological toxicity) is likely, it has not yet been demonstrated formally. Likewise, even though animal models suggest that trough plasma b-lactam concentrations of 4· MIC are sufficient, it is not clear whether these data can be extrapolated to humans. Although there is no reason to increase the trough plasma b-lactam concentrations to > 10· MIC for the treatment of endocarditis (R. Tulkens, personal communication), the results of the present study suggest that the use of current guidelines probably leads to even higher concentrations in most patients, and particularly in the elderly. The consequences of these high concentrations remain to be determined. HPLC could offer an opportunity to monitor plasma b-lactam concentrations, and would allow individualised rather than standardised treatment. Prospective, randomised, multicentre studies are required to evaluate the impact of such monitoring on endocarditis therapy.
2. Craig W. Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens. Eur J Clin Microbiol Infect Dis 1993; 12(suppl 1): S6–S8. 3. Wilson WR, Karchmer AW, Dajani AS et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association. JAMA 1995; 274: 1706–1713. 4. Bayer AS, Bolger AF, Taubert KA et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998; 98: 2936–2948. 5. Hoen B, Alla F, Selton-Suty C et al. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA 2002; 288: 75–81. 6. Dhawan VK. Infective endocarditis in elderly patients. Clin Infect Dis 2002; 34: 806–812. 7. Bloomer HA, Barton LJ, Maddock RK. Penicillin-induced encephalopathy in uremic patients. JAMA 1967; 200: 121– 123. 8. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994; 96: 200–209. 9. Pehourcq F, Jarry C. Determination of third-generation cephalosporins by high-performance liquid chromatography in connection with pharmacokinetic studies. J Chromatogr Anal 1998; 812: 159–178. 10. Cockroft DW, Gault MH. Prediction of creatinine clearance from plasma creatinine. Nephron 1976; 16: 31–41.
RESEARCH NOTE
Severe soft tissue infections of the extremities in patients admitted to an intensive care unit J.-R. Zahar, J. Goveia, P. Lesprit and C. Brun-Buisson Service de Re´animation Me´dicale and d’Immunologie Clinique, Hoˆpital Henri Mondor, Cre´teil, France
ACKNOWLEDGEMENTS This work was presented in part at the 7th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections, Chamonix, France, 2003 and the 14th European Congress of Clinical Microbiology and Infectious Diseases, Prague, Czech Republic, 2004.
ABSTRACT
REFERENCES
Corresponding author and reprint requests: J.-R. Zahar, INSERM U 570, Faculte´ de Me´decine Necker–Enfants Malades, Unite´ de Pathoge´nie des Infections Syste´miques, 156 Avenue de Vaugirard, 75730 Paris cedex 15, France E-mail: [email protected]
1. Cars O. Efficacy of beta-lactam antibiotics: integration of pharmacokinetics and pharmacodynamics. Diagn Microbiol Infect Dis 1997; 27: 29–33.
This report describes a retrospective analysis of 33 patients admitted to an intensive care unit with suspicion of necrotising fasciitis (NF) of the
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 63–82
80 Clinical Microbiology and Infection, Volume 11 Number 1, January 2005
extremities. The aim of the study was to clarify the clinical presentation of NF in order to determine when early surgery should be considered. Twenty-one patients with surgically confirmed NF were compared to 12 patients with superficial soft tissue infection. At admission, patients with NF were more likely to have skin areas of ischaemia or necrosis, fluid-filled vesicles, and severe sepsis or septic shock. Keywords Intensive care unit, necrotising fasciitis, sepsis, soft tissue infection Original Submission: 13 February 2004; Revised Submission: 21 July 2004; Accepted: 3 August 2004
Clin Microbiol Infect 2005; 11: 79–82 10.1111/j.1469-0691.2004.01027.x
Severe skin or soft tissue (SST) infections can involve fascia planes, thereby constituting necrotising fasciitis (NF). Such infections are characterised by extensive necrosis and systemic toxicity [1,2]. Early clinical diagnosis of NF, and differentiation between NF and superficial SST infection (erysipela or cellulitis), may be difficult [3,4]. However, early surgical debridement of patients with NF has been associated with improved survival when compared with delayed surgical exploration [5,6]. The present study describes a retrospective analysis of 33 patients admitted to an intensive care unit (ICU) with severe SST infection of the extremities, with the aim of clarifying the clinical presentation of NF and determining when patients should be referred for early surgery. Data collected included patient demographics, source of infection, predisposing factors, clinical presentation, laboratory parameters, bacteriological findings, management, duration of ICU and hospital stay, and rate of survival. The severity of sepsis at presentation was assessed according to published guidelines and definitions [7], and the severity of acute illness was assessed with the Simplified Acute Physiology Score II (SAPS II) [8]. NF was defined as a soft tissue infection with fascia involvement confirmed at surgery, while superficial SST infection (or ‘medical’ infection) was defined as either (1) soft tissue infection without fascia involvement, as confirmed by surgical exploration, or (2) soft tissue infection that resolved without surgery. In order to examine features associated with NF cases needing
surgical debridement, patients with medical SST infections were compared to patients with confirmed NF. The data were compared by means of the Mann–Whitney U-test. In total, 25 (76%) patients underwent surgical exploration. The mean delay between diagnosis and surgery was 3.4 days (range 0–23 days); 18 patients had surgery within 48 h of diagnosis. At surgery, NF was confirmed in 21 (84%) of these patients, while four patients were diagnosed with superficial SST infection. Twenty-one patients were referred for primary therapy, including 16 who failed to improve after initial therapy. Four patients presented with severe sepsis and 11 with septic shock. The mean age of the patients was 59 years (range 20–88 years). A medical condition predisposing to soft tissue infection was noted in 21 (64%) patients, namely diabetes mellitus (n = 11), cancer (n = 4; all receiving chemotherapy), corticosteroid therapy (n = 8; all receiving > 1 mg ⁄ kg ⁄ day prednisone equivalent) and liver cirrhosis (n = 4); four patients had received non-steroidal anti-inflammatory drugs. A precipitating factor was recorded for 24 (73%) patients, in that 11 patients had a preexisting local infection and 13 patients had a recent history of trauma. The latter group included minor or major limb injury (n = 8), intramuscular injections (n = 4) or surgical amputation (n = 1). Seven cases of infection were hospital-acquired after liposuction surgery (n = 1), bedsore infection (n = 2), infected haematoma while receiving anticoagulant therapy (n = 1), leg ischaemia (n = 1) or surgical wound infection (n = 2). Physical findings are detailed in Table 1. NF was associated significantly with cyanosis, necrotic skin areas, and fluid-filled vesicles. The mean SAPS II on admission was 34.5 (range 10– 96). Patients with NF presented frequently with severe sepsis or shock (n = 15; 71%), whereas there were no such cases among patients with medical SST infection (p 0.0003). There was no difference in laboratory test parameters between the two groups (Table 1). Microbiological findings are detailed in Table 2. Staphylococcus and Streptococus spp. were the most common isolates (Table 2). No microbial pathogen was isolated from 12 patients. Microorganisms were recovered more frequently from patients with NF (86% vs. 25%; p 0.001). Blood cultures were positive for 15 patients, of whom ten also had positive tissue or fluid culture
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 63–82
Research Note 81
Table 1. Clinical characteristics of 33 patients with necrotising fasciitis and severe skin or soft tissue infection
Variables
All patients
Necrotising fasciitis n = 21
Age, years (mean) Temperature (mean) SAPS II (mean) DIC (no. of patients) Clinical presentation Crepitus Necrosis Ischaemia Cyanosis Fluid-filled vesicles Pain Erythema Immunodepression Biological findings Leukocyte count Fibrin CPK C-reactive protein Platelets Severe sepsis or shock at admission (no. of patients) Mechanical ventilation Renal replacement therapy Vasopressive drugs Adequate antibiotic therapy within 48 h Survivors
58.8 ± 16.9 38.1 ± 1.2 36.5 ± 22 6
61.5 ± 15.4 38.2 ± 1.3 36.9 ± 21 5
9 18 11 14 16 27 26 21 12.5 ± 6.4 ± 2008 ± 252 ± 226 ± 15
Superficial SST infection n = 12
p
54.6 ± 19.1 37.8 ± 1.3 31.2 ± 16 1
0.4 0.42 0.5 0.3
7 16 10 12 14 17 17 14 7.9 3 5241 147 160
12.9 ± 5.5 ± 2819 ± 291 ± 203 ± 15
2 2 1 2 2 10 9 7 7.7 2.7 6243 101 154
11.9 ± 6.7 ± 304.5 ± 240 ± 238 ± 0
0.5 0.003 0.1 0.02 0.01 0.6 0.6 0.4 8.5 3.1 439.6 161 165
0.7 0.3 0.2 0.6 0.6 < 0.001
18 7
16 7
2 0
0.003 0.03
12 30
11 19
1 11
0.02 1
11
12
0.005
CPK, creatine phosphokinase; DIC, disseminated intravascular coagulation; SAPS II, Simplified Acute Physiology Score II; SST, skin or soft tissue.
Table 2. Microbiological data for 21 cases of soft tissue infection Pathogens Microbiological data Organism(s) isolated Bacteraemia Monomicrobial ⁄ polymicrobial Gram-negative bacilli Gram-positive cocci Gram-negative bacilli Escherichia coli Klebsiella pneumoniae Citrobacter freundii Pseudomonas aeruginosa Proteus mirabilis Morganellla morganii Gram-positive cocci Staphylococcus aureus Streptococcus pyogenes Streptococcus spp.
Medical SST infection
NF
3 3 3⁄0 0 3
18 12 15 ⁄ 3 8 12 2 2 1 1 1 1
2 0 1
7 3 2
Total no. of isolates
8 2 2 1 1 1 1 15 9 3 3
NF, necrotising fasciitis; SST, skin or soft tissue.
results. For six patients, only tissue or fluid culture results were positive. NF was associated more frequently with bacteraemia (57%) than was superficial SST infection (25%; p 0.009). Empirical antibiotics were administered to all patients, of whom nine received a single antibiotic, 14 received a combination of two antibiotics, and ten received a combination of three or more
antibiotics. The antibiotics used were b-lactams (26 patients), aminoglycosides (18), third-generation cephalosporins (seven), metronidazole (ten), clindamycin (two), and other miscellaneous antibiotics (five). The overall mortality rate was 33%. The mean length of stay in the ICU was 10.6 days (range 1–49 days). There were no deaths in the ‘medical’ group, whereas 52% of patients with NF died (Table 1). Controversies persist over the classification of severe SST infections [9,10]. However, a pragmatic clinical–anatomical classification [3] is used most commonly, based on the different anatomical planes involved and the causative disease. On comparison of patients with NF confirmed at surgery to those who progressed favourably with medical therapy only, it was found that the former were much more likely to have severe sepsis or shock. None of the patients with medical severe SST infection presented with shock, despite a similar SAPS II assessment (Table 2). Therefore, the results suggest that patients presenting with septic shock should undergo rapid surgical exploration, together with resuscitation. Indeed, systemic symptoms are an indication that a necrotising infection has already spread across a large surface area and has disseminated toxins [11,12]. The present study also confirmed previous observations [13–15] that patients with NF present more frequently with cyanosis, skin necrosis and fluid-filled vesicles. However, the specificity of these findings was not 100%, and a few patients with severe medical SST infection presented with such signs (Table 2). Microbiological findings also differed between patients with NF and those with medical SST. Bacteraemia was much more common in patients with NF (57% vs. 25%), often in association with severe sepsis and septic shock. Polymicrobial infection was recorded rarely in this series of patients, which included only SST infection of the extremities, and was not more frequent in patients with NF. Indeed, severe SST infection of the limbs is more often monomicrobial, with the involvement of skin flora [16]. NF is a rare but serious bacterial disease that is often underestimated and poorly recognised [17]. Of the 21 cases in this study, only nine were suspected by the referring or admitting physician, and diagnosis was delayed by 2–10 days following the onset of symptoms. A high index of suspicion is mandatory for an early diagnosis,
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 63–82
82 Clinical Microbiology and Infection, Volume 11 Number 1, January 2005
since early and adequate surgical debridement and fasciotomy has been associated with improved survival compared to delayed surgical intervention [13,18]. The present study had several limitations, including its retrospective design and the small number of patients; however, it was possible to identify four clinical factors and one microbiological factor that were associated significantly with NF in patients admitted to an ICU with severe SST infection. The presence of these signs should prompt early surgical exploration.
8.
9.
10.
11. 12.
REFERENCES 1. Weinbren MJ, Perinpanayagam RM. Streptococcal necrotising fasciitis. J Infect 1992; 25: 299–302. 2. Donaldson PM, Naylor B, Lowe JW, Gouldesbrough DR. Rapidly fatal necrotising fasciitis caused by Streptococcus pyogenes. J Clin Pathol 1993; 46: 617–620. 3. Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med 1996; 334: 240–245. 4. Barker FG, Leppard BJ, Seal DV. Streptococcal necrotising fasciitis: comparison between histological and clinical features. J Clin Pathol 1987; 40: 335–341. 5. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg 1995; 221: 558–563. 6. Majeski JA, Alexander JW. Early diagnosis, nutritional support, and immediate extensive debridement improve survival in necrotizing fasciitis. Am J Surg 1983; 145: 784– 787. 7. Anonymous. ACCP-SCCM Consensus Conference definitions for sepsis and organ failure and guidelines for the
13.
14.
15.
16. 17.
18.
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