Scandinavian Journal of Infectious Diseases, 2014; 46: 130–135
ORIGINAL ARTICLE
Skin and soft tissue infection caused by Achromobacter xylosoxidans: report of 14 cases
Scand J Infect Dis Downloaded from informahealthcare.com by Nyu Medical Center on 06/22/15 For personal use only.
DANIEL TENA, NORA MARIELA MARTÍNEZ, CRISTINA LOSA & SONIA SOLÍS From the Sección de Microbiología, Hospital Universitario de Guadalajara, Guadalajara, Spain
Abstract Background: Skin and soft tissue infections (SSTIs) caused by Achromobacter xylosoxidans are very infrequent. The aim of the present study was to investigate the clinical and microbiological characteristics of this infection. Methods: We carried out a retrospective review of 14 cases of SSTI due to A. xylosoxidans that occurred at the University Hospital of Guadalajara (Spain) from January 2007 to December 2012. Results: The infection was secondary to vascular diseases, trauma, and recent surgery in 12 patients (85.7%). The most frequent clinical presentation was infection of a vascular ulcer (5 cases). The infection was monomicrobial in 7 patients (50%) and 9 cases were community-acquired (64.2%). The clinical outcome of the patients was uniformly good after antibiotic treatment, except in 4 patients who suffered recurrence of the infection. Conclusion: A. xylosoxidans should be considered a potential pathogen in patients with SSTIs, especially in patients with vascular diseases or after surgery or trauma. A history of contact with water should be investigated in all cases. Treatment can be difficult due to the high level of antibiotic resistance. Trimethoprim–sulfamethoxazole may be useful for treatment in outpatients with community-acquired infections.
Keywords: Skin infection, soft tissue infection, wound infection, surgical site infection, Achromobacter xylosoxidans, Achromobacter denitrificans, Alcaligenes species
Introduction Achromobacter xylosoxidans (formerly known as Alcaligenes xylosoxidans) is an aerobic, oxidasepositive, catalase-positive, non-fermenting Gramnegative bacillus that inhabits a variety of aquatic environments [1]. A. xylosoxidans was isolated and named in 1971 by Yabuuchi and Oyama, from ear discharges of 7 patients with chronic otitis media [2]. Seven species are currently described within the genus Achromobacter, namely A. xylosoxidans, A. denitrificans, A. insolitus, A. marplatensis, A. piechaudii, A. ruhlandii, and A. spanius [3]. However, species identification is difficult using conventional methods and clinical isolates are generally referred to as A. xylosoxidans. This organism is an opportunistic and emerging pathogen [4]. A. xylosoxidans has been implicated in sporadic infections and outbreaks of nosocomial infections associated with contaminated solutions, pressure transducers, and
contaminated disinfectants [5–8]. Bacteremia, often related to intravascular catheters, is the most commonly reported infection [5]. In the past few years, nosocomial infections have become more evident, especially in patients with hematological neoplasias or solid tumors [9,10]. Skin and soft tissue infections (SSTIs) due to A. xylosoxidans are very unusual. Because of the very limited data available, we analyzed the clinical and microbiological characteristics of 14 cases that occurred in our area over a period of 6 y.
Patients and methods We carried out a retrospective review of all cases of SSTI due to A. xylosoxidans that occurred at the University Hospital of Guadalajara (Spain), a 400-bed teaching hospital, from January 2007 to December 2012. All strains were isolated from
Correspondence: D. Tena, Sección de Microbiología, Hospital Universitario de Guadalajara, C/. Donantes de Sangre s/n, 19002 Guadalajara, Spain. Tel: ⫹34 949 209236. Fax: ⫹34 949 209213. E-mail: [email protected] (Received 21 August 2013 ; accepted 12 October 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.857043
77/M
57/F
82/F
80/F
26/M
75/F
93/F
73/M
47/F
18/M 81/M
42/M 67/F
2
3
4
5
6
7
8
9
10
11 12
13 14
Chronic vascular insufficiency, wound dressings Chronic vascular insufficiency, wound dressings Trauma (traffic accident)
Trauma (agricultural accident) Chronic ischemia with necrosis, treatment with steroids Recent surgery (total knee arthroplasty)
Predisposing factors
Cerebral palsy Arterial hypertension, chronic renal failure, diabetes mellitus, obesity
Pilonidal cyst Osteomyelitis
Arterial hypertension, deep vein thrombosis
No Chronic vascular insufficiency
Recent surgery (submandibular abscess debridement) Recent surgery No
Arterial hypertension, Chronic ischemia diabetes mellitus, osteomyelitis Arterial hypertension, Chronic vascular diabetes mellitus, insufficiency cerebrovascular accident Parkinson disease, obesity, Chronic vascular alcoholism, deep vein insufficiency, trauma thrombosis
Arterial hypertension, obesity, malnutrition, heart failure Diabetes mellitus, ischemic heart disease, chronic renal failure No
No
Arterial hypertension, COPD
No
Underlying diseases
Gluteal abscess Ulcer infection (leg) Whitlow (toe) Infection of vascular ulcer (leg)
Infection of vascular ulcer (foot) Infection of vascular ulcer, cellulitis (leg) Wound infection, cellulitis (foot) Cervical abscess
Wound infection (leg) Infection of necrotic lesion (toe) Surgical wound infection (knee) Infection of vascular ulcer (leg) Infection of vascular ulcer (sacrum) Wound infection (face, neck)
Clinical presentation
aOther
No
Yes (Pseudomonas aeruginosa)
No
No
Yes (Staphylococcus aureus, Streptococcus spp.) Yes (Streptococcus spp.)
No
Yes (Enterococcus spp.)
No
Mixed infectiona
Wou exudate Ulcer exudate
No Yes (Staphylococcus aureus)
Abscess aspirate No Ulcer exudate Yes (Bacteroides spp.)
Abscess aspirate Yes (Candida albicans)
Wound exudate
Ulcer exudate
Ulcer exudate
Wound exudate
Ulcer exudate
Ulcer exudate
Wound exudate
Skin exudate
Wound exudate
Source of isolate
M, male; F, female; COPD, chronic obstructive pulmonary disease; T–S, trimethoprim–sulfamethoxazole. microorganisms isolated are given in parenthesis. bAntibiotic treatment associated with surgical treatment. cNot related with wound infection.
54/M
Age/sex
1
Case No.
Table I. Characteristics of patients with skin and soft tissue infections due to Achromobacter xylosoxidans.
Scand J Infect Dis Downloaded from informahealthcare.com by Nyu Medical Center on 06/22/15 For personal use only.
No No
No No
No
No
No
No
No
Possible
Possible
Unknown
Unknown
Possible
Nosocomially acquired
Diedc
Cured
Cured
Cured
Recurrence
Outcome
Ciprofloxacin Amoxicillin– clavulanic acid, ciprofloxacin
Recurrence Recurrence
Cured Recurrence
Cured
Ciprofloxacinb
T–S Gentamicin
Cured
Diedc
Amoxicillin– clavulanic acidb
Ceftriaxone
Cured Amoxicillin– clavulanic acid ⫹ ciprofloxacinb Cefuroxime Cured
Amoxicillin– clavulanic acid ⫹ levofloxacin T–S
Unknown
Amoxicillin– clavulanic acidb Unknown
Antibiotic treatment
SSTI caused by A. xylosoxidans 131
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cultures of wound or abscess exudates. Identification of the strains was performed using the API 20 NE system (bioMérieux, Marcy l’Etoile, France) and the Vitek II system (bioMérieux, Marcy l’Etoile, France) in accordance with reported techniques [11]. An antibiotic susceptibility study was done using susceptibility cards by Vitek (bioMérieux, Marcy l’Etoile, France), as described previously [11]. We reviewed the clinical charts of all cases. Data obtained from the clinical charts included: age, sex, underlying diseases, predisposing factors (skin disease, trauma, or surgery), clinical presentation, location, source of isolate, mixed infection, type of infection (community-acquired or nosocomial), antibiotic treatment, and outcome. We defined SSTI according to previous guidelines [12]. A. xylosoxidans was judged to be the cause of the SSTI if the sample was correctly obtained, Gram-negative rods were observed by Gram staining associated with the inflammatory response, the organism was the sole or predominant bacterium isolated, and the patient had a clinically significant infection. A. xylosoxidans was considered a colonizer if these conditions were not present; these cases were excluded from the study. Infections that occurred more than 72 h after admission in patients who had no evident infection on admission were categorized as nosocomial [13]. A postoperative infection was defined as nosocomial if the infection was acquired within 30 days after the surgical procedure [14]. A response to therapy was defined as disappearance of all signs and symptoms of infection. Attributable mortality was defined as death within 2 weeks of the last positive A. xylosoxidans wound culture in the absence of other causes of death. Results A. xylosoxidans was isolated from 14 patients with SSTIs. In our area, the frequency of SSTIs due to A. xylosoxidans was 0.23% (proportion of positive cultures). Relevant clinical and microbiological data of the 14 cases are summarized in Table I. The mean age of our patients was 62.2 y (range 18–93 y). Underlying diseases were present in 11 patients (78.5%). The SSTI was secondary to trauma, recent surgery, and vascular diseases in 12 patients (85.7%). The most frequent clinical presentation was infection of a vascular ulcer (5 cases). A. xylosoxidans was the only pathogen isolated from 7 of the 14 specimens (50%). Nine infections were community-acquired (64.2%). The clinical outcome was uniformly good after antibiotic treatment, except in 4 patients who suffered recurrence of the infection. A summary of the susceptibility testing results for the 14 clinical isolates recovered from our patients is presented in Table II.
Table II. Antibiotic susceptibility of Achromobacter xylosoxidans strains.
Antibiotic Ampicillin Amoxicillin–clavulanic acid Cefuroxime Cefotaxime Ceftazidime Piperacillin–tazobactam Imipenem Gentamicin Tobramycina Amikacin Ciprofloxacin Trimethoprim– sulfamethoxazoleb aData bData
Total No. of strains sensitive 1 8 0 1 14 13 11 3 3 4 3 12
Percentage of strains sensitive 7.1% 57.1% 0% 7.1% 100% 92.8% 78.5% 21.4% 25% 28.5% 21.4% 92.3%
available for 12 strains. available for 13 strains.
Discussion A. xylosoxidans is a very uncommon cause of SSTI. To our knowledge, only sporadic cases have been described previously [15–21]. Relevant data of these cases are presented in Table III. The real incidence of SSTIs caused by this organism is unknown. In our area, the frequency of SSTIs due to A. xylosoxidans was 0.23%. This low number of cases suggests that the organism is either not a common part of the normal human flora or is of low virulence. Because of the retrospective nature of our study, it was difficult to determine the source of infection and the mode of transmission. A. xylosoxidans colonizes aquatic environments, especially in hospitals. The organism is not usually found on fomites or in non-aquatic surroundings and may be a part of the ‘hospital flora’ [22]. Eshwara et al. described a wound infection acquired nosocomially from contaminated wound dressings [21], and Vu-Thien et al. reported an outbreak of wound infections transmitted by chlorhexidine in a burns unit [23]. The infection has also been associated with the ingestion of contaminated water [17,18]. This organism should be suspected in patients with wounds who have a history of contact with water or aqueous solutions. A. xylosoxidans has traditionally been recognized as a nosocomial pathogen, but our study shows that this organism may also be considered a community-acquired pathogen, because half of the infections were communityacquired. Most of our patients had underlying diseases. The presence of vascular diseases, trauma, and recent surgery predisposed the patients to the development of the infection. A finding of interest is that 7 of our patients had infections related with a chronic vascular insufficiency or chronic ischemia. These
61/F
46/M
40/M
8 (Legrand and Anaissie, 1992) [19]
9 (Tsay et al., 2005) [20]
10 (Eshwara et al., 2011) [21]
aOther
Clinical presentation
Blood, deep wound exudate, well water Blood, synovial fluid
Wound exudate
Wound exudate
Wound exudate
Wound exudate
Wound exudate
Source of isolate
Systemic lupus erythematous Ingestion of well Bacteremia, water septic arthritis, cellulitis (ankle, knee, wrist) Acute myelogenous leukemia Neutropenia Bacteremia, Blood, skin metastatic culture skin lesions, pneumonia Diabetes mellitus Recent surgery Bacteremia, Blood, wound (decortication wound exudate of empyema) infection Breast carcinoma Recent surgery Wound infection Wound exudate, (mastectomy), dressing contaminated material wound dressings
Surgical wound infection Ingestion of well Bacteremia, water cellulitis (flank)
Recent surgery
Recent surgery Surgical wound (mastectomy) infection Trauma, recent Wound infection surgery (orbit) (plastic surgery) Trauma (contact Superficial with water) wound infection (leg) Recent surgery Surgical wound infection
Predisposing factors
M, male; F, female; ND, no data; T–S, trimethoprim–sulfamethoxazole. microorganisms isolated are given in parenthesis. bNot related to wound infection. cData from blood and synovial fluid cultures.
41/M
Metastatic breast carcinoma, treatment with hydrocortisone
79/F
7 (San Miguel et al., 1991) [18]
ND
43/M
5 (Pien and Higa, 1978) [16] 6 (Spear et al., 1988) [17]
ND
26/M
4 (Pien and Higa, 1978) [16]
Fell in a drain at his home
Breast carcinoma, treatment with steroids Eye shrapnel wound
73/M
36/M
38/F
Underlying diseases
3 (Holmes et al., 1977) [15]
1 (Holmes et al., 1977) [15] 2 (Holmes et al., 1977) [15]
Case No. (author, y) Age/sex
No
No
Yes
Yes
ND
No
Noc
No
No
ND
ND
No
ND
ND
Nosocomially acquired
No
Yes (Pseudomonas aeruginosa, Acinetobacter anitratus) Yes (Candida spp.)
No
No
No
Mixed infectiona
Table III. Characteristics of previously reported patients with skin and soft tissue infections caused by Achromobacter xylosoxidans.
Scand J Infect Dis Downloaded from informahealthcare.com by Nyu Medical Center on 06/22/15 For personal use only.
ND
ND
Cured
ND
ND
Outcome
Cured
Diedb
Levofloxacin ⫹ cefotaxime
Cured
Cefepime
T–S
Diedb Cefuroxime ⫹ tobramycin, T–S ⫹ imipenem ⫹ penicillin Piperacillin, Cure ceftazidime
Gentamicin
Minocycline, gentamicin
No
ND
ND
Antibiotic treatment
SSTI caused by A. xylosoxidans 133
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7 patients were older and 4 of them were diabetics. Diabetes is a recognized cause of vascular disease with a high risk of infection [24]. There appear to be no cases reported in the literature of vascular ulcer infections caused by this organism. The presence of vascular disease should be considered a risk factor for this infection. The clinical manifestations do not differ significantly from those due to other organisms, but the presence of A. xylosoxidans in the wound might lead to invasive infections that could be fatal, especially in patients with cancer [5,9]. Treatment is often difficult due to the high level of antibiotic resistance. As in previous studies [5,9], most of our isolates were susceptible to ceftazidime, piperacillin–tazobactam, and trimethoprim–sulfamethoxazole, but were resistant to amoxicillin–clavulanic acid, cefuroxime, cefotaxime, aminoglycosides, and fluoroquinolones. An important clue to suspect the presence of this organism in clinical specimens is its peculiar antibiogram [22]. However, discrepancies between different automated susceptibility systems have been reported for non-fermenting Gram-negative bacilli [25]. For this reason, susceptibility results using automated systems should be confirmed with additional methods. Currently, carbapenems, antipseudomonal penicillins, and trimethoprim–sulfamethoxazole are considered the agents of choice for the treatment of A. xylosoxidans infections [9]. Synergistic antimicrobial combinations have been investigated due the bacteriostatic nature of some active antibiotics such as trimethoprim–sulfamethoxazole. The combination of trimethoprim–sulfamethoxazole with gentamicin, piperacillin, or azithromycin has been shown to be synergistic [5,26]. Other antimicrobial combinations with synergistic effects include piperacillin plus gentamicin and azithromycin plus doxycycline [5,26]. These favorable antimicrobial combinations may provide treatment alternatives for infections caused by multidrug-resistant A. xylosoxidans strains. The optimal therapeutic regimen for treating A. xylosoxidans SSTIs remains unclear because of the limited data. Trimethoprim–sulfamethoxazole can be administered orally and may be useful for treatment in outpatients with community-acquired infections. The clinical outcome of most of our patients was good after antibiotic treatment. Eight were cured, but the infection was polymicrobial in 3 of them. It is difficult to determine the contribution of this organism to disease in patients with polymicrobial infections. Sometimes A. xylosoxidans coexists with other organisms, and its presence should not be overlooked by considering it a non-pathogen [22]. In this way, 8 of the 10 infections reported previously were monomicrobial [15,17–21]. This finding shows the potential of A. xylosoxidans to cause SSTIs. Four patients
suffered recurrence. The infection was polymicrobial in one of them, and the recurrence was the result of incorrect treatment because A. xylosoxidans was considered a contaminant. In the 3 remaining patients, the strains were susceptible to the antibiotics administered but the patients suffered a new infection. Reasons for these recurrences are unknown. Even when serum concentrations are adequate, therapeutic antimicrobial levels may not be achievable in infected tissues, especially in patients with peripheral vascular disease. Moreover, optimal wound care (debridement, dressing changes, pressure offloading) is needed to avoid recurrence or treatment failure [24]. Further studies should be performed to focus on the optimal therapeutic regimens for treating these infections. In conclusion, the aim of this paper is to alert clinicians to the involvement of A. xylosoxidans in SSTIs. This organism should be considered a potential pathogen, especially in patients with vascular diseases or after surgery or trauma. A history of contact with water should be investigated in all cases. Treatment can be difficult due to the high level of antibiotic resistance. Trimethoprim–sulfamethoxazole may be useful for treatment in outpatients with community-acquired infections. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References [1] Schreckenberger PC, Daneshvar MI, Hollis DG. Acinetobacter, Achromobacter, Chryseobacterium, Moraxella, and other nonfermentative Gram-negative rods. In: Murray PR, Baron JE, Jorgensen JH, Landry ML, Pfaller MA, editors. Manual of clinical microbiology. Washington DC: ASM Press; 2007 pp 770–802. [2] Yabuuchi E, Oyama A. Achromobacter xylosoxidans n. sp. from human ear discharge. Jpn J Microbiol 1971;15:477–81. [3] Ridderberg W, Wang M, Norskov-Lauritsen N. Multilocus sequence analysis of isolates from patients with cystic fibrosis reveals infecting species other than Achromobacter xylosoxidans. J Clin Microbiol 2012;50:2688–94. [4] Igra-Siegman Y, Chmel H, Cobbs C. Clinical and laboratory characteristics of Achromobacter xylosoxidans infection. J Clin Microbiol 1980;11:141–5. [5] Duggan JM, Goldstein SJ, Chenoweth CE, Kauffman CA, Bradley SF. Achromobacter xylosoxidans bacteremia: report of four cases and review of the literature. Clin Infect Dis 1996;23:569–76. [6] Tena D, Carranza R, Barberá JR, Valdezate S, Garrancho JM, Arranz M, et al. Outbreak of long-term intravascular catheter-related bacteremia due to Achromobacter xylosoxidans subspecies xylosoxidans in a hemodialysis unit. Eur J Clin Microbiol Infect Dis 2005;24:727–32. [7] Reina J, Antich M, Siquier B, Alomar P. Nosocomial outbreak of Achromobacter xylosoxidans associated with a diagnostic contrast solution. J Clin Pathol 1988;41:920–3.
Scand J Infect Dis Downloaded from informahealthcare.com by Nyu Medical Center on 06/22/15 For personal use only.
SSTI caused by A. xylosoxidans [8] Gahrn-Hansen B, Alstrup P, Dessau R, Fursted K, Knudsen A, Olsen H, et al. Outbreak of infection with Achromobacter xylosoxidans from contaminated intravascular pressure transducers. J Hosp Infect 1988;12:1–6. [9] Aisenberg G, Rolston KV, Safdar A. Bacteremia caused by Achromobacter and Alcaligenes species in 46 patients with cancer (1989–2003). Cancer 2004;101:2134–40. [10] Shie SS, Huang CT, Leu HS. Characteristics of Achromobacter xylosoxidans bacteremia in northern Taiwan. J Microbiol Immunol Infect 2005;38:277–82. [11] Otto-Karg I, Jandl S, Müller T, Stirzel B, Frosch M, Hebestreit H, et al. Validation of Vitek 2 nonfermenting Gram-negative cards and Vitek 2 version 4.02 software for identification and antimicrobial susceptibility testing of nonfermenting Gram-negative rods from patients with cystic fibrosis. J Clin Microbiol 2009;47:3283–8. [12] Eron LJ, Lipsky BA, Low DE, Nathwabi D, Tice AD, Volturo GA. Managing skin and soft tissue infections: expert panel recommendations on key decision points. J Antimicrob Chemother 2003;52:3–17. [13] Garner JS, Jarvis R, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections. Am J Infect Control 1988;16:128–40. [14] Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection. Infect Control Hosp Epidemiol 1999;20:250–78. [15] Holmes B, Snell JJS, Lapage SP. Strains of Achromobacter xylosoxidans from clinical material. J Clin Pathol 1977; 30:595–601. [16] Pien FD, Higa HY. Achromobacter xylosoxidans isolates in Hawaii. J Clin Microbiol 1978;7:239–41. [17] Spear JB, Fuhrer J, Kirby BD. Achromobacter xylosoxidans (Alcaligenes xylosoxidans subsp. xylosoxidans) bacteremia associated with a well-water source: case report and review of the literature. J Clin Microbiol 1988;26:598–9.
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[18] San Miguel VV, Lavery JP, York JC, Lisse JR. Achromobacter xylosoxidans septic arthritis in a patient with systemic lupus erythematous. Arthritis Rheum 1991;34:1484–5. [19] Legrand C, Anaissie E. Bacteremia due to Achromobacter xylosoxidans in patients with cancer. Clin Infect Dis 1992; 14:479–84. [20] Tsay RW, Lin LC, Chiou CS, Liao JC, Chen CH, Liu CE, et al. Alcaligenes xylosoxidans bacteremia: clinical features and microbiological characteristics of isolates. J Microbiol Immunol Infect 2005;38:194–9. [21] Eshwara VK, Mukhopadhyay C, Mohan S, Prakash R, Pai G. Two unique presentations of Achromobacter xylosoxidans infections in clinical settings. J Infect Dev Ctries 2011;5:138–41. [22] Schoch PE, Cunha BA. Nosocomial Achromobacter xylosoxidans infections. Infect Control Hosp Epidemiol 1988; 9:84–7. [23] Vu-Thien H, Darbord JC, Moissenet D, Dulot C, Dufourcq JB, Marsol P, et al. Investigation of an outbreak of wound infections due to Alcaligenes xylosoxidans transmitted by chlorhexidine in a burn unit. Eur J Clin Microbiol Infect Dis 1998;17:724–6. [24] Lipsky BA. Medical treatment of diabetic foot infections. Clin Infect Dis 2004;39:S104–14. [25] Burns JL, Saiman L, Whittier S, Krzewinski, Liu Z, Larone D, et al. Comparison of two commercial systems (Vitek and MicroScan-WalkAway) for antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis patients. Diagn Microbiol Infect Dis 2001;39:257–60. [26] Saiman L, Chen Y, Gabriel PS, Knirsch C. Synergistic activities of macrolide antibiotics against Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans isolated from patients with cystic fibrosis. Antimicrob Agents Chemother 2002; 46:1105–7.
ORIGINAL ARTICLE
Skin and soft tissue infection caused by Achromobacter xylosoxidans: report of 14 cases
Scand J Infect Dis Downloaded from informahealthcare.com by Nyu Medical Center on 06/22/15 For personal use only.
DANIEL TENA, NORA MARIELA MARTÍNEZ, CRISTINA LOSA & SONIA SOLÍS From the Sección de Microbiología, Hospital Universitario de Guadalajara, Guadalajara, Spain
Abstract Background: Skin and soft tissue infections (SSTIs) caused by Achromobacter xylosoxidans are very infrequent. The aim of the present study was to investigate the clinical and microbiological characteristics of this infection. Methods: We carried out a retrospective review of 14 cases of SSTI due to A. xylosoxidans that occurred at the University Hospital of Guadalajara (Spain) from January 2007 to December 2012. Results: The infection was secondary to vascular diseases, trauma, and recent surgery in 12 patients (85.7%). The most frequent clinical presentation was infection of a vascular ulcer (5 cases). The infection was monomicrobial in 7 patients (50%) and 9 cases were community-acquired (64.2%). The clinical outcome of the patients was uniformly good after antibiotic treatment, except in 4 patients who suffered recurrence of the infection. Conclusion: A. xylosoxidans should be considered a potential pathogen in patients with SSTIs, especially in patients with vascular diseases or after surgery or trauma. A history of contact with water should be investigated in all cases. Treatment can be difficult due to the high level of antibiotic resistance. Trimethoprim–sulfamethoxazole may be useful for treatment in outpatients with community-acquired infections.
Keywords: Skin infection, soft tissue infection, wound infection, surgical site infection, Achromobacter xylosoxidans, Achromobacter denitrificans, Alcaligenes species
Introduction Achromobacter xylosoxidans (formerly known as Alcaligenes xylosoxidans) is an aerobic, oxidasepositive, catalase-positive, non-fermenting Gramnegative bacillus that inhabits a variety of aquatic environments [1]. A. xylosoxidans was isolated and named in 1971 by Yabuuchi and Oyama, from ear discharges of 7 patients with chronic otitis media [2]. Seven species are currently described within the genus Achromobacter, namely A. xylosoxidans, A. denitrificans, A. insolitus, A. marplatensis, A. piechaudii, A. ruhlandii, and A. spanius [3]. However, species identification is difficult using conventional methods and clinical isolates are generally referred to as A. xylosoxidans. This organism is an opportunistic and emerging pathogen [4]. A. xylosoxidans has been implicated in sporadic infections and outbreaks of nosocomial infections associated with contaminated solutions, pressure transducers, and
contaminated disinfectants [5–8]. Bacteremia, often related to intravascular catheters, is the most commonly reported infection [5]. In the past few years, nosocomial infections have become more evident, especially in patients with hematological neoplasias or solid tumors [9,10]. Skin and soft tissue infections (SSTIs) due to A. xylosoxidans are very unusual. Because of the very limited data available, we analyzed the clinical and microbiological characteristics of 14 cases that occurred in our area over a period of 6 y.
Patients and methods We carried out a retrospective review of all cases of SSTI due to A. xylosoxidans that occurred at the University Hospital of Guadalajara (Spain), a 400-bed teaching hospital, from January 2007 to December 2012. All strains were isolated from
Correspondence: D. Tena, Sección de Microbiología, Hospital Universitario de Guadalajara, C/. Donantes de Sangre s/n, 19002 Guadalajara, Spain. Tel: ⫹34 949 209236. Fax: ⫹34 949 209213. E-mail: [email protected] (Received 21 August 2013 ; accepted 12 October 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.857043
77/M
57/F
82/F
80/F
26/M
75/F
93/F
73/M
47/F
18/M 81/M
42/M 67/F
2
3
4
5
6
7
8
9
10
11 12
13 14
Chronic vascular insufficiency, wound dressings Chronic vascular insufficiency, wound dressings Trauma (traffic accident)
Trauma (agricultural accident) Chronic ischemia with necrosis, treatment with steroids Recent surgery (total knee arthroplasty)
Predisposing factors
Cerebral palsy Arterial hypertension, chronic renal failure, diabetes mellitus, obesity
Pilonidal cyst Osteomyelitis
Arterial hypertension, deep vein thrombosis
No Chronic vascular insufficiency
Recent surgery (submandibular abscess debridement) Recent surgery No
Arterial hypertension, Chronic ischemia diabetes mellitus, osteomyelitis Arterial hypertension, Chronic vascular diabetes mellitus, insufficiency cerebrovascular accident Parkinson disease, obesity, Chronic vascular alcoholism, deep vein insufficiency, trauma thrombosis
Arterial hypertension, obesity, malnutrition, heart failure Diabetes mellitus, ischemic heart disease, chronic renal failure No
No
Arterial hypertension, COPD
No
Underlying diseases
Gluteal abscess Ulcer infection (leg) Whitlow (toe) Infection of vascular ulcer (leg)
Infection of vascular ulcer (foot) Infection of vascular ulcer, cellulitis (leg) Wound infection, cellulitis (foot) Cervical abscess
Wound infection (leg) Infection of necrotic lesion (toe) Surgical wound infection (knee) Infection of vascular ulcer (leg) Infection of vascular ulcer (sacrum) Wound infection (face, neck)
Clinical presentation
aOther
No
Yes (Pseudomonas aeruginosa)
No
No
Yes (Staphylococcus aureus, Streptococcus spp.) Yes (Streptococcus spp.)
No
Yes (Enterococcus spp.)
No
Mixed infectiona
Wou exudate Ulcer exudate
No Yes (Staphylococcus aureus)
Abscess aspirate No Ulcer exudate Yes (Bacteroides spp.)
Abscess aspirate Yes (Candida albicans)
Wound exudate
Ulcer exudate
Ulcer exudate
Wound exudate
Ulcer exudate
Ulcer exudate
Wound exudate
Skin exudate
Wound exudate
Source of isolate
M, male; F, female; COPD, chronic obstructive pulmonary disease; T–S, trimethoprim–sulfamethoxazole. microorganisms isolated are given in parenthesis. bAntibiotic treatment associated with surgical treatment. cNot related with wound infection.
54/M
Age/sex
1
Case No.
Table I. Characteristics of patients with skin and soft tissue infections due to Achromobacter xylosoxidans.
Scand J Infect Dis Downloaded from informahealthcare.com by Nyu Medical Center on 06/22/15 For personal use only.
No No
No No
No
No
No
No
No
Possible
Possible
Unknown
Unknown
Possible
Nosocomially acquired
Diedc
Cured
Cured
Cured
Recurrence
Outcome
Ciprofloxacin Amoxicillin– clavulanic acid, ciprofloxacin
Recurrence Recurrence
Cured Recurrence
Cured
Ciprofloxacinb
T–S Gentamicin
Cured
Diedc
Amoxicillin– clavulanic acidb
Ceftriaxone
Cured Amoxicillin– clavulanic acid ⫹ ciprofloxacinb Cefuroxime Cured
Amoxicillin– clavulanic acid ⫹ levofloxacin T–S
Unknown
Amoxicillin– clavulanic acidb Unknown
Antibiotic treatment
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cultures of wound or abscess exudates. Identification of the strains was performed using the API 20 NE system (bioMérieux, Marcy l’Etoile, France) and the Vitek II system (bioMérieux, Marcy l’Etoile, France) in accordance with reported techniques [11]. An antibiotic susceptibility study was done using susceptibility cards by Vitek (bioMérieux, Marcy l’Etoile, France), as described previously [11]. We reviewed the clinical charts of all cases. Data obtained from the clinical charts included: age, sex, underlying diseases, predisposing factors (skin disease, trauma, or surgery), clinical presentation, location, source of isolate, mixed infection, type of infection (community-acquired or nosocomial), antibiotic treatment, and outcome. We defined SSTI according to previous guidelines [12]. A. xylosoxidans was judged to be the cause of the SSTI if the sample was correctly obtained, Gram-negative rods were observed by Gram staining associated with the inflammatory response, the organism was the sole or predominant bacterium isolated, and the patient had a clinically significant infection. A. xylosoxidans was considered a colonizer if these conditions were not present; these cases were excluded from the study. Infections that occurred more than 72 h after admission in patients who had no evident infection on admission were categorized as nosocomial [13]. A postoperative infection was defined as nosocomial if the infection was acquired within 30 days after the surgical procedure [14]. A response to therapy was defined as disappearance of all signs and symptoms of infection. Attributable mortality was defined as death within 2 weeks of the last positive A. xylosoxidans wound culture in the absence of other causes of death. Results A. xylosoxidans was isolated from 14 patients with SSTIs. In our area, the frequency of SSTIs due to A. xylosoxidans was 0.23% (proportion of positive cultures). Relevant clinical and microbiological data of the 14 cases are summarized in Table I. The mean age of our patients was 62.2 y (range 18–93 y). Underlying diseases were present in 11 patients (78.5%). The SSTI was secondary to trauma, recent surgery, and vascular diseases in 12 patients (85.7%). The most frequent clinical presentation was infection of a vascular ulcer (5 cases). A. xylosoxidans was the only pathogen isolated from 7 of the 14 specimens (50%). Nine infections were community-acquired (64.2%). The clinical outcome was uniformly good after antibiotic treatment, except in 4 patients who suffered recurrence of the infection. A summary of the susceptibility testing results for the 14 clinical isolates recovered from our patients is presented in Table II.
Table II. Antibiotic susceptibility of Achromobacter xylosoxidans strains.
Antibiotic Ampicillin Amoxicillin–clavulanic acid Cefuroxime Cefotaxime Ceftazidime Piperacillin–tazobactam Imipenem Gentamicin Tobramycina Amikacin Ciprofloxacin Trimethoprim– sulfamethoxazoleb aData bData
Total No. of strains sensitive 1 8 0 1 14 13 11 3 3 4 3 12
Percentage of strains sensitive 7.1% 57.1% 0% 7.1% 100% 92.8% 78.5% 21.4% 25% 28.5% 21.4% 92.3%
available for 12 strains. available for 13 strains.
Discussion A. xylosoxidans is a very uncommon cause of SSTI. To our knowledge, only sporadic cases have been described previously [15–21]. Relevant data of these cases are presented in Table III. The real incidence of SSTIs caused by this organism is unknown. In our area, the frequency of SSTIs due to A. xylosoxidans was 0.23%. This low number of cases suggests that the organism is either not a common part of the normal human flora or is of low virulence. Because of the retrospective nature of our study, it was difficult to determine the source of infection and the mode of transmission. A. xylosoxidans colonizes aquatic environments, especially in hospitals. The organism is not usually found on fomites or in non-aquatic surroundings and may be a part of the ‘hospital flora’ [22]. Eshwara et al. described a wound infection acquired nosocomially from contaminated wound dressings [21], and Vu-Thien et al. reported an outbreak of wound infections transmitted by chlorhexidine in a burns unit [23]. The infection has also been associated with the ingestion of contaminated water [17,18]. This organism should be suspected in patients with wounds who have a history of contact with water or aqueous solutions. A. xylosoxidans has traditionally been recognized as a nosocomial pathogen, but our study shows that this organism may also be considered a community-acquired pathogen, because half of the infections were communityacquired. Most of our patients had underlying diseases. The presence of vascular diseases, trauma, and recent surgery predisposed the patients to the development of the infection. A finding of interest is that 7 of our patients had infections related with a chronic vascular insufficiency or chronic ischemia. These
61/F
46/M
40/M
8 (Legrand and Anaissie, 1992) [19]
9 (Tsay et al., 2005) [20]
10 (Eshwara et al., 2011) [21]
aOther
Clinical presentation
Blood, deep wound exudate, well water Blood, synovial fluid
Wound exudate
Wound exudate
Wound exudate
Wound exudate
Wound exudate
Source of isolate
Systemic lupus erythematous Ingestion of well Bacteremia, water septic arthritis, cellulitis (ankle, knee, wrist) Acute myelogenous leukemia Neutropenia Bacteremia, Blood, skin metastatic culture skin lesions, pneumonia Diabetes mellitus Recent surgery Bacteremia, Blood, wound (decortication wound exudate of empyema) infection Breast carcinoma Recent surgery Wound infection Wound exudate, (mastectomy), dressing contaminated material wound dressings
Surgical wound infection Ingestion of well Bacteremia, water cellulitis (flank)
Recent surgery
Recent surgery Surgical wound (mastectomy) infection Trauma, recent Wound infection surgery (orbit) (plastic surgery) Trauma (contact Superficial with water) wound infection (leg) Recent surgery Surgical wound infection
Predisposing factors
M, male; F, female; ND, no data; T–S, trimethoprim–sulfamethoxazole. microorganisms isolated are given in parenthesis. bNot related to wound infection. cData from blood and synovial fluid cultures.
41/M
Metastatic breast carcinoma, treatment with hydrocortisone
79/F
7 (San Miguel et al., 1991) [18]
ND
43/M
5 (Pien and Higa, 1978) [16] 6 (Spear et al., 1988) [17]
ND
26/M
4 (Pien and Higa, 1978) [16]
Fell in a drain at his home
Breast carcinoma, treatment with steroids Eye shrapnel wound
73/M
36/M
38/F
Underlying diseases
3 (Holmes et al., 1977) [15]
1 (Holmes et al., 1977) [15] 2 (Holmes et al., 1977) [15]
Case No. (author, y) Age/sex
No
No
Yes
Yes
ND
No
Noc
No
No
ND
ND
No
ND
ND
Nosocomially acquired
No
Yes (Pseudomonas aeruginosa, Acinetobacter anitratus) Yes (Candida spp.)
No
No
No
Mixed infectiona
Table III. Characteristics of previously reported patients with skin and soft tissue infections caused by Achromobacter xylosoxidans.
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ND
ND
Cured
ND
ND
Outcome
Cured
Diedb
Levofloxacin ⫹ cefotaxime
Cured
Cefepime
T–S
Diedb Cefuroxime ⫹ tobramycin, T–S ⫹ imipenem ⫹ penicillin Piperacillin, Cure ceftazidime
Gentamicin
Minocycline, gentamicin
No
ND
ND
Antibiotic treatment
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7 patients were older and 4 of them were diabetics. Diabetes is a recognized cause of vascular disease with a high risk of infection [24]. There appear to be no cases reported in the literature of vascular ulcer infections caused by this organism. The presence of vascular disease should be considered a risk factor for this infection. The clinical manifestations do not differ significantly from those due to other organisms, but the presence of A. xylosoxidans in the wound might lead to invasive infections that could be fatal, especially in patients with cancer [5,9]. Treatment is often difficult due to the high level of antibiotic resistance. As in previous studies [5,9], most of our isolates were susceptible to ceftazidime, piperacillin–tazobactam, and trimethoprim–sulfamethoxazole, but were resistant to amoxicillin–clavulanic acid, cefuroxime, cefotaxime, aminoglycosides, and fluoroquinolones. An important clue to suspect the presence of this organism in clinical specimens is its peculiar antibiogram [22]. However, discrepancies between different automated susceptibility systems have been reported for non-fermenting Gram-negative bacilli [25]. For this reason, susceptibility results using automated systems should be confirmed with additional methods. Currently, carbapenems, antipseudomonal penicillins, and trimethoprim–sulfamethoxazole are considered the agents of choice for the treatment of A. xylosoxidans infections [9]. Synergistic antimicrobial combinations have been investigated due the bacteriostatic nature of some active antibiotics such as trimethoprim–sulfamethoxazole. The combination of trimethoprim–sulfamethoxazole with gentamicin, piperacillin, or azithromycin has been shown to be synergistic [5,26]. Other antimicrobial combinations with synergistic effects include piperacillin plus gentamicin and azithromycin plus doxycycline [5,26]. These favorable antimicrobial combinations may provide treatment alternatives for infections caused by multidrug-resistant A. xylosoxidans strains. The optimal therapeutic regimen for treating A. xylosoxidans SSTIs remains unclear because of the limited data. Trimethoprim–sulfamethoxazole can be administered orally and may be useful for treatment in outpatients with community-acquired infections. The clinical outcome of most of our patients was good after antibiotic treatment. Eight were cured, but the infection was polymicrobial in 3 of them. It is difficult to determine the contribution of this organism to disease in patients with polymicrobial infections. Sometimes A. xylosoxidans coexists with other organisms, and its presence should not be overlooked by considering it a non-pathogen [22]. In this way, 8 of the 10 infections reported previously were monomicrobial [15,17–21]. This finding shows the potential of A. xylosoxidans to cause SSTIs. Four patients
suffered recurrence. The infection was polymicrobial in one of them, and the recurrence was the result of incorrect treatment because A. xylosoxidans was considered a contaminant. In the 3 remaining patients, the strains were susceptible to the antibiotics administered but the patients suffered a new infection. Reasons for these recurrences are unknown. Even when serum concentrations are adequate, therapeutic antimicrobial levels may not be achievable in infected tissues, especially in patients with peripheral vascular disease. Moreover, optimal wound care (debridement, dressing changes, pressure offloading) is needed to avoid recurrence or treatment failure [24]. Further studies should be performed to focus on the optimal therapeutic regimens for treating these infections. In conclusion, the aim of this paper is to alert clinicians to the involvement of A. xylosoxidans in SSTIs. This organism should be considered a potential pathogen, especially in patients with vascular diseases or after surgery or trauma. A history of contact with water should be investigated in all cases. Treatment can be difficult due to the high level of antibiotic resistance. Trimethoprim–sulfamethoxazole may be useful for treatment in outpatients with community-acquired infections. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References [1] Schreckenberger PC, Daneshvar MI, Hollis DG. Acinetobacter, Achromobacter, Chryseobacterium, Moraxella, and other nonfermentative Gram-negative rods. In: Murray PR, Baron JE, Jorgensen JH, Landry ML, Pfaller MA, editors. Manual of clinical microbiology. Washington DC: ASM Press; 2007 pp 770–802. [2] Yabuuchi E, Oyama A. Achromobacter xylosoxidans n. sp. from human ear discharge. Jpn J Microbiol 1971;15:477–81. [3] Ridderberg W, Wang M, Norskov-Lauritsen N. Multilocus sequence analysis of isolates from patients with cystic fibrosis reveals infecting species other than Achromobacter xylosoxidans. J Clin Microbiol 2012;50:2688–94. [4] Igra-Siegman Y, Chmel H, Cobbs C. Clinical and laboratory characteristics of Achromobacter xylosoxidans infection. J Clin Microbiol 1980;11:141–5. [5] Duggan JM, Goldstein SJ, Chenoweth CE, Kauffman CA, Bradley SF. Achromobacter xylosoxidans bacteremia: report of four cases and review of the literature. Clin Infect Dis 1996;23:569–76. [6] Tena D, Carranza R, Barberá JR, Valdezate S, Garrancho JM, Arranz M, et al. Outbreak of long-term intravascular catheter-related bacteremia due to Achromobacter xylosoxidans subspecies xylosoxidans in a hemodialysis unit. Eur J Clin Microbiol Infect Dis 2005;24:727–32. [7] Reina J, Antich M, Siquier B, Alomar P. Nosocomial outbreak of Achromobacter xylosoxidans associated with a diagnostic contrast solution. J Clin Pathol 1988;41:920–3.
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