PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
J Allergy Clin Immunol. Author manuscript; available in PMC 2010 July 1.
Published in final edited form as:
PMCID: PMC2779532
NIHMSID: NIHMS158418

Skin ulcers and disseminated abscesses are characteristic of Serratia marcescens infection in older patients with chronic granulomatous disease

To the Editor:

Chronic Granulomatous Disease (CGD) is a primary immune deficiency resulting from mutations in any of four subunits of phagocytic cell NADPH oxidase. CGD patients are at risk for infections with catalase-positive bacteria and fungi [1-3]. Serratia marcescens infection of bone and soft tissue is a common presentation of CGD in infancy [4-6]. In older children and adults with CGD, infection with Staphylococcus aureus, Burkholderia cepacia and Nocardia species, or fungi such as Aspergillus make up the majority of infections [3,4]. Our experience indicates S. marcescens remains a significant cause of infection in older children and adults with CGD. These infections have a pattern different from that seen in CGD infants. Osteomyelitis is less common, skin infections form poorly healing ulcers [7], and infections frequently occur at multiple sites.

We describe 16 episodes of S. marcescens infections in 15 patients 8–39 years of age with CGD followed between 1999–2008 at the National Institutes of Health (Table 1). Only patients with culture documented S. marcescens were included in this report. All patients were participants in an IRB approved study of the natural history of CGD. Written informed consent specifically allowed study of infections and other complications of CGD.

Table 1
CGD mutation, age at diagnosis of infection, clinical sites of infection and length of antibiotic therapy in patients presenting with S. marcescens infections

Three patients had additional documented S. marcescens infection at some time prior to the index period under review for this report. One of these three patients had a history of two previous S. marcescens lung infections. Each of these prior infections antedate the index review period by at least four years. We did not include these older episodes of infection, as detailed information about those infections was deemed less reliable.

During the review period, some patients had one or more infections characteristic of CGD with organisms other than S. marcescens. Only one (Patient #13, Table 1) developed two episodes of infection with S. marcescens. We conclude that they are distinct Serratia infections and not relapse of the first infection, because those two infections were three years apart. This assumption is consistent with a previous report noting that for most infections in CGD, re-infection is more common than persistent infection [8].

Sites of infection included lung parenchyma (6), vertebrae (1), lymph nodes (3), deep intra-abdominal or pelvic abscess (4), deep soft tissue abscess of limb (6), and superficial infection of skin (2). Seven patients were found to have metastatic infection at multiple sites (Table 1).

None of the 6 patients presenting with pneumonia had clinically apparent secondary sites of S. marcescens infection. Conversely, 7 of the 10 episodes of S. marcescens infection that did not involve pneumonia presented with widely metastatic dissemination. The characteristics of this dissemination included more than one non-contiguous site of skin abscess, deep muscle abscess in limbs and/or abscess in internal organs. A particularly informative example was Patient #9 (Table 1) who presented with skin and soft tissue abscesses (Figure 1). Epididymitis, apparent on physical examination, prompted pelvic Magnetic Resonance Imaging that revealed a prostate abscess (Figure 2).

Figures 1A-C
Photograph of skin ulcers resulting from S. marcescens infection in Patient #9.
Figure 2
Magnetic resonance image of the pelvis of patient #9. The two bright confluent round objects in the center of this image represent a large abscess in the prostate.

Mixed infection in the same biopsy sample (S. aureus or S. anginosis in addition to the Serratia) was identified in four patients, but in all cases the predominant organism by colony count appeared to be S. marcescens. Although the significance and relative impact of these additional organisms on the clinical course was unknown, antibiotic coverage was adjusted as necessary to include coverage for treatment of these additional organisms. In all cases, the S. marcescens isolate was sensitive to a broad range of antibiotic classes including carbapenems, quinolones, cephalosporins, aminoglycosides, extended-spectrum beta-lactams and trimethoprim-sulfamethoxazole. There was a tendency to include or use a quinolone as primary treatment in most cases. If a second antibiotic was used it tended to be either an intravenous carbapenem or intravenous high dose trimethoprim-sulfamethoxazole. In all of the cases these Serratia infections occurred in a setting where standard long term infection prophylaxis had included trimethoprim-sulfamethoxazole. Compliance with this long term prophylaxis was variable. Notably, 10 of 16 of the Serratia isolates were sensitive to this agent. The majority of patients received intravenous antibiotic therapy with two agents for at least a portion of the treatment period. One patient was treated with three intravenous antibiotics and one patient was treated with only one intravenous antibiotic (levofloxacin). Two patients received oral quinolone (ciprofloxacin or levofloxacin) therapy only (lymph node infection in one case and superficial abscess in the other; both without metastatic infection). Duration of therapy varied according to severity of the infection (range 14–180 days; mean 81 days; median 55 days). All infections were successfully eradicated; and all patients survived his or her infection.

Our current report represents the largest aggregate detailed description of Serratia infections in older children and adults with CGD. Previous reports describe either single patients or small case series [4-7], primarily in infants and young children. In other publications, the incidence of Serratia infection is reported incidental to an overall report of a registry of CGD patients without detailed description of the characteristics of the Serratia infections [3]. The important findings of our study reporting the details of 16 episodes of S. marcescens infections in 15 older children and adults with CGD are: 1. Serratia osteomyelitis was uncommon compared to that reported in infants with CGD; 2. Serratia infections of skin form large poorly healing ulcers; 3. Serratia pneumonia in our series was not associated with clinically apparent infection to extrapulmonary sites; 4. Seven of the ten (70%) non-pulmonary infections with Serratia in our series were associated with metastatic spread of infection to multiple sites. As clinically indicated by history, exam or laboratory findings, this group of patients often may require additional imaging studies (CT, MRI or PET scan) to demonstrate the presence of cryptic sites of infection. Finally, we note that all the infections in our series were eventually eradicated; indicating that full recovery from Serratia infection in CGD is an expected outcome with recognition of the variable presentation of this disease and with proper management.

Acknowledgements

The authors were supported in this work by the intramural research program of the National Institute of Allergy and Infectious Diseases and the Center for Cancer Research, National Cancer Institute. No other financial support was received from any other source. All of the authors assert that there is no conflict of interest. The authors wish to acknowledge the assistance of the microbiology service of the Department of Laboratory Medicine and the Department of Radiology at the NIH Clinical Center, as well as the cytology service of the Laboratory of Pathology, National Cancer Institute.

Sources of funding: Funding is only from the intramural programs of the NIAID and NCI, National Institutes of Health. None of the authors has any financial relationships with industries that have an interest in the subject matter or materials discussed in the manuscript.

Footnotes

Key message: Serratia marcescens infections that occur in older children and adults with chronic granulomatous disease have a pattern different from that seen in infants with CGD in that osteomyelitis is much less common; skin infections form large poorly healing ulcers; and infections frequently occur in a metastatic fashion at multiple sites including cryptic internal sites.

References

1. Segal BH, Leto TL, Gallin JI, et al. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine. 2000;79:170–200. [PubMed]
2. Malech HL, Hickstein DD. Genetics, biology and clinical management of myeloid cell primary immune deficiencies: chronic granulomatous disease and leukocyte adhesion deficiency. Curr Opin Hematol. 2007;14:29–36. [PubMed]
3. Winkelstein JA, Marino MC, Johnston RB, Jr, et al. Chronic granulomatous disease: Report on a national registry of 368 patients. Medicine. 2000;79:155–69. [PubMed]
4. Galluzzo ML, Hernandez C, Davila MTG, et al. Clinical and histopathological features and a unique spectrum of organisms significantly associated with chronic granulomatous disease osteomyelitis during childhood. Clin Infect Dis. 2008;46:745–9. [PubMed]
5. Mayer CW, Bangash S, Bocchini JA, et al. Serratia marcescens osteomyelitis in an infant. Allergy Asthma Proc. 2006;27:544–8. [PubMed]
6. Herman TE, Siegel MJ. Chronic granulomatous disease of childhood: Neonatal Serratia hepatic abscesses and pulmonary aspergillosis. J Perinatol. 2002;3:255–6. [PubMed]
7. Soria X, Bielsa I, Ribera M, et al. Acute dermal abscesses caused by Serratia marcescens. J Am Acad Dermatol. 2008;58:891–3. [PubMed]
8. Guide SV, Stock F, Gill VJ, et al. Reinfection, rather than persistent infection in patients with chronic granulomatous disease. J Infect Dis. 2003;187:845–53. [PubMed]