Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitis

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Abstract

Objective. Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy.

Methods. Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75% of nasal swabs.

Results. SA nasal carriage did not change during RTX ( p = 0.297). However, the rate of positive nasal swabs in GPA patients with transient SA nasal carriage during RTX maintenance increased from 0 prior RTX to 0.42 during RTX ( p = 0.017). Persistent SA nasal carriage did not increase the risk of relapses ( p = 0.844), of hypogammaglobulinemia ( p = 0.122) and of severe infections ( p = 0.144), but reduced the risk of chronic infections ( p = 0.044). Change in SA carriage status during RTX did not influence the risk of relapses ( p = 0.756), hypogammaglobulinamia ( p = 0.474) and infections, either severe ( p = 0.913) or chronic ( p = 0.121).

Conclusion. Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not seem to increase the risk of relapses, but seemed to decrease the risk of hypogammaglobulinemia associated chronic infections.

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Most cited references 15

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Reclassification of Staphylococcus aureus nasal carriage types.

Alex van Belkum, Alexander P. N. A. de Porto, J. Verkaik-Kloosterman … (2009)

Persistent nasal carriers have an increased risk of Staphylococcus aureus infection, whereas intermittent carriers and noncarriers share the same low risk. This study was performed to provide additional insight into staphylococcal carriage types. Fifty-one volunteers who had been decolonized with mupirocin treatment and whose carriage state was known were colonized artificially with a mixture of S. aureus strains, and intranasal survival of S. aureus was compared between carriage groups. Antistaphylococcal antibody levels were also compared among 83 carriage-classified volunteers. Persistent carriers preferentially reselected their autologous strain from the inoculum mixture (P=.02). They could be distinguished from intermittent carriers and noncarriers on the basis of the duration of postinoculation carriage (154 vs. 14 and 4 days, respectively; P=.017, by log-rank test). Cultures of swab samples from persistent carriers contained significantly more colony-forming units per sample than did cultures of swab samples from intermittent carriers and noncarriers (P=.004). Analysis of serum samples showed that levels of immunoglobulin G and immunoglobulin A to 17 S. aureus antigens were equal in intermittent carriers and noncarriers but not in persistent carriers. Along with the previously described low risk of infection, intermittent carriers and noncarriers share similar S. aureus nasal elimination kinetics and antistaphylococcal antibody profiles. This implies a paradigm shift; apparently, there are only 2 types of nasal carriers: persistent carriers and others. This knowledge may increase our understanding of susceptibility to S. aureus infection.

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Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis.

W Sluiter, Coen Stegeman, E Haan … (1994)

To examine possible risk factors for relapse, including chronic nasal carriage of Staphylococcus aureus and serial antineutrophil cytoplasmic antibody (ANCA) determinations in patients with Wegener granulomatosis. Observational cohort study. Outpatient clinic at a university-affiliated hospital. Consecutive patients (n = 71) with biopsy-proven Wegener granulomatosis who were seen during follow-up at the outpatient clinic from January 1988 to July 1991. Fourteen patients were ineligible or dropped out; 57 patients were analyzed. Serial ANCA determinations and swab cultures of both anterior nares for S. aureus taken at each visit every 4 to 6 weeks. Occurrence of infections and relapses of Wegener granulomatosis were identified according to strict, predefined criteria. Thirty-six of the 57 patients (63%; 95% CI, 49% to 76%) were found to be chronic nasal carriers of S. aureus (> or = 75% of nasal cultures positive for S. aureus). Proportional-hazards regression analysis identified chronic nasal carriage of S. aureus (adjusted relative risk, 7.16; CI, 1.63 to 31.50), creatinine clearance above 60 mL.min-1 (adjusted relative risk, 2.94; CI, 1.27 to 6.67), and a history of previous relapses of Wegener granulomatosis (adjusted relative risk, 1.33; CI, 0.98 to 1.78) as independent risk factors for relapse. Twenty-two of 33 patients persistently or intermittently positive for ANCA had a relapse as opposed to only 1 of 21 persistently negative patients. Relapses of Wegener granulomatosis were not related to diagnosed infections. Chronic nasal carriage of S. aureus identifies a subgroup of patients with Wegener granulomatosis who are more prone to relapses of the disease, suggesting a role for S. aureus in its pathophysiology and a possible clue for treatment.

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Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group.

Coen Stegeman, Jan Willem Cohen Tervaert, Paul E. de Jong … (1996)

Respiratory tract infections may trigger relapses in patients with Wegener's granulomatosis in remission. Uncontrolled data have suggested that treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) may be beneficial. We conducted a prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole (800 mg of sulfamethoxazole and 160 mg of trimethoprim) given twice daily for 24 months in preventing relapses in patients with Wegener's granulomatosis in remission during or after treatment with cyclophosphamide and prednisolone. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, and histopathological findings. Patients were evaluated at least once every three months for signs of disease activity, compliance with the treatment regimen, side effects of the therapy, and evidence of infections. Titers of serum antineutrophil cytoplasmic antibodies were measured serially. Forty-one patients were assigned to receive co-trimoxazole, and 40 to receive placebo. In 8 of the 41 patients in the co-trimoxazole group (20 percent), the drug had to be stopped because of side effects. According to life-table analysis, 82 percent of the patients remained in remission at 24 months, as compared with 60 percent of the patients in the placebo group (relative risk of relapse, 0.40; 95 percent confidence interval, 0.17 to 0.98). There were fewer respiratory tract infections (P = 0.005) and non-respiratory tract infections (P = 0.05) in the co-trimoxazole group than in the placebo group. There were no significant differences in antineutrophil cytoplasmic antibody titers at any time. Proportional-hazards regression analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free survival and a positive antineutrophil cytoplasmic antibody test at the start of treatment as a risk factor for relapse. Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

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Author and article information

Contributors

Emilio Besada

Journal

Journal ID (nlm-ta): PeerJ

Journal ID (iso-abbrev): PeerJ

Journal ID (pmc): PeerJ

Journal ID (publisher-id): PeerJ

Title: PeerJ

Publisher: PeerJ Inc. (San Francisco, USA )

ISSN (Electronic): 2167-8359

Publication date (Electronic): 25 June 2015

Publication date Collection: 2015

Volume: 3

Electronic Location Identifier: e1051

Affiliations

[1 ]Bone and Joint Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway , Tromsø, Norway

[2 ]Department of Rheumatology, University Hospital of North Norway , Tromsø, Norway

[3 ]School of Medicine and Pharmacology, The University of Western Australia , Crawley, WA, Australia

Article

Publisher ID: 1051

DOI: 10.7717/peerj.1051

PMC ID: 4485735

SO-VID: f62a707c-1b0b-460a-86d9-f2cd2b8d2335

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

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Date received : 31 July 2014

Date accepted : 3 June 2015

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The authors declare there was no funding for this work.

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Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitis

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Most cited references 15

Reclassification of Staphylococcus aureus nasal carriage types.

Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis.

Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group.

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