Letters to the Editor cellulitis in five years. Clinical risk factors and the role of PTX3 and CRP”.1 They have evaluated the predictive value of pentraxin 3 (PTX3) and C-reactive protein (CRP) upon recurrence of cellulitis then they have concluded that both biomarkers in the acute phase of acute cellulitis did not predict further recurrences. However, there are some points that need to be clarified. PTX3 is an acute phase protein and produced in response to inflammatory conditions in vivo.2 There are several conditions which likely affect PTX3 levels. The authors did not express any exclusion criteria. PTX3 levels vary in several inflammatory or infectious diseases such as rheumatologic diseases, vasculitis, chronic kidney diseases, immunological disorders, pneumonia, chronic obstructive pulmonary disease, asthma, and ulcerative colitis.3,4 In this respect, simple laboratory tests such as complete blood count, routine biochemistry tests and erythrocyte sedimentation rate were assigned in addition to PTX3 and CRP; a robust study group could be designed. Previous studies suggested that glucocorticoids, angiotensin converting enzyme inhibitors, and statins could alter serum PTX3 levels.5 Also, dietary food supplements such as vitamin D, omega-3 fatty acid, vitamin A, and vitamin E could influence PTX3 levels.6 Therefore, supplement usage should be examined to provide reliable findings. In conclusion, the explanation of above concerns will certainly provide the clearer information for the readers.

Conflict of interest

547 Fevzi Nuri Aydin Department of Biochemistry, Sirnak Military Hospital, Sirnak, Turkey *Corresponding author. Tel.: þ90 505 682 98 19; fax: þ90 472 215 27 47.

E-mail address: [email protected] Accepted 4 January 2015 http://dx.doi.org/10.1016/j.jinf.2015.01.002 DOI of original article: http://dx.doi.org/10.1016/j.jinf.2014.11. 002 ª 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Response to Agilli and Aydin

KEYWORDS Pentraxin; C-reactive protein; Recurrent cellulitis; Risk factor

The authors declare that there is no conflict of interest.

References 1. Karppelin M, Siljander T, Aittoniemi J, Hurme M, Huttunen R, Huhtala H, et al. Predictors of recurrent cellulitis in five years. Clinical risk factors and the role of PTX3 and CRP. J Infect 2014. http://dx.doi.org/10.1016/j.jinf.2014.11.002. 2. Yaman H, Cakir E, Akgul EO, Aydin I, Onguru O, Cayci T, et al. Pentraxin 3 as a potential biomarker of acetaminopheninduced liver injury. Exp Toxicol Pathol 2013;65:147e51. 3. Bonacina F, Baragetti A, Catapano AL, Norata GD. Long pentraxin 3: experimental and clinical relevance in cardiovascular diseases. Mediators Inflamm 2013;2013:725102. 4. Agilli M, Aydin FN, Cayci T, Kurt YG. Pentraxin 3 (PTX3) plasma levels and carotid intima media thickness progression in the general population: a methodological approach. Nutr Metab Cardiovasc Dis 2014;24:e38e9. 5. Iwata A, Miura S, Tanaka T, Ike A, Sugihara M, Nishikawa H, et al. Plasma pentraxin-3 levels are associated with coronary plaque vulnerability and are decreased by statin. Coron Artery Dis 2012;23:315e21. 6. Rosjo E, Myhr KM, Loken-Amsrud KI, Bakke SJ, Beiske AG, Bjerve KS, et al. Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis. J Neuroimmunol 2014;271:60e5.

Mehmet Agilli* Department of Biochemistry, Agri Military Hospital, Agri, Turkey

Sir, We thank Alonso and Aydin for their comments on our study of the risk of recurrent cellulitis and the role of pentraxin 3 and C-reactive protein.1 In our previous study of acute cellulitis2 we found that patients with recurrent cellulitis showed a stronger inflammatory response, as measured by peak C-reactive protein (CRP) concentration or peak leukocyte count. In the subsequent study assessing the risk of cellulitis recurrence1 we had the opportunity to test the hypothesis that high CRP or pentraxin 3 (PTX3) levels could predict further recurrence of acute cellulitis. Our results did not, however, support that hypothesis. Regarding the question of exclusion criteria, patients whose medical records were not available were excluded from the follow up study (n Z 2). One patient declined. There were no other special exclusion criteria. However, PTX3 analysis included only cases with serum sample obtained within less than three days after admission (n Z 65) as reported and discussed in our paper. Alonso and Aydin point out that several factors may affect the levels of PTX3 in humans. We agree. However, there were no statistically significant differences between recurrent and non-recurrent patients in some factors mentioned by Alonso and Aydin (Table 1). One patient had rheumatoid arthritis (recurrence) and one patient had

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Letters to the Editor

Table 1 Factors possibly affecting the levels of PTX3, as assessed in the baseline study. Frequencies and percentages are given for the clinical conditions and mean values and standard deviations for the laboratory parameters. c2 test (or Fisher’s test) or T-test are used as appropriate. Factor

Recurrence in 5 years (n Z 36)

No recurrence in 5 years (n Z 51)

p

Cardiovascular disease Renal insufficiency Immunosuppressionb Asthma ALT (U/l) Afos (U/l) Creatinine (mmol/l) Sodium (mmol/l) Potassium (mmol/l) ESRc (mm/h)

4 (11%) 1 (3%) 3 (8%) 5 (14%) 39 (28.5) 155 (61.1) 77 (18.9) 139 (3.3) 4.0 (0.46) 20 (20)

12 (24%) 3 (6%) 0 3 (6%) 44 (65.4) 151 (74.9) 80 (21.9) 140 (3.7) 4.0 (0.52) 18 (19)

0.14 0.64a 0.07a 0.27a 0.70 0.82 0.61 0.83 0.91 0.69

ALT, alanine aminotransferase, Afos, alkaline phosphatase. a Fisher’s exact test. b Immunosuppressive disease or medication. c Erythrocyte sedimentation rate as measured at the control visit (mean 34 days after admission).

dermatomyositis (no recurrence). There were no patients with ulcerative colitis or vasculitis. Thus, we believe that these conditions do not substantially skew the results of our study. Unfortunately, the medication (other than immunosuppressive drugs) or dietary food supplements used by the patients were not recorded. Additionally, some basic laboratory parameters were measured on admission to hospital. Furthermore, erythrocyte sedimentation rate (ESR) was measured in 66 cases at a scheduled follow-up visit four weeks after admission. There were no statistically significant differences in liver enzymes, creatinine, electrolytes or ESR between recurrent and non-recurrent cases (Table 1). Recurrence of cellulitis is common and prevention of it is a high priority. Antibiotic prophylaxis is effective in the prevention of recurrent cellulitis.3,4 Previous prospective5,6 and retrospective7,8 studies have assessed the risk factors for recurrence. However, a robust tool for predicting the risk of recurrence of cellulitis is still in need. We hope that our study together with the previous investigations could encourage further efforts to determine clinical factors and biomarkers which could help in optimal targeting of the antibiotic prophylaxis and other preventive measures.

Conflict of interest The authors declare that there is no conflict of interest.

Acknowledgements This study was financially supported by grants from the Academy of Finland/MICMAN Research programme 20032005, and the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, Grant number R03212.

References 1. Karppelin M, Siljander T, Aittoniemi J, Hurme M, Huttunen R, Huhtala H, et al. Predictors of recurrent cellulitis in five years. Clinical risk factors and the role of PTX3 and CRP. J Infect 2014. http://dx.doi.org/10.1016/j.jinf.2014.11.002. 2. Karppelin M, Siljander T, Vuopio-Varkila J, Kere J, Huhtala H, Vuento R, et al. Factors predisposing to acute and recurrent bacterial non-necrotizing cellulitis in hospitalized patients: a prospective case-control study. Clin Microbiol Infect 2010;16: 729e34. 3. Thomas KS, Crook AM, Nunn AJ, Foster KA, Mason JM, Chalmers JR, et al. Penicillin to prevent recurrent leg cellulitis. N Engl J Med 2013;368:1695e703. 4. Oh CC, Ko HC, Lee HY, Safdar N, Maki DG, Chlebicki MP. Antibiotic prophylaxis for preventing recurrent cellulitis: a systematic review and meta-analysis. J Infect 2014;69:26e34. €nstro €m C, Britton S. Recurrent erysipelas: predispos5. Jorup-Ro ing factors and costs of prophylaxis. Infection 1987;15:105e6. €nstro €m C, Karkkonen K, Sjo €blom AC, 6. Eriksson B, Jorup-Ro Holm SE. Erysipelas: clinical and bacteriologic spectrum and serological aspects. Clin Infect Dis 1996;23:1091e8. 7. Lewis SD, Peter GS, Gomez-Marin O, Bisno AL. Risk factors for recurrent lower extremity cellulitis in a U.S. Veterans medical center population. Am J Med Sci 2006;332:304e7. 8. McNamara DR, Tleyjeh IM, Berbari EF, Lahr BD, Martinez J, Mirzoyev SA, et al. A predictive model of recurrent lower extremity cellulitis in a population-based cohort. Arch Intern Med 2007;167:709e15.

Matti Karppelin* Department of Internal Medicine, Tampere University Hospital, P.O. Box 2000, FI-33521 Tampere, Finland €nen Jaana Syrja Department of Internal Medicine, Tampere University Hospital, P.O. Box 2000, FI-33521 Tampere, Finland

Letters to the Editor

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Medical School, University of Tampere, FI-33014 Tampereen Yliopisto, Finland *Corresponding author. Tampere University Hospital, P.O. Box 2000, 33521 Tampere, Finland. Tel.: þ358 3 3116 6639; fax: þ358 3 3116 4368.

E-mail address: [email protected] Accepted 6 January 2015 http://dx.doi.org/10.1016/j.jinf.2015.01.004 DOIs of original article: http://dx.doi.org/10.1016/j.jinf.2015.01. 002, http://dx.doi.org/10.1016/j.jinf.2014.11.002 ª 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Does pharyngeal sampling improve the detection of nasopharyngeal persistent carriers of Staphylococcus aureus?

Dear Editors, An article recently published in the Journal of Infection1 documented in depth the dynamics of acquisition and loss of carriage of Staphylococcus aureus strains in the community and identified that long-term carriage (two years) of the same strain is a relatively infrequent event (approximately 17% of the tested subjects). The authors focused their study on nasal carriage, which could have been a limitation for identifying persistent carriers. As the latter population was shown to exhibit a higher risk of S. aureus infection than intermittent or non-carriers,2,3 it is obviously important to be able to identify long-term carriers reliably. The current study was aimed to determine the additional value of pharyngeal screening for detecting persistent carriers of S. aureus, as well as the relationship between nasal and throat isolates in each individual. Ninety-three health-care workers (HCWs) were enrolled from March to April 2010 at the University Hospital of SaintEtienne, France, after they gave a written consent; they were sampled 6 or 7 times at nasal and pharyngeal sites over a 5-week period (mean of 31 days; range: 25e41 days) by a unique investigator (POV) using nylon flocked swab. After secondary exclusion of 3 subjects for, respectively, an antibiotic treatment at D4, discovery of pregnancy at D23, and missing samples, 1884 swabs were collected through 628 sampling episodes (SE) from 90 HCWs (M/F sex ratio of 0.67) exhibiting a mean age of 36.5 years (range 19.1e62.7). At inclusion, using nasal sampling only, 28.1% of HCWs were found to be S. aureus carriers whereas the proportion increased to 35.4% by combining nasal and pharyngeal sampling. The rate of nasal and pharyngeal carriage of S. aureus did not vary significantly over time according to the different SE (data not shown). S. aureus carriers were younger than non-carriers (P < 0.05 by T-test for both

sites); no association was noticed between S. aureus carriage and gender status. These data confirm that throat sampling allows detecting approximately 25% of additional S. aureus carriers4 and that the rate of S. aureus colonization decreases as people grow older.4,5 According to a previous study6 based on the carrier index (CI) (proportion of positive SE/total number of SE), HCWs were classified in persistent, intermittent and noncarriers, when the CI was 0.8,

Response to Agilli and Aydin.

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