Claessen, Vivian P.J.

Heddema, Edou R.

Heijne, Marloes

Hermans, Mirjam H.A.

Le, Thuy Nga

Lie, Natascha

Ramakers, Bart P.

Roest, Hendrik I.J.

Rosa, De, Mauro

Schneeberger, Peter

Tolsma, Paulien J.P.

Vanrompay, Daisy

Vliet, Van, Monique

Ramakers, Bart P

Thuy-Nga Le, Thuy-Nga Le

van Vliet, Monique

Claessen, Vivian PJ

Tolsma, Paulien JP

De Rosa, Mauro

Roest, Hendrik IJ

Heddema, Edou R

Hermans, Mirjam HA

Ghent University Academic Bibliography

Corr e spondenceT h e  n e w  e ngl a nd  j o u r na l  o f  m e dic i n en engl j med 377;10 nejm.org September 7, 2017Zoonotic Chlamydia caviae Presenting as Community-Acquired PneumoniaTo the Editor: Chlamydia caviae is a member of the family of gram-negative intracellular bacteria Chlamydiaceae. Bacteria of this family cause a broad spectrum of diseases in animals and hu-mans and are currently subdivided into a single genus and 11 species.1 Among these species, C. psittaci and C. abortus are known for their zoo-notic potential, causing psittacosis and abortion, respectively, in humans.2,3 In contrast, only one case of mild conjunctivitis has previously been documented in association with C. caviae.4We describe three unrelated cases of infec-tion in otherwise healthy adults in their early 30s who had respiratory failure caused by severe community-acquired pneumonia (see chest radio-graphs in Section S1 of the Supplementary Ap-pendix, available with the full text of this letter at NEJM.org) after exposure to ill guinea pigs (Table 1). The three cases, which appeared over a period of approximately 3 years, occurred in persons from different families, at different hos-pitals, and in different geographic areas. Two pa-tients were treated with mechanical ventilation in the intensive care unit for several days.Chlamydia DNA was detected in specimens obtained from the respiratory tract, serum, or both in all three patients, and the species was identified as C. caviae by means of the Dutch national surveillance system for psittacosis, in which samples identified as positive in a poly-merase-chain-reaction assay are genotyped by sequencing a part of the gene that encodes the outer membrane protein A, ompA5 (details are provided in Sections S2 and S3 in the Supple-mentary Appendix). In one patient, chlamydia seroconversion was detected by means of com-plement fixation, which revealed an increase in the antibody titer by a factor of 4 (see Section S3 in the Supplementary Appendix for details). No other causes of community-acquired pneumonia were found (see Section S4 in the Supplementary Appendix). Although different antibiotic regimens were used to treat the patients, in accordance with local protocols (Table 1), all three patients recovered after being treated with doxycycline.One of the guinea pigs owned by Patient 2 showed signs of respiratory illness before com-munity-acquired pneumonia developed in the patient. C. caviae was isolated from a conjunctival swab. To confirm transmission between this guinea pig and its keeper, we performed a tandem repeat analysis and sequenced the ompA coding region in a sample of the patient’s bronchoalveo-lar lavage fluid (GenBank accession numbers, KY777669 and KY777670), the guinea pig isolate (GenBank numbers, KY777661 and KY777662), and several samples from other C. caviae strains (GenBank numbers, KY777663–KY777668). The sequences of ompA and the single variable-number tandem-repeat (VNTR) region that were identified (from among 27 potential VNTRs) were identical in the bronchoalveolar lavage fluid from the patient and her guinea pig and different from the C. caviae reference strain GPIC (GenBank accession number, AE015925; details are provided in Sections S5 through S10 in the Supplementary Appendix). This finding is in line this week’s letters992 Zoonotic Chlamydia caviae Presenting  as Community-Acquired Pneumonia994 Early, Goal-Directed Therapy for Septic Shock  — A Patient-Level Meta-Analysis996 Buprenorphine for the Neonatal Abstinence SyndromeThe New England Journal of Medicine Downloaded from nejm.org on September 11, 2017. For personal use only. No other uses without permission.  Copyright © 2017 Massachusetts Medical Society. All rights reserved. Correspondencen engl j med 377;10 nejm.org September 7, 2017Table 1. Patient Data and Findings.*CharacteristicsPatient 1Patient 2Patient 3Before hospitalizationAppearance of symptomsFebruary 2013September 2014September 2015Age (yr)323134SexMaleFemaleFemaleMedical historyUnremarkableTraumatic epidural hematoma (in 1991), post-traumatic stress disorder, and obesityFibromyalgiaClinical signsFever, malaise, coughing, headache, myalgiaFever, coughing, shortness of breath, myalgiaFever, headache, drowsiness, nausea, vomiting, abdominal painTreatmentNo response to amoxicillin–clavulanic acid plus NSAIDs, prescribed by general practitionerNo response to amoxicillin–clavulanic acid plus NSAIDs, prescribed by general practitionerNo treatmentDiagnosisPneumonia and severe respiratory insufficiency; hospitalization neededPneumonia and severe respiratory insufficiency; hospitalization neededPneumonia; hospitalization neededDuring hospitalizationClinical situationICU admission, mechanical ventilationICU admission, mechanical ventilationAdmission to general wardLaboratory findingsC-reactive protein (mg/liter)485379212Reference range at local hospital≤8≤8≤5White-cell count (per mm3 )13,3003600NAReference range at local hospital4000–10,0004000–10,000Sodium (mmol/liter)131NANAReference range at local hospital135–145NAAlkaline phosphatase (U/liter)NA294171Reference range at local hospital33–980–120Alanine aminotransferase (IU/liter)NANA43Reference range at local hospital<35γ-Glutamyltransferase (U/liter)NA111NAReference range at local hospital<38Lactate dehydrogenase (U/liter)NA420NAReference range at local hospital<247Diagnostic measuresRadiography and examination of bronchoalveolar-lavage fluid followed by positive PCR assay for Chlamydia psittaci; further typing revealed C. caviaeRadiography and examination of bronchoalveolar-lavage fluid followed by positive PCR assay for C. psittaci; further typing revealed C. caviaeRadiography and sputum smear followed by positive PCR assay for C. psittaci; further typing revealed C. caviaeTreatmentCeftriaxone plus ciprofloxacin, followed by ceftri-axone plus doxycycline, followed by meropen-em plus doxycyclinePenicillin plus ciprofloxacin, followed by doxy-cycline plus ciprofloxacinAmoxicillin plus ciprofloxacin, followed  by doxycyclineAdditional anamnesis2 Guinea pigs at home that had respiratory symp-toms before development of patient’s commu-nity-acquired pneumonia25 Guinea pigs at home that had respiratory symptoms before development of patient’s community-acquired pneumoniaGuinea pigs with conjunctivitis and rhinitis and a dyspnoeic, indolent wild rabbit at workplace (a veterinary clinic)*  ICU denotes intensive care unit, NA not available, NSAIDs nonsteroidal antiinflammatory drugs, and PCR polymerase chain reaction.The New England Journal of Medicine Downloaded from nejm.org on September 11, 2017. For personal use only. No other uses without permission.  Copyright © 2017 Massachusetts Medical Society. All rights reserved. T h e  n e w  e ngl a nd  j o u r na l  o f  m e dic i n en engl j med 377;10 nejm.org September 7, 2017with a C. caviae transmission event, although the molecular features described (see Sections S8 through S10 in the Supplementary Appendix) were not unique but were shared with two Ger-man C. caviae strains.Altogether, the data imply that the transmission of C. caviae from guinea pig to human in these cases resulted in severe community-acquired pneu-monia. Both veterinarians and physicians should be aware of the zoonotic potential of C. caviae. Although the extent to which C. caviae actually contributes to community-acquired pneumonia is unclear, awareness may help to clarify this issue.Bart P. Ramakers, M.D., Ph.D.Bernhoven Uden, the NetherlandsMarloes Heijne, D.V.M.Wageningen Bioveterinary Research Lelystad, the Netherlands marloes.heijne@wur.nlNatascha Lie, M.D.Zuyderland Medical Center Heerlen, the NetherlandsThuy-Nga Le, M.D.Gelderse Vallei Hospital Ede, the NetherlandsMonique van Vliet, M.D.Zuyderland Medical Center Heerlen, the NetherlandsVivian P.J. Claessen, M.D.Municipal Health Service South Limburg Geleen, the NetherlandsPaulien J.P. Tolsma, M.D.Municipal Health Service Brabant Hart voor Brabant Den Bosch, the NetherlandsMauro De Rosa, M.D.Dutch Food and Health Authority (NVWA) Utrecht, the NetherlandsHendrik I.J. Roest, D.V.M., Ph.D.Wageningen Bioveterinary Research Lelystad, the NetherlandsDaisy Vanrompay, Ph.D.Ghent University Ghent, BelgiumEdou R. Heddema, M.D., Ph.D.Zuyderland Medical Center Sittard-Geleen, the NetherlandsPeter Schneeberger, M.D., Ph.D. Mirjam H.A. Hermans, Ph.D.Jeroen Bosch Hospital Den Bosch, the NetherlandsDrs. Ramakers and Heijne contributed equally to this letter.Supported by a grant from the Dutch Ministry of Health, Wel-fare, and Sport through the National Institute for Public Health and the Environment, Bilthoven, the Netherlands (3910014586).Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.1. Sachse K, Bavoil PM, Kaltenboeck B, et al. Emendation of the family Chlamydiaceae: proposal of a single genus, Chlamydia, to include all currently recognized species. Syst Appl Microbiol 2015; 38: 99-103.2. Pospischil A, Thoma R, Hilbe M, Grest P, Zimmermann D, Gebbers JO. Abortion in humans caused by Chlamydophila abortus (Chlamydia psittaci serovar 1). Schweiz Arch Tierheilkd 2002; 144: 463-6. (In German.)3. Beeckman DS, Vanrompay DC. Zoonotic Chlamydophila psittaci infections from a clinical perspective. Clin Microbiol Infect 2009; 15: 11-7.4. Lutz-Wohlgroth L, Becker A, Brugnera E, et al. Chlamydiales in guinea-pigs and their zoonotic potential. J Vet Med A Physiol Pathol Clin Med 2006; 53: 185-93.5. Heddema ER, van Hannen EJ, Bongaerts M, et al. Typing of Chlamydia psittaci to monitor epidemiology of psittacosis and aid disease control in the Netherlands, 2008 to 2013. Euro Surveill 2015; 20: 21026.DOI: 10.1056/NEJMc1702983Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-AnalysisTo the Editor: In reporting the results of their meta-analysis of individual patient data from three trials, the Protocolized Resuscitation in Sepsis Meta-Analysis (PRISM) investigators (June 8 is-sue)1 conclude that early, goal-directed therapy (EGDT) did not result in better outcomes than usual care in the resuscitation of patients with septic shock. I was hoping that the meta-analysis would answer an important question — what is usual care? EGDT is a well-defined intervention to guide hemodynamic resuscitation according to targets for central venous pressure, mean arte-rial blood pressure, urinary output, and central venous oxygen saturation.Which monitoring tools and hemodynamic targets (other than central venous pressure, mean The New England Journal of Medicine Downloaded from nejm.org on September 11, 2017. For personal use only. No other uses without permission.  Copyright © 2017 Massachusetts Medical Society. All rights reserved. 

Zoonotic chlamydia caviae presenting as community-acquired pneumonia

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