Zoonotic Chlamydia Caviae Presenting As Community-Acquired Pneumonia

The new england journal of medicine

Correspondence

Zoonotic Chlamydia caviae Presenting as Community-Acquired Pneumonia

To the Editor: Chlamydia caviae is a member of national surveillance system for psittacosis, in the family of gram-negative intracellular bacteria which samples identified as positive in a poly- Chlamydiaceae. Bacteria of this family cause a merase-chain-reaction assay are genotyped by broad spectrum of diseases in animals and hu- sequencing a part of the gene that encodes the mans and are currently subdivided into a single outer membrane protein A, ompA5 (details are genus and 11 species.1 Among these species, provided in Sections S2 and S3 in the Supple- C. psittaci and C. abortus are known for their zoo- mentary Appendix). In one patient, chlamydia notic potential, causing psittacosis and abortion, seroconversion was detected by means of com- respectively, in humans.2,3 In contrast, only one plement fixation, which revealed an increase in case of mild conjunctivitis has previously been the antibody titer by a factor of 4 (see Section S3 documented in association with C. caviae.4 in the Supplementary Appendix for details). No We describe three unrelated cases of infec- other causes of community-acquired pneumonia tion in otherwise healthy adults in their early were found (see Section S4 in the Supplementary 30s who had respiratory failure caused by severe Appendix). Although different antibiotic regimens community-acquired pneumonia (see chest radio- were used to treat the patients, in accordance graphs in Section S1 of the Supplementary Ap- with local protocols (Table 1), all three patients pendix, available with the full text of this letter recovered after being treated with doxycycline. at NEJM.org) after exposure to ill guinea pigs One of the guinea pigs owned by Patient 2 (Table 1). The three cases, which appeared over showed signs of respiratory illness before com- a period of approximately 3 years, occurred in munity-acquired pneumonia developed in the persons from different families, at different hos- patient. C. caviae was isolated from a conjunctival pitals, and in different geographic areas. Two pa- swab. To confirm transmission between this tients were treated with mechanical ventilation guinea pig and its keeper, we performed a tandem in the intensive care unit for several days. repeat analysis and sequenced the ompA coding Chlamydia DNA was detected in specimens region in a sample of the patient’s bronchoalveo- obtained from the respiratory tract, serum, or lar lavage fluid (GenBank accession numbers, both in all three patients, and the species was KY777669 and KY777670), the guinea pig isolate identified as C. caviae by means of the Dutch (GenBank numbers, KY777661 and KY777662), and several samples from other C. caviae strains this week’s letters (GenBank numbers, KY777663–KY777668). The sequences of ompA and the single variable- 992 Zoonotic Chlamydia caviae Presenting number tandem-repeat (VNTR) region that were as Community-Acquired Pneumonia identified (from among 27 potential VNTRs) were identical in the bronchoalveolar lavage 994 Early, Goal-Directed Therapy for Septic Shock fluid from the patient and her guinea pig and — A Patient-Level Meta-Analysis different from the C. caviae reference strain GPIC 996 Buprenorphine for the Neonatal Abstinence (GenBank accession number, AE015925; details Syndrome are provided in Sections S5 through S10 in the Supplementary Appendix). This finding is in line

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C. psittaci ; C. C. caviae C. 43 34 ≤5 NA NA NA NA 171 212 <35 0–120 Female Patient 3 Fibromyalgia No treatment No September 2015 September Admission to general ward general to Admission and a dyspnoeic, indolent wild rabbit at rabbit wild indolent dyspnoeic, a and clinic) veterinary (a workplace by doxycycline by by positive PCR assay for assay PCR positive by revealed typing further vomiting, abdominal pain abdominal vomiting, Guinea pigs with conjunctivitis and rhinitis and conjunctivitis with pigs Guinea Amoxicillin plus ciprofloxacin, followed ciprofloxacin, plus Amoxicillin Radiography and sputum smear followed smear sputum and Radiography Pneumonia; hospitalization needed hospitalization Pneumonia; Fever, headache, drowsiness, nausea, drowsiness, Fever, headache, C. caviae C. 31 ≤8 NA NA NA 111 420 294 379 <38 3600 <247 33–98 Female Patient 2 4000–10,000 September 2014 September ICU admission, mechanical ventilation mechanical admission, ICU symptoms before development of patient’s of development before symptoms pneumonia community-acquired lavage fluid followed by positive PCR assay forPCR assay positive by followed fluid lavage revealed typing further psittaci ; C. cyclineciprofloxacin plus traumatic stress disorder, and obesity and disorder, stress traumatic NSAIDs, prescribed by general practitioner general by prescribed NSAIDs, hospitalization needed hospitalization Fever, coughing, shortness of breath, myalgia breath, of shortness coughing, Fever, 25 Guinea pigs at home that had respiratory had that home at pigs Guinea 25 Radiography and examination of bronchoalveolar- of examination and Radiography Penicillin plus ciprofloxacin, followed by doxy by followed ciprofloxacin, plus Penicillin Traumatic epidural hematoma (in 1991), post- 1991), (in hematoma epidural Traumatic No response to amoxicillin–clavulanic acid plusacid amoxicillin–clavulanic to response No Pneumonia and severe respiratory insufficiency;respiratory severe and Pneumonia C. caviae C. 32 ≤8 NA NA NA NA 131 485 Male 13,300 135–145 Patient 1 4000–10,000 February 2013 February Unremarkable ICU admission, mechanical ventilation mechanical admission, ICU toms before development of patient’s commu - patient’s of development before toms pneumonia nity-acquired lavage fluid followed by positive PCR assay forassay PCR positive by followed fluid lavage revealed typing further psittaci ; Chlamydia axone plus doxycycline, followed by meropen - by followed doxycycline, plus axone doxycycline plus em NSAIDs, prescribed by general practitioner general by prescribed NSAIDs, hospitalization needed hospitalization Fever, malaise, coughing, headache, myalgia headache, coughing, malaise, Fever, 2 Guinea pigs at home that had respiratory symp - respiratory had that home at pigs Guinea 2 Radiography and examination of bronchoalveolar- of examination and Radiography Ceftriaxone plus ciprofloxacin, followed by ceftri - by followed ciprofloxacin, plus Ceftriaxone No response to amoxicillin–clavulanic acid plus acid amoxicillin–clavulanic to response No Pneumonia and severe respiratory insufficiency;respiratory severe and Pneumonia ) 3 Reference range at local hospital local at range Reference Reference range at local hospital local at range Reference Reference range at local hospital local at range Reference hospital local at range Reference hospital local at range Reference Reference range at local hospital local at range Reference Reference range at local hospital local at range Reference Lactate dehydrogenase (U/liter) dehydrogenase Lactate Alkaline phosphatase (U/liter) phosphatase Alkaline (IU/liter) aminotransferase Alanine (U/liter) γ-Glutamyltransferase Sodium (mmol/liter) Sodium White-cell count (per mm (per count White-cell C-reactive protein (mg/liter) protein C-reactive Patient Data and Findings.* and Data Patient 1. Table Additional anamnesis Additional Diagnostic measures Diagnostic Treatment Characteristics Sex Medical history Medical signs Clinical Laboratory findings Laboratory During hospitalization During situation Clinical Before hospitalization Before symptoms of Appearance (yr) Age Treatment Diagnosis ICU denotes intensive care unit, NA not available, NSAIDs nonsteroidal antiinflammatory drugs, and PCR polymerase chain reactio n. *

with a C. caviae transmission event, although the Mauro De Rosa, M.D. molecular features described (see Sections S8 Dutch Food and Health Authority (NVWA) through S10 in the Supplementary Appendix) Utrecht, the Netherlands were not unique but were shared with two Ger- Hendrik I.J. Roest, D.V.M., Ph.D. man C. caviae strains. Wageningen Bioveterinary Research Altogether, the data imply that the transmission Lelystad, the Netherlands of C. caviae from guinea pig to human in these Daisy Vanrompay, Ph.D. cases resulted in severe community-acquired pneu- Ghent University monia. Both veterinarians and physicians should Ghent, Belgium be aware of the zoonotic potential of C. caviae. Edou R. Heddema, M.D., Ph.D. Although the extent to which C. caviae actually Zuyderland Medical Center contributes to community-acquired pneumonia is Sittard-Geleen, the Netherlands unclear, awareness may help to clarify this issue. Peter Schneeberger, M.D., Ph.D. Mirjam H.A. Hermans, Ph.D. Bart P. Ramakers, M.D., Ph.D. Jeroen Bosch Hospital Bernhoven Den Bosch, the Netherlands Uden, the Netherlands Drs. Ramakers and Heijne contributed equally to this letter. Marloes Heijne, D.V.M. Supported by a grant from the Dutch Ministry of Health, Wel- Wageningen Bioveterinary Research fare, and Sport through the National Institute for Public Health Lelystad, the Netherlands and the Environment, Bilthoven, the Netherlands (3910014586). [email protected] Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. Natascha Lie, M.D. Zuyderland Medical Center 1. Sachse K, Bavoil PM, Kaltenboeck B, et al. Emendation of the Heerlen, the Netherlands family Chlamydiaceae: proposal of a single genus, Chlamydia, to include all currently recognized species. Syst Appl Microbiol 2015; Thuy-Nga Le, M.D. 38:99-103. 2. Pospischil A, Thoma R, Hilbe M, Grest P, Zimmermann D, Gelderse Vallei Hospital Gebbers JO. Abortion in humans caused by Chlamydophila Ede, the Netherlands abortus (Chlamydia psittaci serovar 1). Schweiz Arch Tierheilkd Monique van Vliet, M.D. 2002;144: 463-6. (In German.) 3. Beeckman DS, Vanrompay DC. Zoonotic Chlamydophila Zuyderland Medical Center psittaci infections from a clinical perspective. Clin Microbiol Heerlen, the Netherlands Infect 2009;15:11-7. Vivian P.J. Claessen, M.D. 4. Lutz-Wohlgroth L, Becker A, Brugnera E, et al. Chlamydiales in guinea-pigs and their zoonotic potential. J Vet Med A Physiol Municipal Health Service South Limburg Pathol Clin Med 2006;53:185-93. Geleen, the Netherlands 5. Heddema ER, van Hannen EJ, Bongaerts M, et al. Typing of Chlamydia psittaci to monitor epidemiology of psittacosis and Paulien J.P. Tolsma, M.D. aid disease control in the Netherlands, 2008 to 2013. Euro Surveill Municipal Health Service Brabant Hart voor Brabant 2015;20:21026. Den Bosch, the Netherlands DOI: 10.1056/NEJMc1702983

Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis

would answer an important question — what is To the Editor: In reporting the results of their usual care? EGDT is a well-defined intervention meta-analysis of individual patient data from three to guide hemodynamic resuscitation according trials, the Protocolized Resuscitation in Sepsis to targets for central venous pressure, mean arte- Meta-Analysis (PRISM) investigators (June 8 is- rial blood pressure, urinary output, and central sue)1 conclude that early, goal-directed therapy venous oxygen saturation. (EGDT) did not result in better outcomes than usual care in the resuscitation of patients with Which monitoring tools and hemodynamic septic shock. I was hoping that the meta-analysis targets (other than central venous pressure, mean