Therapeutic monoclonal antibodies with a focus on hereditary angioedema.

Monoclonal antibodies (mAbs) have been shown to be effective and generally safe across a continually expanding list of therapeutic areas. We describe the advantages and limitations of mAbs as a therapeutic option compared with small molecules. Specifically, we discuss a novel mAb in the treatment of hereditary angioedema (HAE), a rare and potentially life-threatening condition characterized by recurrent unpredictable swelling attacks. HAE is mediated by dysregulation of plasma kallikrein activity leading to overproduction of bradykinin. Current prophylactic treatment for HAE includes androgens or replacement of the endogenous plasma kallikrein inhibitor, C1 inhibitor. However, there remains an unmet need for an effective, less burdensome treatment option. Lanadelumab is a fully human mAb targeting plasma kallikrein. Results from clinical trials, including a pivotal Phase 3 study and its ensuing open-label extension study, demonstrated that lanadelumab is associated with few treatment-related adverse events and reduced the rate of HAE attacks. This novel treatment option has the potential to significantly improve the lives of patients with HAE.

Impact of Antibiotic Stewardship Rounds in the Intensive Care Setting: A Prospective Cluster-Randomized Crossover Study.

BACKGROUND: Few groups have formally studied the effect of dedicated antibiotic stewardship rounds (ASRs) on antibiotic use (AU) in intensive care units (ICUs). METHODS: We implemented weekly ASRs using a 2-arm, cluster-randomized, crossover study in 5 ICUs at Duke University Hospital from November 2017 to June 2018. We excluded patients without an active antibiotic order, or if they had a marker of high complexity including an existing infectious disease consult, transplantation, ventricular assist device, or extracorporeal membrane oxygenation. AU during and following ICU stay for patients with ASRs was compared to the controls. We recorded the number of reviews, recommendations delivered, and responses. We evaluated change in ICU-specific AU during and after the study. RESULTS: Our analysis included 4683 patients: 2330 intervention and 2353 controls. Teams performed 761 reviews during ASRs, which excluded 1569 patients: 60% of patients off antibiotics, and 8% complex patients. Exclusions affected 88% of cardiothoracic ICU (CTICU) patients. The AU rate ratio (RR) was 0.97 (95% confidence interval [CI], .91-1.04). When CTICU was removed, the RR was 0.93 (95% CI, .89-.98). AU in the poststudy period decreased by 16% (95% CI, 11%-24%) compared to AU in the baseline period. Change in AU was differential among units: largest in the neurology ICU (-28%) and smallest in the CTICU (-2%). CONCLUSIONS: Weekly multidisciplinary ASRs was a high-resource intervention associated with a small AU reduction. The noticeable ICU AU decline over time is possibly due to indirect effects of ASRs. Effects differed among specialty ICUs, emphasizing the importance of customizing ASRs to match unit-specific population, workflow, and culture.

Impact of Oral Metronidazole, Vancomycin, and Fidaxomicin on Host Shedding and Environmental Contamination With Clostridioides difficile.

BACKGROUND: Shedding of Clostridioides difficile spores from infected individuals contaminates the hospital environment and contributes to infection transmission. We assessed whether antibiotic selection affects C. difficile shedding and contamination of the hospital environment. METHODS: In this prospective, unblinded, randomized controlled trial of hospitalized adults with C. difficile infection, patients were randomized 1:1:1 to receive fidaxomicin, oral vancomycin, or metronidazole. The primary outcome was change in environmental contamination rate during treatment. Secondary outcomes included stool shedding, total burden of contamination, and molecular relatedness of stool versus environmental C. difficile isolates. RESULTS: Of 33 patients enrolled, 31 (94%) completed the study. Fidaxomicin (-0.36 log10 colony-forming units [CFUs]/d [95% confidence interval (CI), -.52 to -.19]; P < .01) and vancomycin (-0.17 log10 CFUs/d [-.34 to -.01]; P = .05) were associated with more rapid decline in C. difficile shedding than metronidazole (-0.01 log10 CFUs/d [95% CI, -.10 to .08). Both vancomycin (6.3% [95% CI, 4.7-8.3) and fidaxomicin (13.1% [10.7-15.9]) were associated with lower rates of environmental contamination than metronidazole (21.4% [18.0-25.2]). With specific modeling of within-subject change over time, fidaxomicin (adjusted odds ratio, 0.83 [95% CI, .70-.99]; P = .04) was associated with more rapid decline in environmental contamination than vancomycin or metronidazole. Overall, 207 of 233 environmental C. difficile isolates (88.8%) matched patient stool isolates by ribotyping, without significant difference by treatment. CONCLUSIONS: Fidaxomicin, and to a lesser extent vancomycin, reduces C. difficile shedding and contamination of the hospital environment relative to metronidazole. Treatment choice may play a role in reducing healthcare-associated C. difficile transmission. CLINICAL TRIALS REGISTRATION: NCT02057198.

Tap Water Avoidance Decreases Rates of Hospital-onset Pulmonary Nontuberculous Mycobacteria.

We analyzed the impact of a hospital tap water avoidance protocol on respiratory isolation of nontuberculous mycobacteria (NTM). After protocol implementation, hospital-onset episodes of respiratory NTM isolation on high-risk units decreased from 41.0 to 9.9 episodes per 10 000 patient-days (incidence rate ratio, 0.24; 95% confidence interval, .17-.34; P < .0001).

Effects of a Collaborative, Community Hospital Network for Antimicrobial Stewardship Program Implementation.

BACKGROUND: Individual hospitals may lack expertise, data resources, and educational tools to support antimicrobial stewardship programs (ASP). METHODS: We established a collaborative, consultative network focused on hospital ASP implementation. Services included on-site expert consultation, shared database for routine feedback and benchmarking, and educational programs. We performed a retrospective, longitudinal analysis of antimicrobial use (AU) in 17 hospitals that participated for at least 36 months during 2013-2018. ASP practice was assessed using structured interviews. Segmented regression estimated change in facility-wide AU after a 1-year assessment, planning, and intervention initiation period. Year 1 AU trend (1-12 months) and AU trend following the first year (13-42 months) were compared using relative rates (RR). Monthly AU rates were measured in days of therapy (DOT) per 1000 patient days for overall AU, specific agents, and agent groups. RESULTS: Analyzed data included over 2.5 million DOT and almost 3 million patient-days. Participating hospitals increased ASP-focused activities over time. Network-wide overall AU trends were flat during the first 12 months after network entry but decreased thereafter (RR month 42 vs month 13, 0.95, 95% confidence interval [CI]: .91-.99). Large variation was seen in hospital-specific AU. Fluoroquinolone use was stable during year 1 and then dropped significantly. Other agent groups demonstrated a nonsignificant downward trajectory after year 1. CONCLUSIONS: Network hospitals increased ASP activities and demonstrated decline in AU over a 42-month period. A collaborative, consultative network is a unique model in which hospitals can access ASP implementation expertise to support long-term program growth.

Invasive Mycobacterium abscessus Complex Infection After Cardiac Surgery: Epidemiology, Management, and Clinical Outcomes.

BACKGROUND: We recently mitigated a clonal outbreak of hospital-acquired Mycobacterium abscessus complex (MABC), which included a large cluster of adult patients who developed invasive infection after exposure to heater-cooler units during cardiac surgery. Recent studies have detailed Mycobacterium chimaera infections acquired during cardiac surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive MABC infection. METHODS: We retrospectively collected clinical data on all patients who underwent cardiac surgery at our hospital and subsequently had positive cultures for MABC from 2013 through 2016. Patients with ventricular assist devices or heart transplants were excluded. We analyzed patient characteristics, antimicrobial therapy, surgical interventions, and clinical outcomes. RESULTS: Ten cardiac surgery patients developed invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting. Median time from presumed inoculation in the operating room to first positive culture was 53 days (interquartile range [IQR], 38-139 days). Disseminated infection was common, and the most frequent culture-positive sites were mediastinum (n = 7) and blood (n = 7). Patients received a median of 24 weeks (IQR, 5-33 weeks) of combination antimicrobial therapy that included multiple intravenous agents. Six patients required antibiotic changes due to adverse events attributed to amikacin, linezolid, or tigecycline. Eight patients underwent surgical management, and 6 patients required multiple sternal debridements. Eight patients died within 2 years of diagnosis, including 4 deaths directly attributable to MABC infection. CONCLUSIONS: Despite aggressive medical and surgical management, invasive MABC infection after cardiac surgery caused substantial morbidity and mortality. New treatment strategies are needed, and compliance with infection prevention guidelines remains critical.

Practical Guidance for Clinical Microbiology Laboratories: A Comprehensive Update on the Problem of Blood Culture Contamination and a Discussion of Methods for Addressing the Problem

In this review, we present a comprehensive discussion of matters related to the problem of blood culture contamination. Issues addressed include the scope and magnitude of the problem, the bacteria most often recognized as contaminants, the impact of blood culture contamination on clinical microbiology laboratory function, the economic and clinical ramifications of contamination, and, perhaps most importantly, a systematic discussion of solutions to the problem. We conclude by providing a series of unanswered questions that pertain to this important issue.

Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis.

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. METHODS: We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a 2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients), in two administrations 14 days apart. Patients assigned to lanadelumab were enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4 patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic profile of lanadelumab was assessed by measurement of plasma levels of cleaved high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and 400-mg groups as compared with the placebo group. RESULTS: No discontinuations occurred because of adverse events, serious adverse events, or deaths in patients who received lanadelumab. The most common adverse events that emerged during treatment were attacks of angioedema, injection-site pain, and headache. Dose-proportional increases in serum concentrations of lanadelumab were observed; the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma from patients with hereditary angioedema with C1 inhibitor deficiency to levels approaching that from patients without the disorder. From day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the placebo group. All patients in the 300-mg group and 82% (9 of 11) in the 400-mg group were attack-free, as compared with 27% (3 of 11) in the placebo group. CONCLUSIONS: In this small trial, administration of lanadelumab to patients with hereditary angioedema with C1 inhibitor deficiency reduced cleavage of high-molecular-weight kininogen and attacks of angioedema. (Funded by Dyax; ClinicalTrials.gov number, NCT02093923 .).

Structural basis for pH-insensitive inhibition of immunoglobulin G recycling by an anti-neonatal Fc receptor antibody.

The neonatal Fc receptor FcRn plays a critical role in the trafficking of IgGs across tissue barriers and in retaining high circulating concentrations of both IgG and albumin. Although generally beneficial from an immunological perspective in maintaining IgG populations, FcRn can contribute to the pathogenesis of autoimmune disorders when an abnormal immune response targets normal biological components. We previously described a monoclonal antibody (DX-2507) that binds to FcRn with high affinity at both neutral and acidic pH, prevents the simultaneous binding of IgG, and reduces circulating IgG levels in preclinical animal models. Here, we report a 2.5 Å resolution X-ray crystal structure of an FcRn-DX-2507 Fab complex, revealing a nearly complete overlap of the IgG-Fc binding site in FcRn by complementarity-determining regions in DX-2507. This overlap explains how DX-2507 blocks IgG binding to FcRn and thereby shortens IgG half-life by preventing IgGs from recycling back into circulation. Moreover, the complex structure explains how the DX-2507 interaction is pH-insensitive unlike normal Fc interactions and how serum albumin levels are unaffected by DX-2507 binding. These structural studies could inform antibody-based therapeutic approaches for limiting the effects of IgG-mediated autoimmune disease.

Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study.

BACKGROUND: Patients admitted to hospital can acquire multidrug-resistant organisms and Clostridium difficile from inadequately disinfected environmental surfaces. We determined the effect of three enhanced strategies for terminal room disinfection (disinfection of a room between occupying patients) on acquisition and infection due to meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, C difficile, and multidrug-resistant Acinetobacter. METHODS: We did a pragmatic, cluster-randomised, crossover trial at nine hospitals in the southeastern USA. Rooms from which a patient with infection or colonisation with a target organism was discharged were terminally disinfected with one of four strategies: reference (quaternary ammonium disinfectant except for C difficile, for which bleach was used); UV (quaternary ammonium disinfectant and disinfecting ultraviolet [UV-C] light except for C difficile, for which bleach and UV-C were used); bleach; and bleach and UV-C. The next patient admitted to the targeted room was considered exposed. Every strategy was used at each hospital in four consecutive 7-month periods. We randomly assigned the sequence of strategies for each hospital (1:1:1:1). The primary outcomes were the incidence of infection or colonisation with all target organisms among exposed patients and the incidence of C difficile infection among exposed patients in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01579370. FINDINGS: 31 226 patients were exposed; 21 395 (69%) met all inclusion criteria, including 4916 in the reference group, 5178 in the UV group, 5438 in the bleach group, and 5863 in the bleach and UV group. 115 patients had the primary outcome during 22 426 exposure days in the reference group (51·3 per 10 000 exposure days). The incidence of target organisms among exposed patients was significantly lower after adding UV to standard cleaning strategies (n=76; 33·9 cases per 10 000 exposure days; relative risk [RR] 0·70, 95% CI 0·50-0·98; p=0·036). The primary outcome was not statistically lower with bleach (n=101; 41·6 cases per 10 000 exposure days; RR 0·85, 95% CI 0·69-1·04; p=0·116), or bleach and UV (n=131; 45·6 cases per 10 000 exposure days; RR 0·91, 95% CI 0·76-1·09; p=0·303) among exposed patients. Similarly, the incidence of C difficile infection among exposed patients was not changed after adding UV to cleaning with bleach (n=38 vs 36; 30·4 cases vs 31·6 cases per 10 000 exposure days; RR 1·0, 95% CI 0·57-1·75; p=0·997). INTERPRETATION: A contaminated health-care environment is an important source for acquisition of pathogens; enhanced terminal room disinfection decreases this risk. FUNDING: US Centers for Disease Control and Prevention.

Two-Phase Hospital-Associated Outbreak of Mycobacterium abscessus: Investigation and Mitigation.

BACKGROUND: Nontuberculous mycobacteria (NTM) commonly colonize municipal water supplies and cause healthcare-associated outbreaks. We investigated a biphasic outbreak of Mycobacterium abscessus at a tertiary care hospital. METHODS: Case patients had recent hospital exposure and laboratory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015. We conducted a multidisciplinary epidemiologic, field, and laboratory investigation. RESULTS: The incidence rate of M. abscessus increased from 0.7 cases per 10000 patient-days during the baseline period (January 2013-July 2013) to 3.0 cases per 10000 patient-days during phase 1 of the outbreak (August 2013-May 2014) (incidence rate ratio, 4.6 [95% confidence interval, 2.3-8.8]; P < .001). Thirty-six of 71 (51%) phase 1 cases were lung transplant patients with positive respiratory cultures. We eliminated tap water exposure to the aerodigestive tract among high-risk patients, and the incidence rate decreased to baseline. Twelve of 24 (50%) phase 2 (December 2014-June 2015) cases occurred in cardiac surgery patients with invasive infections. Phase 2 resolved after we implemented an intensified disinfection protocol and used sterile water for heater-cooler units of cardiopulmonary bypass machines. Molecular fingerprinting of clinical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at a new hospital addition. We made several water engineering interventions to improve water flow and increase disinfectant levels. CONCLUSIONS: We investigated and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water. Healthcare facilities with endemic NTM should consider similar tap water avoidance and engineering strategies to decrease risk of NTM infection.

Inhibition of plasma kallikrein by a highly specific active site blocking antibody.

Plasma kallikrein (pKal) proteolytically cleaves high molecular weight kininogen to generate the potent vasodilator and the pro-inflammatory peptide, bradykinin. pKal activity is tightly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary angioedema (HAE) are deficient in C1-inhibitor and consequently exhibit excessive bradykinin generation that in turn causes debilitating and potentially fatal swelling attacks. To develop a potential therapeutic agent for HAE and other pKal-mediated disorders, we used phage display to discover a fully human IgG1 monoclonal antibody (DX-2930) against pKal. In vitro experiments demonstrated that DX-2930 potently inhibits active pKal (Ki = 0.120 ± 0.005 nM) but does not target either the zymogen (prekallikrein) or any other serine protease tested. These findings are supported by a 2.1-Å resolution crystal structure of pKal complexed to a DX-2930 Fab construct, which establishes that the pKal active site is fully occluded by the antibody. DX-2930 injected subcutaneously into cynomolgus monkeys exhibited a long half-life (t½ ∼ 12.5 days) and blocked high molecular weight kininogen proteolysis in activated plasma in a dose- and time-dependent manner. Furthermore, subcutaneous DX-2930 reduced carrageenan-induced paw edema in rats. A potent and long acting inhibitor of pKal activity could be an effective treatment option for pKal-mediated diseases, such as HAE.

Delay in diagnosis of invasive surgical site infections following knee arthroplasty versus hip arthroplasty.

BACKGROUND: The timing of diagnosis of invasive surgical site infection (SSI) following joint replacement surgery is an important criterion used to determine subsequent medical and surgical management. METHODS: We compared time to diagnosis of invasive SSI following hip vs knee arthroplasty. SSIs were included in the analysis if they occurred within 365 days following procedures performed from 1 January 2007 through 31 December 2011 at 36 community acute care hospitals and 1 ambulatory surgery center in the Duke Infection Control Outreach Network. A Cox regression model was fitted to estimate the association between procedure type and time to diagnosis of SSI, adjusted for age, pathogen virulence, American Society of Anesthesiologists' score, and hospital surgical volume. RESULTS: Six hundred sixty-one invasive SSIs were identified; 401 (61%) occurred following knee arthroplasties. The median time to diagnosis of SSI was 25 days (interquartile range [IQR], 17-48 days) following hip arthroplasty vs 42 days (IQR, 21-114 days) following knee arthroplasty (unadjusted hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.37-1.87; P < .001). Time to diagnosis of invasive SSI remained significantly shorter for hip than for knee arthroplasties after adjusting for age, pathogen virulence, and hospital surgical volume (HR, 1.51; 95% CI, 1.28-1.78; P < .001). CONCLUSIONS: The diagnosis of invasive SSI was delayed following knee arthroplasty compared with hip arthroplasty. We hypothesize that differences in symptom manifestation and disparities in access to care may contribute to the observed differential timing of diagnosis. Our findings have important implications for the management of prosthetic joint infections, because treatment strategies depend on the timing of diagnosis.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Challenges in Preparation of Cumulative Antibiogram Reports for Community Hospitals.

Knowledge of local antimicrobial resistance is critical for management of infectious diseases. Community hospitals' compliance with Clinical and Laboratory Standards Institute (CLSI) guidance for creation of cumulative antibiograms is uncertain. This descriptive cohort study of antibiogram reporting practices included community hospitals enrolled in the Duke Infection Control Outreach Network. Cumulative antibiograms from 2012 were reviewed for criteria on reporting practices and compliance with CLSI guidelines. Microbiology personnel were sent a voluntary, electronic survey on antibiogram preparation practices. Data were compiled using descriptive statistics. Thirty-two of 37 (86%) hospitals provided antibiograms; 26 of 37 (70%) also provided survey responses. Twelve (38%) antibiograms specified methods used for compiling data and exclusion of duplicates. Eight (25%) reported only species with >30 isolates. Of the 24 that did not follow the 30-isolate rule, 3 (13%) included footnotes to indicate impaired statistical validity. Twenty (63%) reported at least 1 pathogen-drug combination not recommended for primary or supplemental testing per CLSI. Thirteen (41%) separately reported methicillin-resistant and -susceptible Staphylococcus aureus. Complete compliance with CLSI guidelines was observed in only 3 (9%) antibiograms. Survey respondents' self-assessment of full or partial compliance with CLSI guidelines was 50% and 15%, respectively; 33% reported uncertainty with CLSI guidelines. Full adherence to CLSI guidelines for hospital antibiograms was uncommon. Uncertainty about CLSI guidelines was common. Alternate strategies, such as regional antibiograms using pooled data and educational outreach efforts, are needed to provide reliable and appropriate susceptibility estimates for community hospitals.

Widespread dissemination of CTX-M-15 genotype extended-spectrum-ß-lactamase-producing enterobacteriaceae among patients presenting to community hospitals in the southeastern United States.

Extended-spectrum-ß-lactamase (ESBL)-producing organisms are increasingly prevalent. We determined the characteristics of 66 consecutive ESBL-producing isolates from six community hospitals in North Carolina and Virginia from 2010 to 2012. Fifty-three (80%) ESBL-producing isolates contained CTX-M enzymes; CTX-M-15 was found in 68% of Escherichia coli and 73% of Klebsiella isolates. Sequence type 131 (ST131) was the commonest type of E. coli, accounting for 48% of CTX-M-15-producing and 66% of CTX-M-14-producing isolates. In conclusion, the CTX-M genotype and ST131 E. coli were common among ESBL isolates from U.S. community hospitals.

Necrotizing fasciitis caused by Haemophilus influenzae serotype f.

Haemophilus influenzae is a rare cause of soft tissue infection. In this report, we present a case of multifocal necrotizing fasciitis in a healthy adult patient, secondary to Haemophilus influenzae serotype f infection, and we review literature on this rare cause of necrotizing fasciitis.

Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group.

Q fever, a zoonotic disease caused by the bacterium Coxiella burnetii, can cause acute or chronic illness in humans. Transmission occurs primarily through inhalation of aerosols from contaminated soil or animal waste. No licensed vaccine is available in the United States. Because many human infections result in nonspecific or benign constitutional symptoms, establishing a diagnosis of Q fever often is challenging for clinicians. This report provides the first national recommendations issued by CDC for Q fever recognition, clinical and laboratory diagnosis, treatment, management, and reporting for health-care personnel and public health professionals. The guidelines address treatment of acute and chronic phases of Q fever illness in children, adults, and pregnant women, as well as management of occupational exposures. These recommendations will be reviewed approximately every 5 years and updated to include new published evidence.