Gram-Negative, Fastidious, and Vector-Borne Agents of Bloodstream Infection

Gram-negative organisms reach the blood-culture bench along three different routes, and each route changes the laboratory work. Most gram-negative pathogens, including the fastidious HACEK group and Brucella, grow in a continuous-monitoring blood culture within the standard incubation period of about 5 days, so the work is identification and correct susceptibility reporting.¹ A second, smaller group concentrates in the reticuloendothelial system, and bone marrow culture can recover these organisms when peripheral blood cultures have failed. A third group of vector-borne and zoonotic bacteria circulates in blood but grows poorly or never in routine bottles, so the diagnostic specimen is blood, buffy coat, or serum tested by serology, stained smear, or nucleic acid amplification.

Blood-culture collection, bottle monitoring, and the positive-bottle workup are covered in Blood Cultures and Gram-Positive Blood Isolates. General transport, direct stains, media, incubation, and staged reporting are covered in Specimen Collection, Transport, and Primary Processing in Microbiology. This module begins where a bottle has flagged positive with gram-negative cocci or bacilli on the Gram stain, or where the clinical picture points to an organism a routine bottle will rarely deliver.

Gram-negative cocci: Neisseria

Characteristics. Neisseria species are nonmotile, catalase- and oxidase-positive gram-negative cocci, typically paired with flattened adjacent sides that give a kidney-bean or coffee-bean appearance; young cultures may also show tetrads. Many strains require blood, serum, cholesterol, or oleic acid supplementation to counteract inhibitory fatty acids in the medium, and N. gonorrhoeae and N. meningitidis generally require added CO₂ for primary isolation, a requirement that varies by strain and often fades on subculture.²

Clinical significance. N. meningitidis colonizes the upper respiratory mucosa. Most carriers develop group-specific bactericidal antibody within 7 to 10 days and remain well, while a minority progress to meningococcemia and meningitis, sometimes with pleuritis, pericarditis, or arthritis. The organism’s lipopolysaccharide endotoxin activates the clotting cascade, and the resulting microvascular fibrin deposition, hemorrhage, and shock produce the petechial-to-ecchymotic rash of meningococcemia. A blood or cerebrospinal-fluid recovery of N. meningitidis is a critical result that follows the laboratory’s urgent-notification procedure.²

N. gonorrhoeae is considered pathogenic in every specimen, with or without symptoms. Urethral infection in men usually announces itself; endocervical infection in women is commonly asymptomatic until ascending infection has produced pelvic inflammatory disease, with tubal scarring that predisposes to infertility or ectopic pregnancy.² Antigenically variable type IV pili mediate adherence and are a principal gonococcal virulence factor.² Genital-tract collection and the combined gonorrhea and chlamydia molecular workflow are taught with genital-tract bacteriology; what matters here is how the organism behaves as an isolate.

Specimen handling and media. Pathogenic Neisseria are damaged by drying, temperature extremes, and delay, so material is inoculated directly to warmed media whenever possible and incubated promptly at 35 °C to 36.5 °C in about 5% CO₂, supplied by a CO₂ incubator, a candle-extinction jar, or a CO₂-generating tablet system. Media sent to a reference laboratory are incubated overnight first so growth is established before transport.³ Selective chocolate-based media for N. gonorrhoeae combine an inhibitor of gram-positive organisms (vancomycin in modified Thayer-Martin and Martin-Lewis media, lincomycin in some New York City-type formulations), colistin against other gram-negative organisms, an antifungal agent (nystatin, anisomycin, or amphotericin B), and trimethoprim to suppress swarming Proteus. Some gonococcal strains are inhibited by the vancomycin in selective media, so a nonselective chocolate agar plate is inoculated in parallel when the specimen comes from a sterile site or recovery is critical.³

Identification. A typical colony on selective medium with a positive oxidase reaction and gram-negative diplococci on smear supports a presumptive identification of N. gonorrhoeae, which is sufficient for the clinician to begin therapy. Confirmatory testing by a method with a different principle is still required before the isolate is reported as N. gonorrhoeae, because other Neisseria species grow on the same media. In suspected sexual assault or abuse, the isolate must be confirmed by two tests of different principles and preserved for possible retesting.³

Classic confirmation uses acid production from carbohydrates in cystine trypticase agar (CTA) base medium (glucose, maltose, lactose, sucrose, and fructose, with a carbohydrate-free control), read at 24-hour intervals for up to 72 hours; commercial enzyme-substrate and rapid carbohydrate-utilization kits give the same answers in 1 to 4 hours.²

Casually read color changes are the classic error: a misread can report N. meningitidis, N. cinerea, or Kingella denitrificans as N. gonorrhoeae.³ An occasional N. meningitidis isolate gives aberrant glucose-negative, maltose-negative, or fully asaccharolytic results; when meningococcus is still suspected, slide agglutination with grouping antisera resolves the identification. Moraxella catarrhalis is separated from the asaccharolytic neisseriae by its positive DNase and butyrate esterase reactions.²

For urogenital specimens, nucleic acid amplification testing (NAAT) has largely replaced culture because it is more sensitive and works on nonviable organisms, an important advantage for so fragile an organism.^3,4

Resistance notes. Circulating US gonococci are inadequately susceptible to penicillin and tetracycline, so those drugs are never assumed active. Symptoms that persist after treatment call for culture and antimicrobial susceptibility testing, and pharyngeal gonorrhea requires a test of cure 7 to 14 days after treatment, by culture or NAAT, with susceptibility testing of any positive test-of-cure culture. A chromogenic cephalosporin (nitrocefin) test detects β-lactamase production and still serves surveillance and isolate characterization, although it no longer guides therapy. Susceptibility methods and interpretive criteria are taught with antimicrobial susceptibility testing.⁴

Gram-negative nonfermenting bacilli

Nonfermenters are gram-negative bacilli that fail to ferment glucose or other carbohydrates, using oxidative pathways or none at all. They account for roughly 15% of gram-negative bacilli recovered in clinical laboratories and live in soil, water, and moist hospital environments, appearing on patients mainly as health-care-associated colonizers. Pseudomonas aeruginosa is the most frequently recovered clinically significant nonfermenter; most of the remainder are Acinetobacter species, Stenotrophomonas maltophilia, and the Burkholderia cepacia complex.²

Pseudomonas aeruginosa. An aerobic, catalase- and oxidase-positive gram-negative bacillus with oxidative metabolism, motile by polar flagella. It thrives in nearly any moist reservoir, including medical equipment, disinfectant solutions, and soaps, and colonization increases with length of hospitalization. Serious infection follows burns, surgical wounds, urinary instrumentation, hematologic and immunologic disease, cystic fibrosis, and mechanical ventilation. Its virulence factors include a slime polysaccharide, endotoxin, complement-inactivating proteases, and exotoxin A, which ADP-ribosylates elongation factor 2, shutting down host protein synthesis and producing local tissue necrosis.²

Presumptive recognition rests on a grape-like or corn-tortilla odor, rough or ground-glass colonies on blood agar, and pigment: blue-green pyocyanin, yellow-green fluorescent pyoverdin, or both, often with a metallic colony sheen. A positive oxidase reaction, growth at 42 °C, and an alkaline slant with no change in the butt on triple sugar iron agar complete the presumptive identification.² Clinically significant isolates receive susceptibility testing. P. aeruginosa is intrinsically resistant to amoxicillin-clavulanate, ceftriaxone, trimethoprim-sulfamethoxazole, the tetracyclines, ertapenem, and tigecycline, so an apparently susceptible result for one of these agents is suppressed under the intrinsic-resistance rules of the laboratory’s adopted CLSI M100 edition.⁵

Acinetobacter. Short rod-shaped to coccoid, nonmotile, oxidase-negative, strictly aerobic organisms that decolorize poorly on Gram stain and can be mistaken for gram-positive cocci. They inhabit soil and water and occasionally healthy skin, and they cause health-care-associated bacteremia, pneumonia, bacteriuria, and wound infection. A negative oxidase reaction, nonmotility, and failure to reduce nitrate separate the genus from Pseudomonas; purplish colonies on MacConkey agar from crystal violet uptake, without lactose fermentation, are characteristic.² Carbapenem-resistant A. baumannii (CRAB) is a major treatment problem; current IDSA guidance builds therapy on sulbactam-durlobactam combined with a carbapenem, so accurate species-level identification and carbapenem results carry direct clinical weight.⁶

Burkholderia cepacia complex. Aerobic, non-spore-forming, catalase-positive gram-negative rods, motile by a polar flagellum except for nonmotile B. mallei. The complex, at least 20 closely related species, is an important health-care-associated pathogen in cystic fibrosis and chronic granulomatous disease, where chronic infection accelerates decline. Complex members are phenotypically nearly indistinguishable from one another and from B. gladioli, Ralstonia, Cupriavidus, and Pandoraea, so species-level confirmation is molecular or by validated mass spectrometry.² The complex is intrinsically resistant to the aminoglycosides and the polymyxins. Meropenem, trimethoprim-sulfamethoxazole, ceftazidime, minocycline, and levofloxacin have CLSI breakpoints for the complex and must always be tested, because repeated treatment courses in chronically infected patients select acquired resistance.⁵

Stenotrophomonas maltophilia. An opportunistic health-care-associated pathogen favored by mechanical ventilation, broad-spectrum antibiotic exposure, catheters, and neutropenia, and a respiratory colonizer in cystic fibrosis, so distinguishing infection from colonization precedes any treatment decision. Distinguishing bench features are a negative oxidase reaction paired with positive DNase activity, lavender-green colonies with an ammonia-like odor on blood and MacConkey agar, motility, and oxidative utilization of glucose and maltose.² The organism is intrinsically resistant to the carbapenems, a clinically important trap: carbapenem therapy aimed at a presumed Pseudomonas or Acinetobacter infection leaves S. maltophilia untreated. Current IDSA guidance prefers cefiderocol for invasive infection and expects ceftazidime to be inactive regardless of an in vitro result, so the laboratory’s reporting rules for this organism matter as much as its identification.^5,6

Less commonly encountered nonfermenters, among them Alcaligenes, Achromobacter, Chryseobacterium, Brevundimonas, Comamonas, and Ralstonia, are usually colonizers or contaminants. Repeated recovery from a sterile site, or recovery from an immunosuppressed patient with an indwelling device, marks such an isolate as clinically significant.²

HACEK organisms and Haemophilus identification

The HACEK acronym groups fastidious, slow-growing gram-negative organisms that share oral and upper-respiratory carriage and a predilection for subacute bacterial endocarditis: Haemophilus species (particularly H. parainfluenzae), Aggregatibacter species (including A. aphrophilus and A. actinomycetemcomitans, both formerly classified with Haemophilus), Cardiobacterium hominis, Eikenella corrodens, and Kingella species. Historically these organisms were considered hard to recover, and laboratories extended incubation for suspected HACEK endocarditis. With current continuous-monitoring systems that practice is obsolete: HACEK organisms are reliably detected within the standard 5-day incubation, and extended incubation with terminal blind subculture adds nothing. Species-level identification, usually by mass spectrometry, may still take several days after the bottle signals.¹

Haemophilus growth factors. Haemophilus species are oxidase-positive, facultatively anaerobic, small pleomorphic gram-negative rods or coccobacilli defined at the bench by their requirements for X factor (hemin) and V factor (NAD). Chocolate agar supplies both factors from heat-lysed blood; on media lacking free NAD, a streak of Staphylococcus aureus releases it, and dependent colonies satellite around the streak. The porphyrin test identifies X-factor-independent species directly: they convert δ-aminolevulinic acid to porphobilinogen and porphyrins, detected as a red color with Kovac’s reagent or red fluorescence under a Wood’s lamp, while X-dependent species cannot.²

Haemophilus influenzae. The polysaccharide capsule, in six serotypes designated a through f, drives invasive disease; conjugate vaccination sharply reduced invasive type b disease, and acapsular nontypeable strains are now the most frequent cause of invasive H. influenzae infection in the United States as well as the dominant cause of otitis media and exacerbations of chronic bronchitis.⁷ H. parainfluenzae is usually a pharyngeal commensal but occasionally produces similar illness and endocarditis.²

CLSI recommends testing blood and cerebrospinal-fluid isolates of H. influenzae against ampicillin, a third-generation cephalosporin, chloramphenicol, and meropenem.⁵ About 28% of invasive US isolates are ampicillin-resistant, nearly always through a TEM-1 or ROB-1 β-lactamase detectable with a nitrocefin screen.⁸ The screen has a defined blind spot: β-lactamase-negative, ampicillin-resistant (BLNAR) strains carry altered penicillin-binding proteins, so a negative β-lactamase screen by itself cannot establish susceptibility to ampicillin, amoxicillin-clavulanate, or cefuroxime, and laboratories weigh local BLNAR rates when deciding whether full susceptibility testing must accompany the screen. β-Lactamase-producing strains remain susceptible to ceftriaxone and cefotaxime, and ceftriaxone and levofloxacin susceptibility has remained nearly universal in recent US series.⁹

Other HACEK members. Aggregatibacter aphrophilus overlaps phenotypically with H. parainfluenzae and the other HACEK species, so mass spectrometry or molecular methods make the species call. Eikenella corrodens, an oral commensal, appears in endocarditis and also in abscesses, cellulitis, and human-bite wound infections, usually as part of a mixed flora. Cardiobacterium hominis and Kingella species share the same oral carriage and endocarditis association.²

H. ducreyi, included here for its genus, causes chancroid, a genital ulcer disease. Its Gram stain shows gram-negative bacilli in parallel rows and clusters, the school-of-fish arrangement, and culture requires heavily enriched vancomycin-containing media incubated at about 33 °C in a humid, CO₂-enriched atmosphere. The chancroid workup is taught with genital-tract bacteriology.²

Bone marrow culture

Bone marrow culture is requested when an intracellular or reticuloendothelial-system pathogen is suspected and peripheral blood cultures have been unrevealing, classically for Brucella species and Salmonella enterica serotype Typhi. Both organisms concentrate in reticuloendothelial tissue, including marrow, so marrow culture keeps its yield in chronic or relapsing disease and after antimicrobial exposure has suppressed peripheral bacteremia; in typhoid fever, marrow culture remains positive more often than blood culture once therapy has begun.¹⁰ On continuous-monitoring systems Brucella is typically detected within the standard incubation period, most positives flagging by about day 7, so routine extended incubation is no longer required.¹ Suspected brucellosis must be communicated to the laboratory in advance: the organism is a frequent cause of laboratory-acquired infection, and suspicion triggers the biosafety-cabinet and public-health referral procedure. Identification and containment of Brucella and Salmonella Typhi are taught with enteric and select-agent bacteriology.

Vector-borne and zoonotic agents diagnosed from blood or serum

A group of spirochetal, rickettsial, and related intracellular bacteria produce systemic bloodstream illness after an arthropod bite or animal contact, and routine blood-culture bottles recover them poorly or never. For these agents the laboratory contribution is choosing the right specimen and test (serology, stained blood smear, or nucleic acid amplification) and reading the result against the timing of the illness. Serologic method mechanics are taught with immunology; this section covers organism-level test selection and interpretation.

Lyme borreliosis

Borrelia burgdorferi sensu stricto and, rarely, B. mayonii cause Lyme disease in the United States, the latter in the upper Midwest; B. garinii and B. afzelii are Eurasian genospecies. Ixodes hard ticks transmit the spirochete, and in most cases the tick must be attached for more than 24 hours before transmission occurs.¹¹

Diagnosis rests on serology, because spirochete numbers in blood and cerebrospinal fluid are too low for culture or amplification to work reliably. CDC’s two-tiered algorithm begins with a sensitive first-tier enzyme immunoassay; a positive or equivocal result reflexes to a second tier, either an IgM and IgG immunoblot or, in modified two-tiered testing cleared by FDA in 2019, a second, different enzyme immunoassay.^12,13 Band-count criteria apply only to immunoblots: an IgG blot is positive with 5 of 10 defined bands, an IgM blot with 2 of 3.¹⁴ A positive IgM result is disregarded when the illness has lasted more than 30 days, because by then a true infection has produced IgG. Serology may be falsely negative during the first 4 to 6 weeks of infection, so erythema migrans after a plausible exposure is treated as a clinical diagnosis without waiting for antibody, and titers stay elevated long after cure, so serology never measures treatment response.¹² An antibody index comparing cerebrospinal fluid with serum supports neuroborreliosis, and nucleic acid amplification performs best on synovial fluid in Lyme arthritis, where organism burden is highest.¹²

Southern tick-associated rash illness (STARI) follows a lone star tick bite with an erythema migrans-like rash; its cause is unknown, Lyme serology is negative, and no diagnostic laboratory test exists.¹⁵

Relapsing fever

Louse-borne relapsing fever (B. recurrentis, transmitted by the human body louse from a purely human reservoir) and soft tick relapsing fever (several Borrelia species transmitted by Ornithodoros soft ticks) produce cycles of recurring fever as the spirochete varies its surface antigens, escapes the antibody response, and re-emerges. Spirochetemia peaks during fever, so peripheral blood collected during a febrile episode is the classic specimen: spirochetes are found by darkfield examination or on a stained smear, with Wright-Giemsa, acridine orange, or fluorescent antibody staining. Polymerase chain reaction (PCR) on whole blood is more sensitive than microscopy and can stay positive between febrile episodes and early in treatment, although many assays cannot separate the relapsing-fever species from one another. Serology is most informative 14 days or more after onset, and antigenic variability plus cross-reactivity with the Lyme borreliae limit it; assays using the GlpQ antigen, which the Lyme group lacks, are more specific for relapsing fever.¹⁶

Leptospirosis

Leptospira species are tightly coiled spirochetes with hooked ends that give a question-mark shape. Rodents are the principal reservoir, shedding organisms in urine, and infection follows contact with contaminated water or soil. Illness is classically biphasic, a bacteremic phase followed by an immune phase as antibody appears. During the first week of illness, real-time PCR on whole blood provides the early confirmed diagnosis; after the first week, urine becomes the better PCR specimen. The microscopic agglutination test (MAT), performed with live antigen in reference laboratories, is the serologic reference method: agglutinating antibody appears toward the end of the first week, peaks at 3 to 4 weeks, and can persist for years. Culture is insensitive and slow, and is never the sole method: Fletcher or Ellinghausen-McCullough-Johnson-Harris (EMJH) medium is incubated at 28 °C to 30 °C in the dark and examined weekly by darkfield microscopy, for up to about 13 weeks, for spinning hooked organisms growing below the surface.¹⁷

Rickettsioses and scrub typhus

Rickettsia species are small, obligately intracellular gram-negative bacilli that escape the phagosome with their own phospholipase and replicate free in the cytosol; spotted-fever-group organisms additionally hijack host actin to propel themselves from cell to cell, spreading through vascular endothelium and producing vasculitis, while typhus-group organisms accumulate inside the cell until it ruptures. Orientia tsutsugamushi, the agent of scrub typhus, is a related but distinct genus.²

Treatment across the group is empiric, because laboratory confirmation is retrospective. The indirect immunofluorescence assay (IFA) is the serologic reference standard and is insensitive during the first week of illness, when most patients present; confirmation requires a fourfold or greater rise in IgG titer between an acute specimen and a convalescent specimen collected 2 to 4 weeks later. A single elevated titer never confirms acute infection, since 5% to 10% of healthy people carry reciprocal R. rickettsii IgG titers of 64 or more. PCR of blood or buffy coat can detect infection earlier but is limited by low circulating organism numbers, is blunted by prior doxycycline, and performs better on eschar swabs and biopsy tissue. Scrub typhus diagnosis combines IFA serology with PCR, since a single test is rarely definitive.¹⁸

Rickettsia prowazekii is an HHS select agent, so its identification, or credible suspicion of it, invokes the laboratory’s select-agent referral procedure.¹⁹

Ehrlichiosis and anaplasmosis

Ehrlichia and Anaplasma are small, tick-borne, obligately intracellular gram-negative coccobacilli that infect leukocytes and grow as intracytoplasmic clusters, morulae, visible on a Wright-Giemsa-stained smear.¹⁸

Careful smear review for morulae, ideally on a buffy-coat preparation, gives the fastest presumptive answer any laboratory can produce, and accompanying leukopenia and thrombocytopenia support the diagnosis. The smear is far more often positive in anaplasmosis than in E. chaffeensis ehrlichiosis, a negative smear never excludes either infection, and the infected cell type only suggests the agent. Toxic granulation, Döhle bodies, and platelets overlying a leukocyte are the recognized false-positive look-alikes. PCR of whole blood is the most sensitive routine method, best in the first week and diminished within about 48 hours of doxycycline. IFA serology confirms retrospectively through a fourfold rise between paired specimens; IgM alone is unreliable, and antibody is commonly absent during the acute illness, so serology never drives the treatment decision.¹⁸

Q fever

Coxiella burnetii is classified in the order Legionellales, near Legionella, and resembles the rickettsiae only clinically. It forms a spore-like small-cell variant highly resistant to heat, desiccation, and disinfectants. The organism persists in the environment and transmits by inhaled aerosols from birth products, dust, and animal products of infected livestock, and its infectious dose is very low. It is an HHS select agent and a CDC category B bioterrorism agent.^19-21

Acute Q fever is usually a self-limited febrile illness; chronic Q fever is, in nearly every case, C. burnetii endocarditis on a previously damaged valve. Diagnosis is serologic and turns on the organism’s two antigenic phases. Antibody against phase II antigen rises first and dominates acute infection. Sustained high-titer antibody against phase I antigen marks chronic infection: an anti-phase I IgG titer of 1:1024 or greater by IFA, with definite endocarditis or vascular infection, defines proven chronic Q fever, and a phase I IgG titer of 1:800 or greater serves as a major criterion in the modified Duke endocarditis framework. PCR of blood or serum outperforms serology during the first 1 to 2 weeks of acute illness, before seroconversion.^1,20

Bartonella infections

Bartonella species are fastidious, blood- and endothelium-tropic gram-negative bacteria transmitted by arthropod vectors from animal reservoirs. Primary isolation needs blood-enriched media and 5% CO₂ and takes 5 days to several weeks, so culture rarely makes the diagnosis.²

IFA serology is the standard first test, with two limits worth naming: titers start low in acute infection, so paired acute and convalescent specimens are often needed, and antibody cross-reacts between B. henselae and B. quintana and with Coxiella and Chlamydia species. PCR is far more sensitive on excised cardiac-valve tissue than on blood or serum in endocarditis. In the acute erythrocytic phase of Oroya fever, a Giemsa-stained blood smear shows red-violet organisms associated with red cells.^1,2

References

1. Liesman RM, Pritt BS, Maleszewski JJ, Patel R. Laboratory diagnosis of infective endocarditis. J Clin Microbiol. 2017;55(9):2599-2608. doi:10.1128/JCM.00635-17
2. Carroll KC, Pfaller MA, Landry ML, McAdam AJ, Karlowsky JA, Patel R, Pritt BS, eds. Manual of Clinical Microbiology. 13th ed. ASM Press; 2023.
3. Papp JR, Schachter J, Gaydos CA, Van Der Pol B. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae—2014. MMWR Recomm Rep. 2014;63(RR-2):1-19. Accessed August 29, 2026.
4. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70(RR-4):1-187. doi:10.15585/mmwr.rr7004a1
5. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 36th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute; 2026. Accessed August 29, 2026.
6. Tamma PD, Bonomo RA, Heil EL, Justo JA, Satlin MJ, Mathers AJ. IDSA 2026 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Infectious Diseases Society of America; 2026. Accessed August 29, 2026.
7. Oliver SE, Rubis AB, Soeters HM, et al. Epidemiology of invasive nontypeable Haemophilus influenzae disease—United States, 2008-2019. Clin Infect Dis. 2023;76(11):1889-1895. doi:10.1093/cid/ciad054
8. Potts CC, Rodriguez-Rivera LD, Retchless AC, et al. Antimicrobial susceptibility survey of invasive Haemophilus influenzae in the United States in 2016. Microbiol Spectr. 2022;10(3):e0257921. doi:10.1128/spectrum.02579-21
9. Morton AB, Vareechon C, Pettengill MA. Is beta-lactamase testing acceptably accurate for predicting Haemophilus influenzae susceptibility to beta-lactams? Epidemiological data from Philadelphia, USA, 2017-2023. Microbiol Spectr. 2023;11(5):e0129223. doi:10.1128/spectrum.01292-23
10. Centers for Disease Control and Prevention. Clinical guidance for typhoid fever. Accessed August 29, 2026.
11. Centers for Disease Control and Prevention. How Lyme disease spreads. Accessed August 29, 2026.
12. Centers for Disease Control and Prevention. Clinical testing and diagnosis for Lyme disease. Accessed August 29, 2026.
13. Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019;68(32):703. doi:10.15585/mmwr.mm6832a4
14. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep. 1995;44(31):590-591.
15. Centers for Disease Control and Prevention. About Southern tick-associated rash illness. Accessed August 29, 2026.
16. Centers for Disease Control and Prevention. Clinical guidance for soft tick relapsing fever (STRF). Accessed August 29, 2026.
17. Centers for Disease Control and Prevention. Leptospirosis. In: CDC Yellow Book: Health Information for International Travel. Accessed August 29, 2026.
18. Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis—United States. MMWR Recomm Rep. 2016;65(RR-2):1-44. doi:10.15585/mmwr.rr6502a1
19. Federal Select Agent Program. Select agents and toxins list. Accessed August 29, 2026.
20. Anderson A, Bijlmer H, Fournier PE, et al. Diagnosis and management of Q fever—United States, 2013: recommendations from CDC and the Q Fever Working Group. MMWR Recomm Rep. 2013;62(RR-3):1-30. Accessed August 29, 2026.
21. Centers for Disease Control and Prevention. Biological and chemical terrorism: strategic plan for preparedness and response: recommendations of the CDC Strategic Planning Workgroup. MMWR Recomm Rep. 2000;49(RR-4):1-14. Accessed August 29, 2026.