Ticks (Acari: Ixodidae and Argasidae) transmit multiple and diverse pathogens (including bacteria, protozoa, and viruses), which cause a wide range of human and animal diseases, including rickettsial diseases, caused by bacteria in the order Rickettsiales. Vertebrate animals play an integral role in the life cycle of tick species, whereas humans are incidental hosts. Awareness, diagnosis, and control of tickborne rickettsial diseases are most effectively addressed by considering the intersecting components of human, animal, and environmental health that collectively form the foundation of One Health (1), an approach that integrates expertise from multiple disciplines and facilitates understanding of these complex zoonoses. Tickborne rickettsial diseases in humans often share similar clinical features yet are epidemiologically and etiologically distinct. In the United States, these diseases include 1) Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii; 2) other spotted fever group (SFG) rickettsioses, caused by Rickettsia parkeri and Rickettsia species 364D; 3) Ehrlichia chaffeensis ehrlichiosis, also called human monocytic ehrlichiosis; 4) other ehrlichioses, caused by Ehrlichia ewingii and Ehrlichia muris-like (EML) agent; and 5) anaplasmosis, caused by Anaplasma phagocytophilum (2), also called human granulocytic anaplasmosis. Rickettsial pathogens transmitted by arthropods other than ticks, including fleas (Rickettsia typhi), lice (Rickettsia prowazekii), and mites (Rickettsia akari) are not included in this report. Imported tickborne rickettsial infections that might be diagnosed in returning international travelers are summarized; however, tickborne and nontickborne rickettsial illnesses typically encountered outside the United States are not addressed in detail in this report. Prophylaxis; start after mechanical bowel preparation the afternoon and evening before surgery 1 g PO q6-8hr for 3 doses 15 mg/kg IV over 30-60 min; complete approximately 1 hr before surgery; may administer 7.5 mg/kg IV over 30-60 min at 6 and 12 hr after initial dose for maintenance; discontinue within 12 hr after surgery Appetite loss Candidiasis Diarrhea Dizziness Headache Nausea Vomiting Ataxia Dark urine Disulfiram-type reaction with ethanol Furry tongue Hypersensitivity Neutropenia Metallic taste Neuropathy Pancreatitis Seizures Thrombophlebitis Xerostomia Encephalopathy Aseptic meningitis Optic neuropathy Stevens-Johnson syndrome Toxic epidermal necrolysis Decreased libido Hypersensitivity to metronidazole or other nitroimidazoles (although cautious desensitization has been applied) Pregnancy, 1st trimester in patients with trichomoniasis Use of disulfiram within past 2 weeks; use of alcohol during therapy or within 3 days of discontinuing therapy Seizures and aseptic meningitis reported with increase in dose and chronic therapy Cases of encephalopathy and peripheral neuropathy (including optic neuropathy) reported with metronidazole Encephalopathy reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria; CNS lesions seen on MRI described in reports of encephalopathy; CNS symptoms are generally reversible within days to weeks upon discontinuation of therapy; lesions seen on MRI have also been described as reversible Peripheral neuropathy, mainly of sensory type reported and characterized by numbness or paresthesia of an extremity Prescribing metronidazole tablets in absence of a proven or strongly suspected bacterial or parasitic infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria and parasites Superinfection may occur with prolonged use Severe hepatic impairment; administer lower doses with caution Use with caution; potential accumulation in end stage renal disease; supplemental doses may be needed in patients receiving hemodialysis Use with caution in history of heart failure, hepatic failure, H. pylori infection, renal impairment Use with care in patients with evidence of or history of blood dyscrasia; agranulocytosis, leukopenia and neutropenia have been associated with metronidazole administration; monitor complete blood count; monitor complete blood count (CBC) for leukopenia before, during, and after prolonged repeated therapy Avoid alcohol while taking medication and for at least three days after discontinuation Antiandrogen: May cause gynecomastia Known or previously unrecognized candidiasis may present more prominent symptoms during therapy and requires treatment with a candicidal agent Metronidazole injection, USP contains 790 mg of sodium per 100 m L; use care when administering injection to patients receiving a controlled sodium diet or corticosteroids or to patients predisposed to edema Severe neurological disturbances, including encephalopathy, cerebellar symptoms, convulsive seizures, and aseptic meningitis, reported in patients treated with metronidazole; advise patients to report neurologic symptoms that occur during metronidazole administration; discontinue metronidazole treatment if any abnormal neurologic symptoms occur such as ataxia, dizziness, confusion or any other CNS adverse reaction Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome reported with products containing metronidazole for systemic use; in this population, metronidazole should therefore be used after careful benefit-risk assessment and only if no alternative treatment available; obtain liver function tests prior to start of therapy, within first 2-3 days after initiation of therapy, frequently during therapy and after end of treatment; discontinue metronidazole if elevation of liver function occurs, and monitor liver function tests until baseline values are reached; advise patients with Cockayne syndrome to stop taking metronidazole immediately if they experience any symptoms of potential liver injury, such as abdominal pain, nausea, change in stool color or jaundice, and to contact their healthcare provider When metronidazole tablets are prescribed to treat a bacterial infection, patients should be told that the medication should be taken exactly as directed; skipping doses or not completing full course of therapy may decrease effectiveness of immediate treatment and increase likelihood that bacteria will develop resistance and will not be treatable by metronidazole tablets in the future There are no adequate and well-controlled studies of in pregnant women; there are published data from case-control studies, cohort studies, and 2 meta-analyses that include more than 5000 pregnant women who used metronidazole during pregnancy; many studies included first trimester exposures; one study showed increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in utero; however, these findings were not confirmed Metronidazole crosses placental barrier and its effects on human fetal organogenesis are not known; reproduction studies have been performed in rats, rabbits and mice at doses similar to maximum recommended daily dose based on body surface area comparisons; there was no evidence of harm to fetus due to metronidazole; healthcare provider should carefully consider potential risks and benefits for each specific patient before prescribing therapy Metronidazole is present in human milk at concentrations similar to maternal serum levels, and infant serum levels can be close to or comparable to infant therapeutic levels Because of potential for tumorigenicity shown for metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account importance of drug to mother; alternatively, a nursing mother may choose to pump and discard human milk for duration of metronidazole therapy, and for 24 hours after therapy ends and feed her infant stored human milk or formula There are published data from case-control studies, cohort studies, and 2 meta-analyses that included more than 5000 pregnant women who used metronidazole systemically during pregnancy Many studies included first trimester exposures One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in utero; however, these findings were not confirmed In addition, more than 10 randomized, placebo-controlled clinical trials that together enrolled over 5000 pregnant women assessed the possible effect of systemic antibiotic treatment (including with metronidazole) for bacterial vaginosis on the incidence of preterm delivery; most studies did not show an increased risk of congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy Three studies conducted to assess the risk of infant cancer following systemic metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited Some drugs may be incompatible with reconstituted solution from powder (which contains metronidazole HCl) but compatible with RTU IV solution (which contains metronidazole), and vice versa Additive: Aztreonam, cefepime(? ), ciprofloxacin (may be compatible with RTU solution), dopamine, meropenem Y-site: Amphotericin B cholesteryl sulfate, aztreonam, filgrastim, meropenem, warfarin Reconstitute powder with 4.4 m L sterile water for injection, bacteriostatic water for injection, NS, or bacteriostatic NS to a final concentration of 100 mg/m L (p H 0.5-2) Further dilute in glass or plastic container to no more than 8 mg/m L with NS, D5W, or LR Neutralize with approximately 5 m Eq Na HCO3 per 500 mg metronidazole; final p H 6-7 No dilution or buffering necessary for ready-to-use IV solution The above information is provided for general informational and educational purposes only. 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