Version May 2024
INTRODUCTION — Linezolid is a synthetic oxazolidinone with bacteriostatic activity against gram-positive organisms [1]. Tedizolid is a newer drug in the same class with comparable spectrum of activity but with limited US Food and Drug Administration-approved indications. Longer-term use of these drugs has been limited by concern for adverse effects.
This topic will review issues related to the clinical use of linezolid and tedizolid. The clinical indications in which the drug may be used are discussed separately in the appropriate topic reviews.
SPECTRUM AND INDICATIONS — Linezolid and tedizolid demonstrate activity in vitro against a variety of gram-positive bacteria including streptococci, enterococci (including vancomycin-resistant enterococci [VRE]), coagulase-negative staphylococci, methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Bacillus species, Corynebacterium species, and Listeria monocytogenes [2-9].
Linezolid and tedizolid demonstrate activity in vitro against several Mycobacterium spp, including both Mycobacterium tuberculosis and nontuberculous mycobacterium [10-15]. In addition, linezolid and tedizolid are active in vitro against numerous Nocardia spp [16-18]. Linezolid abolishes toxin production and reduces sporulation in Bacillus anthracis in vitro; therefore, it is a treatment option for select infections due to anthrax [19,20].
Linezolid is approved by the US Food and Drug Administration (FDA) for treatment of adults and children with pneumonia (nosocomial and community-acquired) and skin and skin structure infections (complicated and uncomplicated), including those due to MRSA and VRE [21,22]. (See "Acute cellulitis and erysipelas in adults: Treatment" and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections" and "Treatment of enterococcal infections".)
Clinical experience with use of linezolid for other forms of infections due to MRSA and VRE has been described, including bacteremia and osteomyelitis [23]. In addition, linezolid has been used for treatment of mycobacterial infections and nocardial infections. (See "Treatment of drug-resistant pulmonary tuberculosis in adults" and "Overview of nontuberculous mycobacterial infections".)
Tedizolid is approved by the FDA for treatment of adults and children ≥12 years with complicated and uncomplicated skin and skin structure infections. Data from randomized trials suggest tedizolid is noninferior to linezolid for the treatment of acute bacterial skin and soft tissue infections [24,25].
MECHANISM OF ACTION — Linezolid and tedizolid are bacteriostatic oxazolidinones that inhibit initiation of bacterial protein synthesis at the 50S ribosome. The 50S subunit contains 5S rRNA, 23S rRNA, and 34 proteins [4-6,26,27]. These agents also suppress production of bacterial toxins such as Panton-Valentine leukocidin, alpha-hemolysin, and toxic shock syndrome toxin-1 [28-30].
RESISTANCE — Among staphylococci, linezolid resistance appears to occur most frequently among coagulase-negative staphylococci isolates, mainly Staphylococcus epidermidis [31]. However, S. aureus linezolid resistance, while infrequent, has also been described [32-36].
Vancomycin-resistant enterococci with linezolid resistance has also been described [37]. Resistance in enterococci is also infrequent, occurring in <1 percent of isolates in large surveillance studies [38]. Resistance to linezolid typically occurs through multiple mutations of the 23S rRNA genes [39].
Resistance also can emerge from mutations or by acquisition from other organisms [40].
●A mobile gene, cfr, encoding a methyltransferase that modifies 23S rRNA (causing failure of linezolid binding to its bacterial target site, conferring resistance) has been identified in staphylococci [41-43] and in enterococci [44,45].
In vitro data demonstrating retained tedizolid activity against cfr isolates suggest this may be an effective alternative agent against some linezolid-resistant pathogens, most notably S. aureus [46-48]. Such isolates, although susceptible, may also demonstrate increases in tedizolid minimum inhibitory concentration (MIC) [48].
●Other plasmid-borne resistant determinants, optrA and poxtA, encode ribosomal protection factors leading to increased MICs for linezolid and tedizolid [45,49,50]. In one study including 154 linezolid-resistant Enterococcus isolates (Enterococcus faecium and Enterococcus faecalis), 26.3 percent of isolates carrying the poxtA-encoding plasmid also harbored the vanA gene [50].
PHARMACOKINETICS AND PHARMACODYNAMICS
General principles — The systemic absorption of linezolid approaches 100 percent following oral administration [51]. Linezolid binds poorly to serum proteins (31 percent). Therefore, it penetrates well into most body compartments (including bone, alveoli, and the cerebrospinal fluid) [51]. As a result, linezolid has a volume of distribution that is similar to total body water (30 to 50 L). The overall tissue distribution of linezolid is stable and is not adversely affected by sepsis or peripheral vascular disease or obesity [52-58]. The drug undergoes hepatic oxidative metabolism into two inactive metabolites eliminated predominantly in the urine [52]. Linezolid has an elimination half-life of four hours [1].
Tedizolid phosphate (a prodrug) is rapidly converted by phosphatases to the active form of tedizolid after oral or intravenous administration. Similar to linezolid, bioavailability following oral administration is high (approximately 90 percent). In contrast to linezolid, tedizolid is highly bound to plasma proteins (70 to 90 percent). It is extensively distributed (with a volume of distribution of 67 to 80 L). Elimination as inactive sulfate conjugate occurs via the liver, with <3 percent of the dose excreted in feces and urine as unchanged drug [59,60].
Based largely on in vitro modeling, the antimicrobial effectiveness of both linezolid and tedizolid is best predicted by the ratio of the 24-hour area under the time-concentration curve to minimum inhibitory concentration (MIC) [52,61]. Based on these targets, simulations examining target attainment suggest that isolates with an MIC ≥2 mcg/mL may not respond to standard dosing [59,62,63]. Linezolid displays moderate postantibiotic effects against S. aureus [64].
Children — In general, the clearance of linezolid in children is influenced by age, weight, and renal function [65-67]. In studies of linezolid in children with critical illness, drug clearance correlated directly with body weight and inversely with aspartate aminotransferase [68]. While clearance in newborns is comparable with clearance in adults, children <12 years of age exhibit more rapid clearance than adults [69].
Published data for tedizolid pharmacokinetics in pediatric patients are limited to adolescents and were generally comparable with parameters seen in adult patients [70].
Other populations — Significant variability in linezolid trough concentrations have been reported in hospitalized patients [62]. Patients >80 years of age and those with renal dysfunction have demonstrated elevated trough concentrations [71]. In contrast, critical care patients and those with cystic fibrosis or major burns may be at increased risk of subtherapeutic exposure with standard dosing. Pharmacokinetic studies also indicate altered pharmacokinetics of linezolid in patients with obesity and hepatic dysfunction. (See 'Dosing and administration' below and 'Serum concentration monitoring' below.)
Tedizolid pharmacokinetics are not altered in older adult patients [72] or in patients with cystic fibrosis [73].
DOSING AND ADMINISTRATION
General principles — Linezolid may be given orally or parenterally. The adult dose is 600 mg intravenously or orally twice daily [74]. A reduced oral dose (linezolid 400 mg twice daily) can be administered for uncomplicated skin and skin structures in adult patients. The pediatric dose is 10 mg/kg intravenously or orally either every 8 hours (≤12 years of age) or every 12 hours (>12 years of age).
Linezolid 600 mg to 1200 mg daily has been evaluated for treatment of drug-resistant tuberculosis as part of combination therapy (often bedaquiline and pretomanid, with or without moxifloxacin) [75-77].
Tedizolid may be given orally or parenterally as a single daily dose of 200 mg. It is US Food and Drug Administration approved for patients >12 years of age.
Renal insufficiency — No dose adjustments are recommended for patients with renal insufficiency based on the product monograph. However, renal impairment leads to accumulation of linezolid and its metabolites, and observational data has demonstrated increased risk of thrombocytopenia in patients with renal insufficiency [78,79].
Use of serum drug concentration monitoring with dose adjustment may be useful in patients with renal insufficiency [80,81]. (See 'Serum concentration monitoring' below.)
Hepatic insufficiency — Despite reductions in linezolid clearance in patients with cirrhosis [82], dose adjustments for linezolid and tedizolid are not recommended for patients with hepatic insufficiency.
Use of ECMO — Reduced serum concentrations of linezolid have been observed in patients undergoing extracorporeal membrane oxygenation (ECMO) while receiving standard dosing [83-85]. Use of serum drug concentration monitoring with dose adjustment may be useful in such cases. (See 'Serum concentration monitoring' below.)
Obesity — Standard linezolid dosing may be inadequate for patients who are overweight and patients with obesity [86,87]. In such cases, some favor that linezolid dose adjustments be based on creatinine clearance (estimated utilizing the Chronic Kidney Diseases Epidemiology formula [CrCLCKD-EPI]), rather than based on weight (using body mass index or total body weight) [87]. For patients ≥140 kg with invasive infection due to pathogen with a minimum inhibitory concentration ≥2 mcg/mL in the setting of weight ≥140 kg and CrCLCKD-EPI ≥60 mL/min/1.73 m2, dose escalation (up to 450 mg every 8 hours) may be appropriate.
Duration of treatment — Linezolid and tedizolid are licensed for a maximum treatment duration of 28 days and 6 days, respectively. Excluding its use in mycobacterial infections, clinical studies have reported efficacy and safety data on the use of linezolid for periods beyond 28 days. Only limited data are available to determine the safety of tedizolid for extended periods [88-90].
Coadministration with other agents — When possible, patients on serotonergic agent(s) who require linezolid or tedizolid should discontinue the serotonergic agent at least two weeks prior to beginning oxazolidinone therapy (table 1). However, this approach is not practical for management of acute bacterial infection. (See 'Serotonin syndrome' below.)
Patients on linezolid or tedizolid should avoid tyramine-containing foods (table 2).
PREGNANCY AND BREASTFEEDING — Data on use of linezolid and tedizolid in pregnancy and breastfeeding are limited.
Studies of linezolid in animals have revealed adverse fetal effects (decreased fetal body weight and increased incidence of fusion of costal cartilages) [91]. However, there are no controlled studies in pregnant women. Linezolid and tedizolid should be given to pregnant women only if the potential benefits justify the potential risk to the fetus.
Linezolid concentrations in breast milk are similar to maternal serum concentrations. If linezolid is required by the mother, it is not a reason to discontinue breastfeeding. However, because there is no published experience with linezolid during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant [92].
It is unknown whether tedizolid is excreted in human breast milk [60].
ADVERSE EFFECTS
General principles — In general, safety concerns have limited widespread and extended use of linezolid. The most significant adverse effects include gastrointestinal symptoms, myelosuppression (most commonly thrombocytopenia), neuropathy (peripheral and optic), and lactic acidosis [93-95]. Less frequently observed adverse effects include hepatotoxicity, hypoglycemia, and syndrome of inappropriate antidiuretic hormone secretion [1,96].
Risk factors for adverse effects (notably peripheral neuropathy and myelosuppression) secondary to linezolid administration appear to be both dose and duration related [75,97]. In clinical trials utilizing linezolid 1200 mg/d (as part of combination therapy) for drug-resistant tuberculosis, peripheral neuropathy and myelosuppression developed in 81 percent and 48 percent of study subjects (respectively) [76]. In contrast, rates were substantially lower (24 percent and 13 percent, respectively) when lower doses (600 mg/d) were utilized [75].
Data on tedizolid at higher doses for extended periods are limited. In one report of 60 patients receiving tedizolid for a mean length of 27 days, most (72 percent) finished the course [88]. Another reported tedizolid use for longer durations (median treatment duration of 29 days [interquartile range -IQR- 15 to 44]) in 51 patients for the treatment of osteoarticular infections [90].
Tedizolid has been associated with myelosuppression [98] and neuropathy. Use and experience with tedizolid is limited compared with that of linezolid. Emerging data also suggests the risk of lactic acidosis or serotonin syndrome may be similar with tedizolid as with linezolid [1,99].
Available studies comparing adverse effects linezolid and tedizolid include the following:
●In a randomized trial including patients with acute bacterial skin and skin infections treated with tedizolid (200 mg orally once daily for 6 days) or linezolid (600 mg orally every 12 hours for 10 days), the most frequent adverse effects were nausea (8.5 versus 13.4 percent), headache (6.3 versus 5.1 percent), and diarrhea (4.5 versus 5.4 percent) [24].
●In a randomized trial including patients with pneumonia on mechanical ventilation treated with tedizolid (200 mg IV once daily for 7 days) or linezolid (600 mg IV every 12 hours for 10 to 14 days), the most frequent adverse effects were anemia (0.6 versus 1.1 percent), thrombocytopenia (0.6 versus 0.8 percent), and diarrhea (1.7 versus 5.5 percent), respectively [100].
●A retrospective review of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database included 271 and 11,259 adverse events due to tedizolid and linezolid respectively. No difference in the odds of pancytopenia, peripheral neuropathy, serotonin syndrome, and lactic acidosis were observed between oxazolidinones [99].
Myelosuppression — Linezolid has been associated with suppression of all blood cell lineages; the incidence is less than 1 percent and is generally dependent on dose and duration of treatment [101]. Thrombocytopenia (<100,000 platelets/microL) is the most common presentation of linezolid-induced myelosuppression [102].
Risk factors for linezolid-induced myelosuppression include low baseline blood cell counts, renal impairment, and duration of linezolid therapy ≥14 days [78,93,101-106]. Monitoring for myelosuppression during linezolid administration is discussed below. (See 'Monitoring' below.)
Count recovery typically occurs within one to three weeks after discontinuation of linezolid [101,107].
There are no known effective measures for prevention of linezolid-induced myelosuppression. Use of pre-emptive pyridoxine was not associated with prevention of myelosuppression in one study including 24 patients treated with a prolonged course of linezolid [108]. The time to recovery varies with the cell line and degree of suppression [101].
Data comparing the incidence and severity of linezolid-induced thrombocytopenia with that of tedizolid come primarily from trials for treatment of skin and skin structure infections. In these studies, the incidence of tedizolid-associated myelosuppression was similar or lower to that observed with linezolid [109,110].
Neuropathy — Oxazolidinones have been associated with peripheral neuropathy and optic neuropathy; these effects are time and dose dependent and their incidence is unknown [99,111-114]. The reported duration of use prior to development of neuropathy is 5 to 11 months [115]. The mechanism of neural toxicity is uncertain. Possibilities include impairment of mitochondrial protein synthesis or direct toxic effects [115-117].
Peripheral neuropathy typically presents as a "glove and stocking" sensory impairment. Nerve conduction studies demonstrate a sensory-motor axonal pattern [111,118]. Optic neuropathy presents with diminished visual acuity, development of scotomas, and diminished color perception [112,115].
Oxazolidinones should be discontinued in patients with peripheral or optic neuropathy. There is no specific treatment for oxazolidinones-induced neuropathy.
Optic neuropathy may be reversible. In one report including two patients with linezolid-induced optic neuropathy, visual function gradually recovered three to four months after drug discontinuation [119]. Peripheral neuropathy may be irreversible in some cases [115,120].
Lactic acidosis — Between 2011 and 2016, 90 cases of lactic acidosis associated with linezolid use were reported to the US Food and Drug Administration [121]. Between 2014 and 2020, 154 cases of lactic acidosis due to linezolid and 4 cases due to tedizolid were reported to the US Food and Drug Administration [99]. Lactic acidosis appears to occur more frequently in the setting of prolonged linezolid administration (40 to 50 days) [122]. The mechanism may be attributable to mitochondrial toxicity, given the similarity between human mitochondrial 16S RNA and bacterial 23S rRNA [95,123].
Onset of oxazolidinones-associated lactic acidosis may be 1 to 16 weeks after drug initiation [99,120]. Clinical manifestations may be nonspecific and include abdominal pain, nausea, vomiting, and generalized weakness, in the setting of low serum bicarbonate concentration. Such manifestations should prompt measurement of serum lactate concentration [122].
Oxazolidinones should be discontinued in patients with lactic acidosis [94,95]. Oxazolidinones-induced lactic acidosis has a mortality rate of 25 to 50 percent [99,124]. In patients who recover, lactate levels generally normalize in 2 to 14 days [122]. Issues related to management of lactic acidosis are discussed separately. (See "Approach to the adult with metabolic acidosis" and "Approach to the child with metabolic acidosis".)
DRUG INTERACTIONS — Administration of linezolid with concomitant serotonergic agents (notably selective serotonin-reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs]) or agents inhibiting monoamine oxidase have been associated with serotonin syndrome. (See 'Serotonin syndrome' below.)
Linezolid does not interact with the cytochrome P450 oxidative system. Inducers of CYP3A may increase the clearance of linezolid. Concomitant administration of agents that either induce (eg, rifampin, levothyroxine) or inhibit (eg, clarithromycin, select proton pump inhibitors) p-glycoprotein may decrease or increase linezolid concentrations, respectively.
Coadministration of linezolid with warfarin may be associated with increased prothrombin time; the mechanism is not known [62,125].
Plasma concentrations of oral Breast Cancer Resistance Protein (BCRP) substrates may be increased by coadministration with oral tedizolid due to its inhibition of BCRP in the intestine [60]. Coadministration of tedizolid with BCRP substrates with a narrow therapeutic index (such as methotrexate or topotecan) should be avoided if possible.
Concomitant use of linezolid may enhance the hypertensive effect of either directly and indirectly acting sympathomimetic agents (such as pseudoephedrine, epinephrine, norepinephrine) and dopaminergic agents (eg, dopamine, dobutamine).
Additional information on drug interactions may be found using the drug interactions tool within UpToDate.
Serotonin syndrome — Linezolid can reversibly inhibit monoamine oxidase (MAO). Coadministration of linezolid with nonselective MAO inhibitors, SSRIs, SNRIs, or bupropion can precipitate serotonin toxicity (table 1) [1,126-130]. Similarly, ingestion of tyramine-containing foods can cause hypertensive crisis or serotonin syndrome (table 2) [1,131]. (See "Serotonin syndrome (serotonin toxicity)".)
Estimates of risk of serotonin syndrome resulting from concomitant use of linezolid and other serotonergic agents range from 0.2 to 1 percent [1,131-135]. The highest risk appears to be in combination with higher linezolid doses and/or >2 serotonergic agents and/or specific agents (such as citalopram, escitalopram, MAO-Is, and methadone).
The US Food and Drug Administration has warned that linezolid should be used in patients taking SSRIs or SNRIs only when absolutely needed [136]. If linezolid is required, the serotonergic medication should be stopped at least two weeks in advance of linezolid treatment, if feasible. However, abrupt withdrawal of SSRIs or SNRIs can be problematic due to concern for withdrawal. In such situations, dose reduction may be an acceptable alternative. While concomitant use of linezolid with an SSRI or SNRI is not absolutely contraindicated, patients receiving serotonergic agents while receiving linezolid should be monitored closely. Patients receiving concomitant therapy should be educated regarding the signs and symptoms of serotonin syndrome.
Clinical manifestations of serotonin syndrome include a broad range of symptoms, from mild tremor to life-threatening hyperthermia and shock. Onset of symptoms may be hours to days following coadministration of linezolid with serotonergic agents and may include tachycardia, hypertension, hyperthermia, agitation, tremor, myoclonus, hyperreflexia, muscle rigidity, dilated pupils, dry mucus membranes, increased bowel sounds, flushed skin, and diaphoresis. Diagnostic criteria are discussed separately [137]. (See "Serotonin syndrome (serotonin toxicity)".)
The approach to management depends on the severity of illness. In patients with severe serotonergic syndrome, all serotonergic agents should be discontinued. Other aspects of management for serotonin syndrome are discussed further separately. (See "Serotonin syndrome (serotonin toxicity)".)
Symptoms usually resolve within 24 hours of drug discontinuation and initiating care, but drugs with long durations of action or active metabolites may cause prolonged symptoms.
Tedizolid exhibits weak and reversible MAO inhibition [138]. Therefore, the potential for serotonin syndrome is thought to be less than linezolid. In addition, patients at increased risk of serotonin syndrome were specifically excluded from phase 2 and 3 trials of tedizolid. And early published experience with tedizolid was restricted to shorter courses of therapy than linezolid.
Descriptions of prolonged tedizolid therapy for the management of "off-label" indications (such as nontuberculous mycobacterial infections) have been reported [89,99,139,140]. These retrospective reports generally involve a limited number of patients. Between 2014 and 2020, 369 cases of serotonin syndrome due to tedizolid were reported to the US Food and Drug Administration (FDA) [99].
MONITORING
Clinical monitoring — For patients receiving linezolid longer than 28 days, routine ophthalmologic and neurologic assessment should be performed [106].
Patients on serotonergic agents who are receiving linezolid or tedizolid should be monitored for signs and symptoms of serotonin syndrome.
Laboratory monitoring — For patients receiving linezolid or tedizolid for longer than seven days, routine laboratory monitoring includes weekly complete blood count, basic metabolic panel, and liver function panel [102].
In addition, twice-weekly blood count monitoring is warranted for patients with underlying myelosuppression or receiving other potentially myelosuppressive medications.
Serum concentration monitoring
●To reduce toxicity – Serum concentration monitoring of linezolid has been proposed as a potential strategy to reduce toxicity, notably thrombocytopenia [80,141-144]. Serum concentration monitoring may be most useful in patients with high interpatient variability in serum concentrations. These include patients with renal impairment or augmented renal clearance, patients on renal replacement therapy, patients receiving high doses and/or prolonged linezolid therapy (>28 days), children, patients with severe hepatic insufficiency, patients receiving multiple concomitant interacting medications (including clarithromycin, proton pump inhibitors, amiodarone, amlodipine, calcium channel blockers, rifampin, phenobarbital, and levothyroxine), patients with low baseline platelet counts, and patients with extremes of body weight.
However, the role of routine serum concentration monitoring of linezolid is hampered by lack of established peak and trough targets, and absence of a readily available assay. For patients who do undergo linezolid serum concentration monitoring, target serum trough concentrations of 2 to 8 mcg/mL are suggested.
The above approach is supported by a retrospective study including 108 patients (including 21 patients with eGFR ≤60 mL/min) who underwent linezolid therapeutic drug monitoring, lower rates of treatment failure (due to toxicity or persistent infection) were observed among patients who monitored (14 versus 64 percent) [80,144].
●To enhance efficacy – The benefits of monitoring to enhance efficacy have not been established, since optimal exposures based on pharmacokinetic/pharmacodynamic targets may vary with pathogen and site of infection. Thus far, clinical trial data for tedizolid have not established a relationship between drug exposure and clinical response [100,145].
Limited clinical data have been published to define optimal efficacy targets for most pathogens. Dose titrations may further be limited by the lack of commercially available dosage forms to provide the desired amount.
SUMMARY
●Linezolid is a synthetic oxazolidinone with bacteriostatic activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Tedizolid is a newer drug in the same class with comparable spectrum of activity. Use of these drugs has been limited by cost and concern for adverse effects. In general, they are reserved for patients who do not respond to or cannot tolerate other agents. (See 'Spectrum and indications' above.)
●Linezolid and tedizolid are bacteriostatic oxazolidinones that inhibit initiation of bacterial protein synthesis at the 50S ribosome. These drugs also suppress production of bacterial toxins. Linezolid failure and resistance have been described. (See 'Mechanism of action' above and 'Resistance' above.)
●Linezolid and tedizolid may be administered orally or intravenously. Both drugs exhibit high oral bioavailability and do not require dosing adjustment in patients with hepatic or renal dysfunction. Ideally, patients on serotonergic agent(s) (table 1) who require linezolid or tedizolid should discontinue the serotonergic agent at least two weeks prior to beginning oxazolidinone therapy and avoid tyramine-containing foods (table 2). (See 'Dosing and administration' above.)
●Safety concerns limit use of linezolid, particularly for extended durations. Adverse effects include myelosuppression, neuropathy (peripheral and optic), and lactic acidosis. (See 'Adverse effects' above.)
•Linezolid-associated myelosuppression can involve suppression of one or more blood cell lineages; it is typically mild and reversible. Thrombocytopenia (<100,000 platelets/microL) is the most common presentation. Risk factors include low baseline blood cell counts, renal impairment, and duration of linezolid therapy ≥14 days. Management consists of drug discontinuation and supportive care. (See 'Myelosuppression' above.)
•Linezolid has been associated with peripheral neuropathy and optic neuropathy. The neuropathic effects are time and dose dependent. Peripheral neuropathy typically presents as a "glove and stocking" sensory impairment. Optic neuropathy presents with diminished visual acuity, development of scotomas, and diminished color perception. Management consists of drug discontinuation. (See 'Neuropathy' above.)
•The likelihood of linezolid-associated lactic acidosis increases with the duration of administration. Clinical manifestations may be nonspecific and include abdominal pain, nausea, vomiting, and generalized weakness, in the setting of low serum bicarbonate concentration. Management consists of drug discontinuation and supportive care. (See 'Lactic acidosis' above and "Approach to the adult with metabolic acidosis" and "Approach to the child with metabolic acidosis".)
●Concomitant administration of linezolid with serotonergic agents (table 1) has been associated with serotonin syndrome. Clinical manifestations include a broad range of symptoms, from mild tremor to life-threatening hyperthermia and shock. The management approach depends on the illness severity. In patients with mild symptoms, clinicians must weigh risks and benefits when determining whether to continue coadministration of linezolid with serotonergic agents. Patients who require continuation of serotonergic agents should receive linezolid only if no other antimicrobial therapies are available; in such cases, patients should be monitored closely. (See 'Serotonin syndrome' above and "Serotonin syndrome (serotonin toxicity)".)
●Tedizolid has been associated with myelosuppression and neuropathy. Its association with serotonin syndrome is weak and includes patients treated with prolonged therapy. (See 'Adverse effects' above and 'Drug interactions' above.)
●For patients receiving linezolid or tedizolid for longer than seven days, routine laboratory monitoring includes weekly complete blood count, basic metabolic panel, and liver function panel. For patients with underlying myelosuppression or receiving other potentially myelosuppressive medications, twice-weekly blood count monitoring is warranted. For patients receiving linezolid longer than 28 days, routine ophthalmologic and neurologic assessment should be performed. (See 'Monitoring' above.)
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