Chloramphenicol is a synthetic broad-spectrum antibiotic. It was first mass-produced in the United States in 1949 and introduced into clinical practice (1). The drug is primarily metabolized in the liver, and its metabolites are excreted renally. Known adverse effects of chloramphenicol include bone marrow suppression, neuritis, toxic psychosis, hepatic injury, gray baby syndrome, myocardial toxicity, and severe cardiac dysfunction (2). Particularly in children, chloramphenicol use should be reserved for severe infections and given only when less toxic antibiotics are ineffective or contraindicated (3). Infants receiving excessive doses of chloramphenicol are at risk of fatal cardiovascular collapse, a condition known as gray baby syndrome (4–7) with a mortality rate as high as 40% (8). Although rarely reported in the past decade, gray baby syndrome persists in some resource-limited regions. Herein, we report a case of gray baby syndrome and review the literature to summarize the clinical characteristics, diagnosis, and management of this condition with the aim of facilitating timely clinical recognition and management by healthcare providers.

A 14-month-old boy (10 kg) of Yi ethnicity presented to the emergency department on September 22, 2023. He had accidentally ingested 1.5 g chloramphenicol (6 × 0.25 g tablets) left on the coffee table by his grandmother, which manifested as acute abdominal pain, vomiting, progressive lethargy, and coma within 3 h. At the time of admission, he showed hemodynamic instability (HR: 179 /min, BP: 87/50 mmHg, CRT: 4 s), hypothermia (36.3°C), and depressed consciousness (GCS 8). Laboratory investigations revealed severe metabolic acidosis (pH: 7.131, lactate: 10.06 mmol/L), anemia (Hb: 82 g/L), and hepato-renal impairment (ALT: 627 U/L, AST: 1,044 U/L, uric acid: 669 μmol/L), accompanied by cardiotoxicity (EF: 38%) and a critically elevated serum chloramphenicol level (92 μg/mL), confirming chloramphenicol-induced gray baby syndrome. Despite initial gastric lavage and fluid resuscitation, clinical deterioration necessitated pediatric intensive care unit admission. Aggressive management included mechanical ventilation, inotropic support (dopamine/milrinone), norepinephrine infusion, and high-dose vitamin C/B₁. Given delayed presentation (>8 h after ingestion) with established multiorgan failure, continuous renal replacement therapy (CRRT) was initiated at 18 h after ingestion for 79 h, alongside hepatoprotective agents (glutathione/bifendate). Hemodynamic stability was achieved within 4 h (EF 48%), and metabolic acidosis resolved by 10 h (lactate: 2.72 mmol/L). Key laboratory and diagnostic findings in this case are summarized in Table 1. After 3 weeks of intensive care, all laboratory and cardiac parameters normalized. The patient was discharged on October 14, 2023, with no sequelae observed during a 20-month follow-up (last assessment May 28, 2025), showing successful reversal of severe chloramphenicol toxicity through multimodal critical care intervention.

In 1960, the Massachusetts Medical Society (4) recommended the following chloramphenicol dosing regimens: infants over 30 days old: 100 mg/kg per day; full-term neonates: 50 mg/kg per day; and preterm infants under 30 days old: 25 mg/kg per day. The risk of toxicity is relatively low when serum chloramphenicol concentrations remain within the therapeutic range of 15–25 μg/mL (2). Gray baby syndrome is associated with serum concentrations exceeding 50 μg/mL (9). The characteristic clinical presentation includes hypotonia, lethargy, ashen-gray skin discoloration, cyanosis, abdominal distension, impaired peripheral perfusion, hypotension, hypothermia, and metabolic acidosis (4–7, 10). Notably, metabolic acidosis is regarded as an early indicator of chloramphenicol toxicity (11).

Chloramphenicol overdose inhibits mitochondrial protein synthesis, which disrupts oxidative phosphorylation and causes cellular necrosis. Necrosis releases vasoactive substances, triggering microcirculatory dysfunction (12). At high doses, the drug also induces myocardial damage and dysfunction (13), thus reducing cardiac output and hepatic blood flow, further impairing drug clearance and exacerbating toxicity. Newborns, particularly preterm infants, have underdeveloped livers and relatively low glucuronidation capacity, making them highly susceptible to chloramphenicol toxicity and the highest-risk group for gray baby syndrome (7). However, with excessive chloramphenicol dosing, similar symptoms can occur even in older children and adults (11, 14–16). Although the 1960 guidelines (4) significantly reduced the incidence of chloramphenicol toxicity, cases still occasionally occur due to prescription errors or accidental ingestion.

A total of 19 cases of chloramphenicol-induced gray baby syndrome have been reported in PubMed and Wanfang Database as of May 20, 2025 (Table 2). Among them, 10 were male, 5 were female, and the sex was not mentioned in 4 cases. Infants under 1 year of age constituted 13/19 (68.4%) of the cohort. The remaining cases included 3 adolescents, 1 adult, and 2 patients with unreported age. At the onset of gray baby syndrome symptoms, the cumulative chloramphenicol dose ranged from 95 mg/kg to 4,900 mg/kg. Serum chloramphenicol levels in these patients ranged from 30 μg/mL to 313 μg/mL. Notably, serum chloramphenicol levels exceeded 50 μg/mL in all patients except one (30 μg/mL). Herein, 11 of 17 cases with reported outcomes survived (64.7%), whereas the remaining 6 died (35.3%). The clinical manifestations observed in the present case, including vomiting, lethargy, pallor, impaired peripheral perfusion, respiratory distress, metabolic acidosis, reduced cardiac ejection fraction, ventricular dilation, and hepatomegaly, are consistent with the classic presentation of gray baby syndrome described in previous reports.

Among the 19 reported gray baby syndrome cases, 15 occurred in the United States and 4 in China. The US cases were predominantly concentrated within the first four decades since chloramphenicol's introduction into the market (13/15, 87%), with most of these cases reported from relatively economically developed urban areas. This geographic pattern may be attributable to greater accessibility to chloramphenicol in affluent regions at that time. Reports of chloramphenicol-induced gray baby syndrome have subsequently declined, coinciding with the introduction and widespread adoption of newer antibiotics. Conversely, all Chinese cases were reported after the year 2000 and originated exclusively from non- tier- one cities. In China, the Guidelines for Clinical Use of Antimicrobial Agents issued by the National Health Commission (formerly the Ministry of Health) in 2004 and 2015 both state that the clinical use of chloramphenicol has declined significantly due to increasing bacterial resistance and serious adverse effects such as bone marrow suppression. Nevertheless, chloramphenicol retains specific clinical indications owing to its excellent tissue penetration—including across the blood- brain and blood- ocular barriers—and its efficacy against intracellular pathogens such as Salmonella typhi and Rickettsia. The guidelines emphasize the necessity of regular blood- count monitoring during treatment. Chloramphenicol is contraindicated in premature and newborn infants because of the risk of gray baby syndrome, and therapeutic drug monitoring is required when its use in infants and young children is unavoidable (25, 26). However, in certain less- developed regions of China, inappropriate use of chloramphenicol in specific populations remains a concern due to its low cost and easy accessibility, which increases the risk of accidental ingestion by children or inappropriate prescribing by clinicians. Therefore, it must be strongly emphasized that chloramphenicol should be strictly avoided in children unless a clear clinical indication exists.

In addition, chloramphenicol use requires particular caution in children with severe malnutrition, hepatic impairment, or underlying cardiac disease as impaired drug clearance in these populations increases the risk of toxicity. In such high-risk patients, close monitoring of serum drug concentrations and vigilant assessment for signs of toxicity are essential (20, 27). For parents, ensuring that chloramphenicol is properly stored and kept out of reach is essential to prevent accidental ingestion by young children.

For patients suspected as having gray baby syndrome, serum chloramphenicol levels should be monitored if feasible. Imaging studies should encompass echocardiography, and electrocardiogram (ECG) is also indicated. Management of gray baby syndrome focuses on increasing chloramphenicol elimination and providing supportive care. Prompt removal of unabsorbed drug may involve induction of emesis, gastric lavage, or administration of cathartics. For absorbed drug clearance, aggressive IV fluid resuscitation and diuresis promote excretion; extracorporeal purification (e.g., CRRT and charcoal hemoperfusion) is considered for severe cases. Hemodynamic instability requires vigorous fluid resuscitation, supplemented with inotropes/vasopressors in cases of circulatory failure. Respiratory support (oxygen and mechanical ventilation) is provided as needed. Maintaining homeostasis involves correcting metabolic acidosis and electrolyte imbalances. Rewarming should be performed as needed, and hypoglycemia should be promptly corrected. Hepatoprotective agents (e.g., glucurolactone and glutathione) are commonly used to facilitate recovery from liver injury, and prophylactic B vitamins (B1, B12, and folate) are typically given to mitigate aplastic anemia risk (24). In the present case, gastric lavage, endotracheal intubation, CRRT, fluid resuscitation, acidosis correction, vasoactive agents, hepatoprotective therapy, cardioprotective measures, and stress ulcer prophylaxis aligned with management strategies documented in the existing literature and yielded favorable outcomes, including complete restoration of hepatic, renal, and cardiac function.