Table 2. Role of antibiotics in... | American Society of Hematology

Table 2.

Role of antibiotics in modulating microbiota and outcomes of cellular therapy

Antibiotics	Targets	Microbial effects	Impact on cellular therapy
Auto-HCT
Piperacillin-tazobactam	Cell wall synthesis	↓ α-Diversity⁶⁵	↓ Neutropenic fever⁶¹
Vancomycin (IV)	Cell wall synthesis	↓ α-Diversity⁶⁵ Change in β-diversity⁶⁵	↓ Neutropenic fever⁶² ↓ Bacteremia⁶²
Doxycycline	Protein synthesis (30S)	Change in β-diversity⁶⁵	↓ Central venous catheter infections⁶⁶
Ciprofloxacin	Nucleic acid synthesis	↓ Aerobes	↓ Neutropenic fever⁶² ↓ Bacteremia⁶²
Allo-HCT
Any antibiotics	—	↓ Clostridia⁵⁰	↑ Transplant-related mortality⁵⁰^, ↑ aGVHD⁴⁷ ↓ OS⁴⁷
Combination of antimicrobial medications	—	Total gastrointestinal decontamination	↓ aGVHD⁵⁶ ↓ Bacteremia⁶⁴
Anaerobic antibiotics	—	↓ Anaerobes ↓ α-Diversity⁴⁸	↑ Lower respiratory tract disease⁵² ↑ Respiratory viral infections⁵²
Penicillins with or without a β-lactamase inhibitor	Cell wall synthesis	↓ Gram-positive bacteria	↑ aGVHD⁵⁷
Piperacillin-tazobactam	Cell wall synthesis	↓ Bacteroidetes⁴⁹^, ↓ Lactobacillus⁴⁹^, ↓ Bifidobacteriales⁴⁸^, ↓ Clostridiales⁴⁸ ↓ Anaerobes¹⁵	↑ GVHD⁴⁹ ↑ GVHD-related mortality⁴⁸
Third-generation or higher cephalosporins	Cell wall synthesis	Change in β-diversity⁶⁵	↑ aGVHD⁵⁷
Aztreonam	Cell wall synthesis	↓ Gram-negative aerobes	↑ aGVHD⁵⁷
Carbapenems	Cell wall synthesis	↑ Bacteroides⁵⁹^, ↓ Enterococcus and UBA1819⁵⁹^, ↓ Anaerobes¹⁵^, Change in β-diversity⁶⁵^, ↓ Bifidobacteriales⁴⁸ ↓ Clostridiales⁴⁸	↑ aGVHD⁵⁷^,⁵⁸ ↑ Intestinal aGVHD⁵⁹ ↑ GVHD-related mortality⁴⁸^,⁴⁹ ↓ Fever episodes⁶⁷
Vancomycin (IV)	Cell wall synthesis	↓ α-Diversity⁶⁵ Change in β-diversity⁶⁵	↑ aGVHD⁵⁷ ↑ CMV reactivation⁵³
Doxycycline	Protein synthesis (30S)	Change in β-diversity⁶⁵	↓ Central venous catheter infections⁶⁶
Azithromycin	Protein synthesis (50S)	↓ Aerobes and anaerobes	↑ Overall mortality²⁷^, ↑ T-cell exhaustion⁵¹^, ↑ Relapse⁵¹ ↑ Viral lower respiratory tract infection⁵⁴
Clindamycin	Protein synthesis (50S)	↓ Gut anti-inflammatory Clostridia⁶⁰	↑ GVHD⁶⁰
Fluoroquinolones	Nucleic acid synthesis	↑ Proteobacteria domination¹⁴	↑ aGVHD⁵⁷^, ↑ Bacteremia with aerobic gram-negative bacilli¹⁴^, ↑ Pulmonary complications²⁷ ↑ Overall mortality²⁷
Metronidazole	Nucleic acid synthesis	↑ Enterococcal domination¹⁴ Change in β-diversity⁶⁵ ↓ Butyrate-producing bacteria	↑ Vancomycin-resistant Enterococcus bacteremia¹⁴^, ↑ Overall mortality²⁷ ↓ aGVHD⁶³
Trimethoprim-sulfamethoxazole	Metabolic pathway (antifolate)	Change in β-diversity⁶⁵ ↑ Fluoroquinolone-resistant Enterobacterales colonization⁵⁵	↑ aGVHD⁵⁷ ↑ Gram-negative bloodstream infections⁵⁵
CAR T-cell therapy
Any antibiotics	—	—	↓ OS⁶⁸^,⁶⁹ ↑ Progression⁶⁹
PIM	Cell wall synthesis	↓ Anaerobes	↓ OS⁶⁸^, ↓ PFS⁶⁸ ↑ ICANS⁶⁸
High-risk antibiotics (meropenem, cefepime, ceftazidime and piperacillin-tazobactam)	Cell wall synthesis	↓ α-Diversity⁶⁹^, Change in β-diversity⁶⁹^, ↓ Roseburia, Bifidobacterium, Lactobacillus, and Eubacterium spp⁶⁹ ↑ Prevotella, Veillonella or Enterococcus spp⁶⁹	↓ OS⁶⁹^, ↓ PFS⁶⁹^, ↑ Tumor burden⁶⁹^, ↑ Serum LDH and CRP⁶⁹^, ↓ Peripheral T-cell counts⁶⁹ ↑ ICANS⁶⁹

Antibiotics	Targets	Microbial effects	Impact on cellular therapy
Auto-HCT
Piperacillin-tazobactam	Cell wall synthesis	↓ α-Diversity⁶⁵	↓ Neutropenic fever⁶¹
Vancomycin (IV)	Cell wall synthesis	↓ α-Diversity⁶⁵ Change in β-diversity⁶⁵	↓ Neutropenic fever⁶² ↓ Bacteremia⁶²
Doxycycline	Protein synthesis (30S)	Change in β-diversity⁶⁵	↓ Central venous catheter infections⁶⁶
Ciprofloxacin	Nucleic acid synthesis	↓ Aerobes	↓ Neutropenic fever⁶² ↓ Bacteremia⁶²
Allo-HCT
Any antibiotics	—	↓ Clostridia⁵⁰	↑ Transplant-related mortality⁵⁰^, ↑ aGVHD⁴⁷ ↓ OS⁴⁷
Combination of antimicrobial medications	—	Total gastrointestinal decontamination	↓ aGVHD⁵⁶ ↓ Bacteremia⁶⁴
Anaerobic antibiotics	—	↓ Anaerobes ↓ α-Diversity⁴⁸	↑ Lower respiratory tract disease⁵² ↑ Respiratory viral infections⁵²
Penicillins with or without a β-lactamase inhibitor	Cell wall synthesis	↓ Gram-positive bacteria	↑ aGVHD⁵⁷
Piperacillin-tazobactam	Cell wall synthesis	↓ Bacteroidetes⁴⁹^, ↓ Lactobacillus⁴⁹^, ↓ Bifidobacteriales⁴⁸^, ↓ Clostridiales⁴⁸ ↓ Anaerobes¹⁵	↑ GVHD⁴⁹ ↑ GVHD-related mortality⁴⁸
Third-generation or higher cephalosporins	Cell wall synthesis	Change in β-diversity⁶⁵	↑ aGVHD⁵⁷
Aztreonam	Cell wall synthesis	↓ Gram-negative aerobes	↑ aGVHD⁵⁷
Carbapenems	Cell wall synthesis	↑ Bacteroides⁵⁹^, ↓ Enterococcus and UBA1819⁵⁹^, ↓ Anaerobes¹⁵^, Change in β-diversity⁶⁵^, ↓ Bifidobacteriales⁴⁸ ↓ Clostridiales⁴⁸	↑ aGVHD⁵⁷^,⁵⁸ ↑ Intestinal aGVHD⁵⁹ ↑ GVHD-related mortality⁴⁸^,⁴⁹ ↓ Fever episodes⁶⁷
Vancomycin (IV)	Cell wall synthesis	↓ α-Diversity⁶⁵ Change in β-diversity⁶⁵	↑ aGVHD⁵⁷ ↑ CMV reactivation⁵³
Doxycycline	Protein synthesis (30S)	Change in β-diversity⁶⁵	↓ Central venous catheter infections⁶⁶
Azithromycin	Protein synthesis (50S)	↓ Aerobes and anaerobes	↑ Overall mortality²⁷^, ↑ T-cell exhaustion⁵¹^, ↑ Relapse⁵¹ ↑ Viral lower respiratory tract infection⁵⁴
Clindamycin	Protein synthesis (50S)	↓ Gut anti-inflammatory Clostridia⁶⁰	↑ GVHD⁶⁰
Fluoroquinolones	Nucleic acid synthesis	↑ Proteobacteria domination¹⁴	↑ aGVHD⁵⁷^, ↑ Bacteremia with aerobic gram-negative bacilli¹⁴^, ↑ Pulmonary complications²⁷ ↑ Overall mortality²⁷
Metronidazole	Nucleic acid synthesis	↑ Enterococcal domination¹⁴ Change in β-diversity⁶⁵ ↓ Butyrate-producing bacteria	↑ Vancomycin-resistant Enterococcus bacteremia¹⁴^, ↑ Overall mortality²⁷ ↓ aGVHD⁶³
Trimethoprim-sulfamethoxazole	Metabolic pathway (antifolate)	Change in β-diversity⁶⁵ ↑ Fluoroquinolone-resistant Enterobacterales colonization⁵⁵	↑ aGVHD⁵⁷ ↑ Gram-negative bloodstream infections⁵⁵
CAR T-cell therapy
Any antibiotics	—	—	↓ OS⁶⁸^,⁶⁹ ↑ Progression⁶⁹
PIM	Cell wall synthesis	↓ Anaerobes	↓ OS⁶⁸^, ↓ PFS⁶⁸ ↑ ICANS⁶⁸
High-risk antibiotics (meropenem, cefepime, ceftazidime and piperacillin-tazobactam)	Cell wall synthesis	↓ α-Diversity⁶⁹^, Change in β-diversity⁶⁹^, ↓ Roseburia, Bifidobacterium, Lactobacillus, and Eubacterium spp⁶⁹ ↑ Prevotella, Veillonella or Enterococcus spp⁶⁹	↓ OS⁶⁹^, ↓ PFS⁶⁹^, ↑ Tumor burden⁶⁹^, ↑ Serum LDH and CRP⁶⁹^, ↓ Peripheral T-cell counts⁶⁹ ↑ ICANS⁶⁹

The symbol ↑ represents an increase, and the symbol ↓ represents a decrease.

CMV, cytomegalovirus; CRP, C-reactive protein; LDH, lactate dehydrogenase; PIM, piperacillin/tazobactam, imipenem/cilastatin, and meropenem.

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