Part V: Guidelines for Known-pathogen Therapy

	Drug Choice		Alternatives		Remarks
Acinetobacter baumannii-calcoaceticus complex (ACBC)	•	I.V. ampicillin-sulbactam ± an aminoglycoside	•	Fluoroquinolone ± an aminoglycoside (if allergic to penicillin)	•	Sulbactam is highly active against ACBC.
Acinetobacter baumannii-calcoaceticus complex (ACBC)	•	I.V. ampicillin-sulbactam ± an aminoglycoside	•		•	For multidrug-resistant isolates: please consult a clinical microbiologist or infectious disease physician.
Clostridioides difficile	•	Initial non-severe episode: P.O. vancomycin or P.O. metronidazole (preferred for patients at low risk of recurrence) [133,529]	•	Severe disease, ileus or toxic megacolon: I.V. metronidazole + P.O. vancomycin ± per rectum vancomycin + consult surgeon	•	Multiple recurrences: please consult a clinical microbiologist or infectious disease physician regarding options, including vancomycin taper or faecal microbiota transplant. [530]
Clostridioides difficile	•	First recurrence, non-severe: P.O. vancomycin
Enterobacter cloacae complex	•	P.O. nitrofurantoin for uncomplicated/lower urinary tract infection	•	For severe infection, I.V. cefepime or I.V. carbapenem (for ESBL-producing strain)	•	Cefepime is highly active in vitro against almost all Enterobacter isolates.
	•	P.O./I.V. levofloxacin for complicated urinary tract infection			•	Emergence of AmpC derepressed mutants emerges in 20–40% of infections treated with the second- or third-generation cephalosporins. Use of these agents for serious infections is not recommended.
	•	I.V. piperacillin-tazobactam for non-severe infection			•	One study in Hong Kong found high prevalence of ESBL production among Enterobacter hormaechei (a member of the E. cloacae complex). [531]
					•	Resistance rate in 2023: nitrofurantoin (22%), levofloxacin (8%)
					•	For multidrug-resistant isolates: please consult a clinical microbiologist or infectious disease physician.
Escherichia coli (ESBL-negative)	•	(I.V./P.O. amoxicillin-clavulanate or I.V./P.O. cefuroxime) ± an aminoglycoside if rapid bactericidal action desirable on clinical grounds.	•	P.O./I.V. fluoroquinolones (if allergic to penicillin)
Haemophilus influenzae	•	P.O. amoxicillin or P.O./I.V. amoxicillin-clavulanate or I.V. ceftriaxone	•	P.O./I.V. fluoroquinolones (if allergic to penicillin)	•	Amoxicillin-clavulanate also provides good coverage for Moraxella catarrhalis and Streptococcus pneumoniae.
Klebsiella pneumoniae (ESBL-negative)	•	(I.V./P.O. amoxicillin-clavulanate or I.V./P.O. cefuroxime) ± an aminoglycoside if rapid bactericidal action desirable on clinical grounds.	•	P.O./I.V. fluoroquinolones (if allergic to penicillin)
Escherichia coli (ESBL-positive)	•	P.O. nitrofurantoin or P.O. amoxicillin-clavulanate for uncomplicated/lower urinary tract infection	•	I.V. carbapenem for bacteraemia or other severe infection	•	Carbapenem has been shown to be effective clinically and is currently the β-lactam agent of choice for serious infection by ESBL-positive Escherichia coli.
Escherichia coli (ESBL-positive)	•	I.V. piperacillin-tazobactam for non-severe infection
K. pneumoniae (ESBL-positive)	•	P.O. nitrofurantoin or P.O. amoxicillin-clavulanate for uncomplicated/lower urinary tract infection	•	I.V. carbapenem for bacteraemia or other severe infection	•	Carbapenem has been shown to be effective clinically and is currently the β-lactam agent of choice for serious infection by ESBL-positive Klebsiella pneumoniae.
K. pneumoniae (ESBL-positive)	•	I.V. piperacillin-tazobactam for non-severe infection	•	I.V. carbapenem for bacteraemia or other severe infection	•
Pseudomonas aeruginosa	•	(I.V. ceftazidime or I.V. cefepime or I.V. piperacillin-tazobactam) ± an aminoglycoside	•	I.V./P.O. levofloxacin/ciprofloxacin ± an aminoglycoside (if allergic to penicillin)	•	Meta-analysis demonstrated no difference in cure rate and mortality when treated with combination therapy. [532]
Pseudomonas aeruginosa	•				•	For multidrug-resistant isolates: please consult a clinical microbiologist or infectious disease physician.
Methicillin-sensitive Staphylococcus aureus (MSSA)	•	P.O./I.V. cloxacillin or I.V. cefazolin or P.O. cephalexin	•	I.V./P.O. amoxicillin-clavulanate
Methicillin-sensitive Staphylococcus aureus (MSSA)	•		•	Clindamycin (if allergic to penicillin)
Methicillin-resistant Staphylococcus aureus (MRSA)	•	I.V. vancomycin (bacteraemia or other invasive infections)	•	I.V. ceftaroline or I.V./P.O. linezolid or I.V. daptomycin if (1) vancomycin allergy - extensive rash, other than vancomycin infusion reaction (red man syndrome) develops after vancomycin, or (2) bacteraemia caused by MRSA with vancomycin MIC ≥2 microgram/mL.	•	Cotrimoxazole, fusidic acid or rifampicin are useful adjuncts for deep-seated infections (e.g. osteomyelitis) but these agents should not be administered as monotherapy.
					•	Considerations in the choice of agent include site of infection, individual patient’s circumstances such as underlying conditions and concurrent medications, risk of side effects and susceptibility profile.
					•	Most abscesses or uncomplicated skin and soft tissue infections caused by CA-MRSA could be treated with drainage and oral antibiotics with in vitro activities (e.g. clindamycin or cotrimoxazole).*
					•	Vancomycin intermediate Staphylococcus aureus/Vancomycin resistant Staphylococcus aureus: please consult a clinical microbiologist or infectious disease physician.
Mycoplasma pneumoniae	•	P.O./I.V. doxycycline	•	P.O./I.V. levofloxacin or moxifloxacin	•	Doxycycline is recommended in view of high incidence of macrolide-resistant Mycoplasma pneumoniae. [533]
Stenotrophomonas maltophilia	•	P.O./I.V. cotrimoxazole + I.V. ticarcillin-clavulanate	•	P.O./I.V. cotrimoxazole + P.O./I.V. (fluoroquinolone or minocycline)	•	Cotrimoxazole + ticarcillin-clavulanate is synergistic in vitro. Cotrimoxazole is a key component in therapy. [256,534]
Stenotrophomonas maltophilia					•	Combination therapy recommended for synergy and to prevent resistance.
Streptococcus pneumoniae (for infection outside the central nervous system)	•	Penicillin-sensitive (MIC ≤0.06 microgram/mL): I.V. penicillin G (4–8 million units/day, q6h)	•	β-lactam/β-lactamase inhibitor combination with the exception of cefoperazone-sulbactam (for mixed infections).	•	Most pneumococcal pneumonia can be treated with high dose amoxicillin or high dose amoxicillin-clavulanate.
	•	Penicillin-intermediate (MIC 0.12–1 microgram/mL): I.V. penicillin G (high dose, 12–18 million units/day, q4h)†	•	P.O./I.V. levofloxacin or P.O./I.V. moxifloxacin (if allergic to penicillin) for non-meningeal infections and penicillin-sensitive strains.	•	For pure pneumococcal infection, penicillin G instead of amoxicillin-clavulanate is preferred, switch therefore recommended.
	•	Penicillin-resistant (MIC ≥2 microgram/mL): I.V. ceftriaxone			•	>70% resistant to erythromycin. Cross-resistance to clindamycin very common.
					•	Resistance to erythromycin = resistance to other newer macrolides (clarithromycin, azithromycin).
Streptococcus pneumoniae (for central nervous system infection)	•	Penicillin-sensitive (MIC ≤0.06 microgram/mL): I.V. penicillin G (18–24 million units/day, q4h) or I.V. ampicillin 2 g q4h			•	MIC (meningitis) breakpoints for penicillin and ceftriaxone to be used here.
	•	Penicillin-resistant (MIC ≥0.12 microgram/mL) and third-generation cephalosporin MIC ≤0.5 microgram/mL: I.V. ceftriaxone 2 g q12h			•	In Streptococcus pneumoniae, cross resistance between penicillin and ceftriaxone/cefotaxime is common. [507,517] Local data indicates that approximately half of the penicillin-resistant (meningitis) isolates are intermediate/resistant (meningitis) to cefotaxime.
	•	Penicillin-resistant (MIC ≥0.12 microgram/mL) and third-generation cephalosporin MIC >0.5 microgram/mL: I.V. vancomycin plus I.V. ceftriaxone 2 g q12h			•
*For details, please refer to Figure 7.2. †These Clinical and Laboratory Standards Institute (CLSI) breakpoints were decided mainly for the relevance on meningitis. For pneumococcal pneumonia, pharmacokinetic/dynamic data indicates that isolates with penicillin MIC of up to 1–2 microgram/mL should be considered ‘sensitive’ to appropriate dose of penicillin, ampicillin and amoxicillin.