Part IV: Recommendation for the Empirical Therapy of Common Infections

4.1 Guidelines for empirical therapy

Musculoskeletal Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Septic arthritis, adult [334–338]	Staphylococcus aureus; Streptococcus agalactiae (Group B Streptococcus); Neisseria gonorrhoeae; other streptococci	I.V. cefazolin 2 g q8h or (I.V. cloxacillin + ampicillin)	I.V. ceftriaxone (if Neisseria gonorrhoeae or Gram-negative organism is suspected, ceftriaxone is the preferred choice.)	•	Urgent diagnostic tapping for Gram stain to guide therapy.
				•	Factors suggest N. gonorrhoeae aetiology: sexually active teenager/adult ± rash
				•	Consider Group B Streptococcus in patients with a history of handling raw freshwater fish. [339,340]
				•	Consider vancomycin in patients with risk factors for MRSA infection (e.g. known carriers, elderly home residents). [341]
Osteomyelitis, adult [342,343]				•	Occasionally Salmonella
				•	Often vertebral
				•	Intravenous drug user (IVDU): Staphylococcus aureus (vertebral); Pseudomonas aeruginosa (ribs, sternoclavicular joint).
				•	Consider vancomycin in patients with risk factors for MRSA infection (e.g. known carriers, elderly home residents). [341]
Vertebral	Staphylococcus aureus, streptococci, Escherichia coli	I.V. ceftriaxone
Non-vertebral	Staphylococcus aureus	I.V. cefazolin or I.V. cloxacillin
Diabetic foot infection [344–350]
Previously untreated, no osteomyelitis	Staphylococcus aureus, β-haemolytic streptococci	I.V./P.O. amoxicillin-clavulanate	I.V./P.O. clindamycin or P.O. cephalexin
Chronic, recurrent, limb threatening	Polymicrobial: aerobes + anaerobes	I.V./P.O. amoxicillin-clavulanate	If allergic to penicillins: I.V./P.O. levofloxacin/ ciprofloxacin + I.V./P.O. clindamycin For severe infections: piperacillin-tazobactam or meropenem	•	Cultures from ulcers unreliable.
				•	Early radical debridement to obtain tissue for culture; to exclude necrotising fasciitis and for cure.
				•	A positive probe-to-bone test involves using a sterile, blunt, stainless instrument to palpate bone in infected pedal ulcers, strongly correlating with underlying osteomyelitis. It is confirmed when a rock-hard, gritty structure is felt at the ulcer base without intervening soft tissue during gentle probing. [351,352]

Skin and Soft Tissue Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Erysipelas or cellulitis [353,354]	Streptococcus pyogenes, Streptococcus agalactiae, other streptococci, (± Staphylococcus aureus)	I.V./P.O. amoxicillin-clavulanate or I.V. cefazolin or P.O. cephalexin	If CA-MRSA concern: P.O. cotrimoxazole or P.O. linezolid or I.V. vancomycin (if severe infection).	•	In Hong Kong, 50%–80% Streptococcus pyogenes are resistant to clindamycin. [355,356]
Erysipelas or cellulitis [353,354]				•	Consider CA-MRSA coverage in cases of purulent cellulitis if risk factors present, non-responsive to first-line treatment and/or severe infection (systemic signs of infection, hypotension). [30]
Necrotising fasciitis [353,357,358]				•	Immediate radical surgical intervention essential. Urgent consult clinical microbiologist or infectious disease physician.
Following exposure to freshwater; seawater or seafood	Aeromonas hydrophila, Aeromonas caviae; Vibrio vulnificus	I.V. levofloxacin + I.V. amoxicillin-clavulanate		•	Aeromonas spp., including A. hydrophila and A. caviae possess the chromosomal carbapenemase, CphA which could cause resistance to meropenem and many other beta-lactams.
Following cuts and abrasion; recent chickenpox; IVDU; healthy adults; following intra-abdominal; gynaecological or perineal surgery [360]	Streptococcus pyogenes Polymicrobial: Enterobacterales, streptococci, anaerobes	I.V. meropenem + I.V./P.O. linezolid		•	Add high dose intravenous immunoglobulin (IVIG) (1 g/kg on day 1, followed by 0.5 g/kg on days 2 and 3) for streptococcal toxic shock syndrome. [359,361–363]
				•	In Hong Kong, 50%–80% Streptococcus pyogenes are resistant to clindamycin. [355,356]
				•	No clinical data exists on the benefit of clindamycin in clindamycin-resistant strains. In vitro and mice data are limited and contradictory. [364–367]
Infection bite wound (animal or human) [353,354,368,369]	Staphylococcus aureus, streptococci, anaerobes, Pasteurella multocida (cats and dogs), Capnocytophaga spp. (dogs), Eikenella spp. (human)	I.V./P.O. amoxicillin-clavulanate	(P.O. penicillin V or P.O. ampicillin) + P.O. cloxacillin Penicillin allergy: P.O. fluoroquinolones + P.O. clindamycin	•	Up to 18% of dog bites become infected; 28–80% of cat bites become infected. [370]
				•	Monotherapy with penicillin, cloxacillin or first-generation cephalosporin inadequate.
				•	Increasing prevalence of resistance in anaerobes; [371,372]
				•	Consider adding metronidazole empirically if poor response to cover anaerobes resistant to β-lactams or β-lactam/β-lactamase inhibitor combinations.
				•	Preemptive antimicrobial therapy for 3–5 days is recommended for patients who (a) are immunocompromised, (b) are asplenic, (c) have advanced liver disease, (d) have pre-existing or resultant edema of the affected area, (e) have moderate to severe injuries, especially to the hand or face, or (f) have injuries that may have penetrated the periosteum or joint capsule. [353]

Central Nervous System Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Brain abscess [373–375]	Usually polymicrobial with aerobes and anaerobes	I.V. ceftriaxone + I.V. metronidazole	I.V. meropenem	•	Urgent consult neurosurgery.
				•	Exclude primary focus in middle ear, mastoid, paranasal sinuses, dental and lung.
				•	Carbapenem use is associated with a small increased risk of seizures compared with non-carbapenem group of antibiotics. [376]
Meningitis [377–381]	Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus suis, Haemophilus influenzae	I.V. ceftriaxone + I.V. vancomycin [382]	I.V. meropenem + I.V. vancomycin	•	If impaired cellular immunity (e.g. high dose steroid) consider adding ampicillin to cover Listeria spp. [383]
				•	Promptly review rapid test result (e.g. Gram stain, polymerase chain reaction) and streamline antibiotics accordingly. [384]
				•	An adjuvant regimen of dexamethasone at 0.15 mg/kg I.V. q6h for 4 days is recommended to be administered either 15–20 min before the first dose of antibiotics or simultaneously with the first dose of antibiotics. [384,385]
				•	In adults, adjunctive steroids have demonstrated a reduction in mortality and/or hearing loss specifically in cases of meningitis caused by Streptococcus pneumoniae or Streptococcus suis. The efficacy of steroids in meningitis caused by other bacteria and whether a 2-day course is as effective as a 4-day course, remains uncertain. [385–388]

Intra-abdominal and Gastrointestinal System Infections (Community-Acquired)

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Secondary peritonitis (perforated peptic ulcer, other bowel perforation, ruptured appendicitis, diverticulitis) [389–392]	Enterobacterales, Bacteroides fragilis group, other anaerobes, enterococci	I.V. amoxicillin-clavulanate or I.V. piperacillin-tazobactam	I.V. cefuroxime + I.V. metronidazole Severe infections (e.g. due to ruptured colon): I.V. meropenem + metronidazole	•	Surgical intervention essential.
				•	β-lactam/β-lactamase inhibitor combinations or meropenem usually can provide coverage against anaerobes. However, due to increasing prevalence of resistance in anaerobes to β-lactams and β-lactam/β-lactamase inhibitor combinations, consider adding metronidazole empirically in patients with severe infections or suboptimal response. [371,372,393]
Cholangitis, cholecystitis or other biliary sepsis [392,394]	Enterobacterales, enterococci, Bacteroides fragilis group	I.V. amoxicillin-clavulanate or I.V. piperacillin-tazobactam	I.V. cefuroxime + I.V. metronidazole Severe infections: I.V. meropenem + metronidazole	•	Adequate biliary drainage essential.
				•	Send bile for culture.
				•	β-lactam/β-lactamase inhibitor combinations cover most Enterobacterales, enterococci and anaerobes.
Liver abscess (community-acquired) [394–396]	Klebsiella pneumoniae and other Enterobacterales, Bacteroides fragilis group, enterococci, Entamoeba histolytica, Streptococcus anginosus group	I.V. ceftriaxone + I.V./P.O. metronidazole (for Entamoeba histolytica)	I.V. amoxicillin-clavulanate + I.V./P.O. metronidazole (for Entamoeba histolytica) Severe infections: I.V. meropenem + I.V./P.O. metronidazole (for Entamoeba histolytica)	•	The detection of Entamoeba histolytica by PCR in liver pus/stool, and serological assay are valuable for diagnosing amoebic liver abscess. [397]
				•	Image-guided or open drainage for large abscess.
				•	For amoebic infection: high dose metronidazole for 10 days then followed by diloxanide. [398,399]
				•	Ophthalmological assessment to rule out endophthalmitis if pus aspirate grew Klebsiella pneumoniae. Endogenous endophthalmitis in patients with Klebsiella liver abscess occurred in 3% to 10.4%, especially if diabetes mellitus. [400–407]
				•	Ceftriaxone (meningitic dose) is the drug of choice for better central nervous system penetration if concomitant central nervous system involvement is likely to occur. Use of amoxicillin-clavulanate should be reserved for patients with drained abscess, clinical responding and without evidence of endophthalmitis.
Mild gastroenteritis	Mostly viral in origin; Food poisoning (Bacillus cereus, Staphylococcus aureus, Clostridium perfringens), Salmonella, Escherichia coli, Campylobacter spp., Aeromonas spp.	Routine antibiotic therapy not recommended.		•	Fluid and electrolytes replacement.
Moderate to severe gastroenteritis (presume bacterial) in persons with immunosuppressive disease [e.g. for human immunodeficiency virus (HIV) +ve; high dose steroid when laboratory results not available] [408–413]	Campylobacter spp., Salmonella, Shigella spp., Vibrio spp.	P.O. azithromycin	P.O. ciprofloxacin	•	Fluoroquinolone resistance is very high in Campylobacter and is also on the rise in Salmonella. [414–416]
				•	Consider Clostridioides difficile infection in patients recently treated with antibiotics (please refer to known-pathogen therapy Part V for Clostridioides difficile infection treatment).
				•	Replace fluid and electrolytes;
				•	Avoid antimotility agents, e.g. loperamide [Imodium], diphenoxylate/atropine [Lomotil]. [417,418]
Traveller’s diarrhoea (Incidence 10–40% usually self-limiting) [408,413,419–423]	Enterotoxigenic Escherichia coli (ETEC) and Enteroaggregative Escherichia coli (EAEC), Shigella spp., Salmonella, Campylobacter spp., rarely Aeromonas spp., Plesiomonas	P.O. azithromycin	P.O. rifaximin (for non-invasive infections)	•	Avoid antimotility agents, e.g. loperamide [Imodium], diphenoxylate/atropine [Lomotil], especially if fever or blood in stool.
		P.O. azithromycin	P.O. rifaximin (for non-invasive infections)	•	Patients from South Asia: concern of Salmonella with resistance to ceftriaxone and fluoroquinolones. [424,425]

Cardiovascular Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Subacute infective endocarditis (chronic rheumatic heart disease, degenerative or congenital valvular diseases) [426–432]	S. viridans, S. gallolyticus group, Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, Kingella spp. (HACEK), Enterococci	I.V. ceftriaxone ± I.V. ampicillin		•	The choice of empirical therapy should take into account the most likely pathogens. Obtain at least 3 sets of blood cultures, ideally by 3 different venepunctures and spaced over 30–60 minutes (put down ‘suspected infective endocarditis’ in test request); then start I.V. antibiotics as soon as possible. [433,434]
Acute infective endocarditis (intravenous drug users) [426–432]	S. aureus	I.V. cloxacillin 2 g q4h	I.V. cefazolin 2 g q8h	•	Usually tricuspid valve infection ± metastatic lung abscesses.
				•	Blood culture for 3 sets (label ‘suspected infective endocarditis’ in test request); then start I.V. antibiotics immediately. [433,434]
				•	MRSA concern: Local prevalence of CA-MRSA is low and invasive infection is still rare. [28,435]
				•	Consider adding empirical vancomycin if there are risk factors for MRSA infection, or if the patient is critically ill.
				•	Consider adding empirical coverage for Gram-negative and fungal organisms, such as Pseudomonas aeruginosa and Candida spp. in critically ill patients. [436]

Gynaecological Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Pelvic inflammatory disease (PID) (or upper genital tract infection) [437–440]	Neisseria gonorrhoeae, Chlamydia trachomatis, Enterobacterales, anaerobes	Inpatient: I.V. ceftriaxone 2 g q24h + P.O. doxycycline ± P.O. metronidazole or (I.V. amoxicillin-clavulanate + P.O. doxycycline)	Inpatient: I.V. clindamycin 600–900 mg q8h + I.V. gentamicin 3 mg/kg q24h × 1 to 2 doses; once stabilised, switch to oral clindamycin plus doxycycline for completion of therapy.	•	Gentamicin is an alternative to ceftriaxone in gonococcal infections. [441,442] and can be considered in patients with severe β-lactam allergy.
				•	Coverage of anaerobes important in tubo-ovarian abscess, co-existing bacterial vaginosis, HIV positive. [443]
				•	The following regimen can be considered for outpatient therapy of mild-to-moderately severe acute PID: I.M. ceftriaxone 500 mg single dose + P.O. doxycycline ± P.O. metronidazole. [439]
				•	Due to high prevalence of gonococcal resistance, P.O ceftibuten or fluoroquinolones not suitable for empirical treatment of acute PID. [443–445]
Breast abscess [446–448]	Staphylococcus aureus (± anaerobes in non-puerperal abscess)	I.V./P.O. amoxicillin-clavulanate	(I.V. cefazolin or P.O. cephalexin 1 g q.i.d.) (+P.O. metronidazole if anaerobes likely)	•	Incision and drainage essential; send pus for Gram smear and culture.

Head and Neck Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Odontogenic or neck infection [449–451]	Oral anaerobes	I.V./P.O. amoxicillin-clavulanate	(P.O. amoxicillin + P.O. metronidazole) or I.V./P.O. clindamycin

Urinary Tract Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Cystitis [234,452–454]	Escherichia coli; Staphylococcus saprophyticus, Streptococcus agalactiae	P.O. nitrofurantoin or P.O. amoxicillin-clavulanate		•	Encourage fluid intake.
Cystitis [234,452–454]		P.O. nitrofurantoin or P.O. amoxicillin-clavulanate		•	Nitrofurantoin should be used with caution in elderly patients; avoid in patients with creatinine clearance <30 mL/min. [455]
Acute pyelonephritis [234,452–454,456,457]	Enterobacterales, Enterococcus, (Pseudomonas in catheter-related, obstructive uropathy or transplant)	I.V. amoxicillin-clavulanate	(I.V. piperacillin-tazobactam if P. aeruginosa suspected) or (I.V. imipenem or I.V. meropenem if ESBL-producing organisms suspected)	•	Blood culture and midstream urine (MSU) cultures, need to rule out obstructive uropathy.
				•	I.V. until afebrile 24–48 h, then switch to oral drugs based on susceptibility for completion of therapy.
				•	Carbapenem is recommended for severe or rapidly-deteriorating cases.

Respiratory Tract Infections

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
Acute bacterial exacerbation of chronic bronchitis (ABECB) - Appropriate use of antibiotics in ABECB is imperative to help control the emergence of multidrug resistant organisms. [458–462]	Respiratory viruses, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis	I.V./P.O. amoxicillin-clavulanate [total antibiotic duration of 5–7 days] [463,464]	I.V. ceftriaxone [I.V./P.O. fluoroquinolone may be considered for penicillin allergy, or suspected Pseudomonas aeruginosa infection] [total antibiotic duration of 5–7 days] [463,464]	•	Antibiotics should be given to patients with:
					a) Following three cardinal symptoms: increased dyspnoea, increased sputum volume, increased sputum purulence;
					b) Increased sputum purulence and one other cardinal symptom;
					c) Requiring mechanical ventilation (invasive or non-invasive)
				•	Streptococcus pneumoniae (MIC 1–2 microgram/mL) can be treated by high dose P.O. amoxicillin e.g. at least 1.5 g/day or I.V. penicillin G (high dose amoxicillin-clavulanate e.g. 1 g b.i.d. if co-infection by ampicillin-resistant H. influenzae). [459]
Acute bacterial exacerbation or pneumonia in patients with bronchiectasis [465–468]	Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae	I.V. piperacillin-tazobactam	I.V. ceftazidime [Anti-pseudomonal fluoroquinolones may be used for treatment of susceptible Pseudomonas aeruginosa]	•	For Pseudomonas aeruginosa, ciprofloxacin or levofloxacin should be given at high dose (e.g. P.O. 500 mg b.i.d. or 500–750 mg daily respectively).
Aspiration pneumonia [469,470]	Oral anaerobes: Bacteroides, Peptostreptococci, Fusobacterium, Streptococcus milleri group	I.V./P.O. amoxicillin-clavulanate	(I.V. ceftriaxone + P.O. metronidazole), I.V. ticarcillin-clavulanate or I.V. piperacillin-tazobactam	•	Penicillin allergy: levofloxacin plus (clindamycin or metronidazole)

Community-Acquired Pneumonia (CAP)

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
CAP, not hospitalised [471,472]	Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci (influenza A, M. tuberculosis)	P.O. amoxicillin-clavulanate (e.g. 1 g b.i.d.) ± doxycycline or P.O. high dose amoxicillin (at least 1.5 g/day) ± doxycycline	P.O. levofloxacin	•	Penicillin allergy: levofloxacin
CAP, hospitalised in general ward [471–476]	As above	I.V./P.O. amoxicillin-clavulanate ± P.O. doxycycline	I.V. ceftriaxone ± P.O. doxycycline	•	Modifying factors: bronchiectasis: either (ticarcillin-clavulanate or piperacillin-tazobactam or cefepime) + a macrolide; or fluoroquinolone + an aminoglycoside
				•	Low prevalence of Mycoplasma pneumoniae infections in patients aged above 65.
				•	If empirical coverage of atypical pneumonia is necessary for patients aged above 65, consider replacing doxycycline with macrolides or quinolones.
				•	Local prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) is estimated to be >40%, hence doxycycline is the preferred atypical coverage for younger hospitalised patients in general wards. [113]
				•	With concern for influenza: add oseltamivir 75 mg b.i.d.
CAP, hospitalised in ICU or serious pneumonia [471–477]	As above + Legionella pneumophila + Enterobacterales	I.V. piperacillin-tazobactam or ceftriaxone + a macrolide [doxycycline is preferred over macrolides for young patients at low risk of Legionella pneumonia, to cover macrolide-resistant Mycoplasma pneumoniae (MRMP).] [+P.O. oseltamivir 75 mg b.i.d. during influenza season]	I.V. cefepime + a macrolide (or P.O. doxycycline)	•	Ticarcillin-clavulanate and ceftazidime are not useful against penicillin-non-susceptible Streptococcus pneumoniae.
CAP, hospitalised in ICU or serious pneumonia [471–477]	As above + Legionella pneumophila + Enterobacterales		I.V. cefepime + a macrolide (or P.O. doxycycline)	•	With concern for CA-MRSA: (e.g. presence of Gram-positive cocci in cluster, history of recurrent boils/abscesses or skin infections or preceding ‘flu-like’ illness, severe disease), add I.V. linezolid 600 mg q12h (preferred) or I.V. vancomycin 1 g q12h.

Hospital-Acquired Pneumonia (HAP)

	Usual organisms	Preferred regimens	Alternatives	Special considerations/Remarks
HAP, onset <4 days after admission + no previous antibiotics [478–481]	Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus	I.V./P.O. amoxicillin-clavulanate	I.V. ceftriaxone
HAP, onset ≥4 days after admission + had antibiotics recently, OR onset ≥5 days after admission OR mechanical ventilation [478–481]	MRSA, Pseudomonas aeruginosa, Acinetobacter, Klebsiella spp., Enterobacter spp.	I.V. piperacillin-tazobactam	I.V. cefepime or I.V. ceftazidime	•	With ESBL-E concern: I.V. imipenem-cilastatin/meropenem
		I.V. piperacillin-tazobactam	I.V. cefepime or I.V. ceftazidime	•	With MRSA concern: Add I.V. vancomycin