Ceftazidime

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications 

• Severe infections including septicaemia, bacteraemia, peritonitis and in immunocompromised patients caused by Streptococcus pyogenes, Streptococcus Group B, Streptococcus pneumoniae, Streptococcus mitis, Streptococcus spp. Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Salmonella spp., Acinetobacter spp., Yersinia enterocolitica or Pasteurella multocida 
• Respiratory tract Infections, such as pneumonia, bronchopneumonia and bronchitis (including lung infections in patients with cystic fibrosis) caused by Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Haemophilus parainfluenzae, Escherichia coli, Streptococcus pyogenes, Proteus mirabilis, Serratia spp. and Enterobacter spp.
• Ear, nose and throat infections caused by Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Haemophilus parainfluenzae, Escherichia coli, Streptococcus pyogenes, Proteus mirabilis, Serratia spp. and Enterobacter spp.
• Urinary tract infections caused by Neisseria gonorrhoeae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii, Enterobacter spp, Citrobacter spp.
• Skin and soft tissue infections caused by Streptococcus pyogenes, Streptococcus spp., Escherichia coli, Enterobacter spp, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii
• Gastrointestinal, biliary and abdominal infections caused by Escherichia coli, Klebsiella pneumoniae, Streptococcus spp., Salmonella spp., Shigella spp., Yersinia enterocolitica

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to any other cephalosporin
• History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems

Cautions

• Pregnancy
• Renal impairment 
• Severe hepatic impairment
• Elderly
• Porphyria
• History of non-severe hypersensitivity to other beta-lactam agents
• Monotherapy in some types of infections, such as bacteraemia, bacterial meningitis, skin and soft tissue infections, and bone and joint infections (unless the pathogen is already documented and known to be susceptible to treatment with ceftazidime)
• Prevalence of extended-spectrum beta-lactamase-producing organisms
• Prolonged use
• Coadministration of high dose cephalosporins with nephrotoxic medicinal products such as aminoglycosides or potent diuretics (e.g. furosemide)
• Sodium-controlled diet
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• General dosing range
• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages 
• Indications and dosages registered in other jurisdictions

Infections caused by: Some Gram-positive aerobes, such as Streptococcus pyogenes, Streptococcus agalactiae; Some Gram-negative aerobes, such as Citrobacter koseri, Haemophilus influenzae, Moraxella catarrhalis, Pasteurella multocida, Neisseria meningitidis, Proteus mirabilis, Proteus spp (other), Providencia spp. 

General dosing range 

• IM/IV: 1-2g, 8-12hrly

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Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Bacterial endophthalmitis (Additional agent required)
- Endogenous endophthalmitis
- Post-surgical endophthalmitis 

• Intravitreal: 2.25mg, as a single dose
  (STG, Adult 2019)

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South African registered indications and dosages

Urinary tract infections
- Caused by Neisseria gonorrhoeae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Proteus vulgaris, Morganella morganii, Enterobacter spp., or Citrobacter spp.
Less severe infections

• IV/IM: 500mg-1000mg, 12hrly

Respiratory tract Infections, such as pneumonia, bronchopneumonia and bronchitis 
- Caused by Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Haemophilus parainfluenzae, Escherichia coli, Streptococcus pyogenes, Proteus mirabilis, Serratia spp. and Enterobacter spp.
Ear, nose and throat infections 
- Caused by Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Haemophilus parainfluenzae, Escherichia coli, Streptococcus pyogenes, Proteus mirabilis, Serratia spp. and Enterobacter spp.
Skin and soft tissue infections 
- Caused by Streptococcus pyogenes, Streptococcus spp., Escherichia coli, Enterobacter spp, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii
Gastrointestinal, biliary and abdominal infections  
- Caused by Escherichia coli, Klebsiella pneumoniae, Streptococcus spp., Salmonella spp., Shigella spp., Yersinia enterocolitica

• IV/IM: 1g, 8hrly
  OR
• IV/IM: 2g, 12hrly 

Severe infections, including septicaemia, bacteraemia, peritonitis 
- Caused by Streptococcus pyogenes, Streptococcus Group B, Streptococcus pneumoniae, Streptococcus mitis, Streptococcus spp. Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Salmonella spp., Acinetobacter spp., Yersinia enterocolitica or Pasteurella multocida 
Infections in immunocompromised patients, including those with neutropenia

• IVIM: 2g, 8-12hrly

Cystic fibrosis 
- Fibrocystic patients who have pseudomonal lung infections (with normal renal function)

• IV/IM: 100-150mg/kg/day, in 3 divided doses

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In adults with normal renal function, 9g/24hrs has been used

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May be given IV or by deep IM injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh

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Ceftazidime dosage depends upon the severity, sensitivity and type of infection and the age, mass and renal function of the patient

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Indications and dosages registered in other jurisdictions

Febrile neutropenia
Nosocomial pneumonia
Bacterial meningitis
Bacteraemia (where associated with, or suspected to be associated with, any of the infections)

- Intermittent administration

• IV: 2g, 8hrly

- Continuous infusion

• IV: Loading dose: 2g; THEN 4-6g/24hrs as a continuous infusion

Bronchopulmonary infections in cystic fibrosis

- Intermittent administration

• IV: 100-150mg/kg/day, 8hrly; Max: 9g/24hrs 

- Continuous infusion

• IV: Loading dose: 2g; THEN 4-6g/24hrs as a continuous infusion

Bone and joint infections
Complicated skin and soft tissue infections
Complicated intra-abdominal infections
Peritonitis associated with dialysis in patients on continuous ambulatory peritoneal dialysis

- Intermittent administration

• IV: 1-2g, 8hrly

- Continuous infusion

• IV: Loading dose: 2g; THEN 4-6g/24hrs as a continuous infusion

Chronic suppurative otitis media
Malignant otitis externa

- Intermittent administration

• IV: 1-2g, 8hrly

Complicated urinary tract infections

- Intermittent administration

• IV: 1-2g, 8-12hrly

Per-operative prophylaxis for transurethral resection of prostate (TURP)

• IV: 1g, at induction of anaesthesia; THEN: 1g, at catheter removal

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The dose depends on the severity, susceptibility, site and type of infection and on the age and renal function of the patient. The selection of ceftazidime should take into account its antibacterial spectrum, which is mainly restricted to aerobic Gram-negative bacteria

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Ceftazidime should be co-administered with other antibacterial agents whenever the possible range of causative bacteria would not fall within its spectrum of activity

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Ceftazidime should be administered by IV injection or infusion. Solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids

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The standard recommended route of administration is by IV intermittent injection or IV continuous infusion

Paed. form avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• General dosing range
• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages 
• Indications and dosages registered in other jurisdictions

Infections caused by: Some Gram-positive aerobes, such as Streptococcus pyogenes, Streptococcus agalactiae; Some Gram-negative aerobes, such as Citrobacter koseri, Haemophilus influenzae, Moraxella catarrhalis, Pasteurella multocida, Neisseria meningitidis, Proteus mirabilis, Proteus spp (other), Providencia spp. 

General dosing range 

Younger than 28 days

• No information available

Older than 28 days

• IV: 150-300mg/kg/day, in 3 divided doses, 8hrly

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Acute osteitis/osteomyelitis (Additional agent required)
- Penetrating foot bone injuries

• IV: 50mg/kg, 6hrly, can transition to oral therapy once there is sustained clinical improvement, resolution of fever and CRP<30mg/L 
  (STG, Paed. 2017)

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South African registered indications and dosages

Respiratory tract Infections, such as pneumonia, bronchopneumonia and bronchitis 
- Caused by Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Haemophilus parainfluenzae, Escherichia coli, Streptococcus pyogenes, Proteus mirabilis, Serratia spp. and Enterobacter spp.
Ear, nose and throat infections 
- Caused by Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Haemophilus parainfluenzae, Escherichia coli, Streptococcus pyogenes, Proteus mirabilis, Serratia spp. and Enterobacter spp.
Urinary tract infections 
- Caused by Neisseria gonorrhoeae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii, Enterobacter spp, Citrobacter spp.
Skin and soft tissue infections 
- Caused by Streptococcus pyogenes, Streptococcus spp., Escherichia coli, Enterobacter spp, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii
Gastrointestinal, biliary and abdominal infections  
- Caused by Escherichia coli, Klebsiella pneumoniae, Streptococcus spp., Salmonella spp., Shigella spp., Yersinia enterocolitica

Neonates and children <2 months  

• IV: 60mg/kg/day, in 2 divided doses

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Clinical experience is limited in this age group

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Older than 2 months

• IV: 30-100mg/kg/day, in 2-3 divided doses

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The dosage for children older than 2 months but younger than 1 year is generally 25-50mg/kg, 12hrly

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Cystic fibrosis
Infections in immunocompromised children

Neonates and children younger than 2 months  

• No information available

Older than 2 months

• IV: Max: 50mg/kg, 8hrly; Max: 6g/24hrs

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Ceftazidime is to be used by the parenteral route and the dosage depends upon the severity, sensitivity and type of infection and the age, mass and renal function of the patient

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Indications and dosages registered in other jurisdictions

Neonates and infants ≤2 months

Most infections

 - Intermittent administration

• IV: 25-60mg/kg/day, in 2 divided doses

- Continuous infusion

• Not established for use

Older than 2 months and <40kg

Bacterial meningitis
Bacteraemia (where associated with, or suspected to be associated with, any of the infections)

- Intermittent administration

• IV: 150mg/kg/day, in 3 divided doses; Max: 6g/24hrs 

- Continuous infusion

• IV: Loading dose: 60-100mg/kg; THEN 100-200mg/kg/day as a continuous infusion; Max: 6g/24hrs 

Bone and joint infections
Complicated skin and soft tissue infections
Complicated intra-abdominal infections
Peritonitis associated with dialysis in patients on continuous ambulatory peritoneal dialysis

- Intermittent administration

• IV: 100-150mg/kg/day, in 3 divided doses; Max: 6g/24hrs 

- Continuous infusion

• IV: Loading dose: 60-100mg/kg; THEN 100-200mg/kg/day as a continuous infusion; Max: 6g/24hrs 

Bronchopulmonary infections in cystic fibrosis

- Intermittent administration

• IV: 150mg/kg/day, in 3 divided doses; Max: 6g/24hrs 

- Continuous infusion

• IV: Loading dose: 60-100mg/kg; THEN 100-200mg/kg/day as a continuous infusion; Max: 6g/24hrs 

Chronic suppurative otitis media
Malignant otitis externa
Complicated urinary tract infections

- Intermittent administration

• IV: 100-150mg/kg/day, in 3 divided doses; Max: 6g/24hrs

Neutropenic children

- Intermittent administration

• IV: 150mg/kg/day, in 3 divided doses; Max: 6g/24hrs

Febrile neutropenia
Nosocomial pneumonia

- Continuous infusion

• IV: Loading dose: 60-100mg/kg; THEN 100-200mg/kg/day as a continuous infusion; Max: 6g/24hrs 

Older than 2 months and ≥40kg

• See adult dosage

Pregnancy

• Caution
• There are limited amounts of data from the use of ceftazidime in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development
• Ceftazidime should be prescribed to pregnant women only if the benefit outweighs the risk

Breastfeeding

• Compatible
• Ceftazidime is excreted in human milk in small quantities but at therapeutic doses of ceftazidime, no effects on the breastfed infant are anticipated. Ceftazidime can be used during breastfeeding

Fertility

• No data are available

Renal Impairment

• Caution; dose adjustment recommended
  An initial loading dose of 1000mg should be given. Maintenance doses should be based on creatinine clearance :

Recommended maintenance doses of Ceftazidime in renal impairment
- Intermittent infusion

CrCl (ml/min)	Approx. serum creatinine μmol/l (mg/dl)	Recommended dose of ceftazidime
		Adults and children ≥40kg	Children <40kg
31-50	150-200 (1.7-2.3)	1000mg, 12hrly	25mg/kg, 12hrly
16-30	200-350 (2.3-4.0)	1000mg, 24hrly	25mg/kg, 24hrly
6-15	350-500 (4.0-5.6)	500mg, 24hrly	12,5mg/kg, 24hrly
<5	>500 (>5.6)	500mg, 48hrly	12.5mg/kg, 48hrly
- In patients with severe infections the unit dose should be increased by 50% or the dosing frequency increased. In children, the creatinine clearance should be adjusted for body surface area or lean body mass - Children <40kg: The serum creatinine values are guideline values that may not indicate exactly the same degree of reduction for all patients with reduced renal function

- Continuous infusion

CrCl (ml/min)	Approx. serum creatinine μmol/l (mg/dl)	Frequency of dosing (hourly)
		Adults and children ≥40kg	Children <40kg
31-50	150-200 (1.7-2.3)	Loading dose: 2g; THEN 1-3g/24hrs	- Not established for use -Close clinical monitoring for safety and efficacy is advised - If continuous infusion is used in children with renal impairment, the creatinine clearance should be adjusted for body surface area or lean body mass
16-30	200-350 (2.3-4.0)	Loading dose: 2g; THEN 1g/24hrs
≤15	>350 (>4.0)	Not evaluated

• Haemodialysis and peritoneal dialysis: Caution; dose adjustment recommended
  See additional prescribing points for dose adjustment recommendations 

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no information available
  Close clinical monitoring for safety and efficacy is advised

Elderly

• Caution; dose adjustment recommended
• >80 years: Max: 3g/24hrs

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Headache
• Dizziness
• Neurological sequelae
  - Tremor
  - Myoclonia
  - Seizures
  - Encephalopathy
  - Coma
• Paraesthesia

Cardiovascular Disorders 

• Phlebitis (IV)
• Thrombophlebitis (IV)

Gastrointestinal Disorders 

• Diarrhoea
  - Antibacterial agent-associated diarrhoea (associated with clostridium difficile) 
• Colitis
  - Antibacterial agent-associated colitis (associated with clostridium difficile)
  - Pseudomembranous colitis
• Abdominal pain
• Nausea and vomiting
• Bad taste

Hepatobiliary Disorders 

• Transient elevation in hepatic enzymes
  - Alanine transaminase (Serum glutamic pyruvic transaminase)
  - Aspartate transaminase  (serum glutamic oxaloacetic transaminase)
  - Liver hydrolysate
  - Gamma-glutamyltransferase
  - Alkaline phosphatase
• Jaundice

Genitourinary Disorders 

• Transient elevations of blood urea, blood urea nitrogen and/or serum creatinine
• Interstitial nephritis
• Acute renal failure

Skin and Subcutaneous Tissue Disorders

• Maculopapular rash
• Urticarial rash
• Pruritus
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Angioedema
• Drug reaction with eosinophilia and systemic symptoms
• Pain and/or inflammation (IM)

Immune, Blood and Lymphatic System Disorders 

• Candidiasis  
  - Vaginitis
  - Oral thrush
• Eosinophilia
• Thrombocytosis
• Neutropenia
• Leucopenia
• Thrombocytopenia
• Agranulocytosis
• Haemolytic anaemia
• Lymphocytosis
• Anaphylaxis
  - Bronchospasm
  - Hypotension
• Fever
• Positive Coombs' test

• Nephrotoxic agents
• Aminoglycosides
• Potent diuretics
• Furosemide
• Chloramphenicol
• Probenecid

Other interactions

• Laboratory tests/ assays
  - Copper reduction methods, including Benedict's test, Fehling's test and Clinitest
  - Coombs' test 

None routine. Specific cases may require

• Renal function

Additional observations

• Signs and symptoms of anaphylaxis (during first dose)

Injection 1g, Injection 2g - EML (Hospital)

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Renal dose adjustments: Dialysis

Haemodialysis

• The serum half-life during haemodialysis ranges from 3-5hr. Following each haemodialysis period, the maintenance dose of ceftazidime recommended in the table below should be repeated

Peritoneal dialysis

• Ceftazidime may be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD). In addition to IV use, ceftazidime can be incorporated into the dialysis fluid (usually 125-250mg for 2 litres of dialysis solution). For patients in renal failure on continuous arterio-venous haemodialysis or high-flux haemofiltration in intensive therapy units: 1g daily either as a single dose or in divided doses. For low-flux haemofiltration, follow the dosage recommendations under Renal Impairment (under Special Populations)
• For patients on veno-venous haemofiltration and veno-venous haemodialysis, follow the dosage recommendations in the tables below

Continuous veno-venous haemofiltration dose guidelines 

Residual renal function (CrCl ml/min)	Maintenance dose (mg) for an ultrafiltration rate (ml/min) of:*
	5	16.7	33.3	50
0	250	250	500	500
5	250	250	500	500
10	250	500	500	750
15	250	500	500	750
20	500	500	500	750
*Maintenance dose to be administered 12hrly

Continuous veno-venous haemodialysis dose guidelines 

Residual renal function (CrCl ml/min)	Maintenance dose (mg) for a dialysate in flow rate of*:
	1.0 litre/hr			2.0 litre/hr
	Ultrafiltration rate (litres/h)
	0.5	1.0	2.0	0.5	1.0	2.0
0	500	500	500	500	500	750
5	500	500	750	500	500	750
10	500	500	750	500	750	1000
15	500	750	750	750	750	1000
20	750	750	1000	750	750	1000
*Maintenance dose to be administered 12hrly

Ceftazidime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.

Spectrum of activity: Some Gram-positive aerobes, such as Streptococcus pyogenes, Streptococcus agalactiae; Some Gram-negative aerobes, such as Citrobacter koseri, Haemophilus influenzae, Moraxella catarrhalis, Pasteurella multocida, Neisseria meningitidis, Proteus mirabilis, Proteus spp (other), Providencia spp.

Injection (per vial) 500mg

• Fortum (Sekpharma) originator
• Keftaz (Sandoz SA)
• Taziject (Acino Pharma)

Injection (per vial) 1g

• Ceftazidime 1g Oethmaan (Oethmaan Biosims) 
• Fortum (Sekpharma) originator
• Fresenius Ceftazidime (Fresenius Kabi)
• Keftaz (Sandoz SA)
• Orzid (Orchid)
• Taziject (Acino Pharma)

Injection (per vial) 2g

• Fortum (Sekpharma) originator
• Fresenius Ceftazidime (Fresenius Kabi)
• Keftaz (Sandoz SA)
• Orzid (Orchid)
• Taziject (Acino Pharma)