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0861 LANCET(526238)
Annual Surveillance Report & Antibiotic GuideSpecialists | 2017
CONTENTS01ESKAPE Organisms KwaZulu Natal Region: January 2016 to December 2016
Summary
02
02
03
06
07
09
11
11
13
15
16
16
19
20
23
24
24
25
26
Introduction
Blood Cultures
Invasive candidiasis
De�nitions
RESPIRATORY TRACT PATHOGENS
Bacterial
Viral
COMMON URINARY TRACT PATHOGENS
ANTIBIOTIC GUIDELINES
Trade names and route of administration
Dosages for Selected Antibiotics: Adults
Dosages for Selected Antibiotics: Paediatrics
Antibiotic dosages for upper respiratory tract infections
Dosages for ESBL positive Enterbacteriaceae
Prolonged infusion of Beta Lactam antibiotics
Dosages of prolonged infusions
REFERENCES
ESKAPE ORGANISMS KWAZULU NATAL REGION02
The following microorganisms, forming the acronym , have been listed among the most ESKAPE CCCprioritized antimicrobial resistance threats, effectively escaping the currently available antimicrobial armamentarium: E: Enterococcus faecium (Vancomycin resistant) S: Staphylococcus aureus (Methicillin resistant) K: Klebsiella species A: Acinetobacter baumannii (Carbapenem resistant) P: Pseudomonas aeruginosa (Carbapenem resistant) E: Enterobacter species C: Clostridium dif�cile C: Carbapenem resistant Enterobacteriaceae C: Candida species
Antimicrobial resistance (AMR) is a worldwide problem. New forms of AMR are crossing international boundaries and spreading between continents with ease and speed. World health leaders have described antibiotic resistant microorganisms as �nightmare bacteria� that �pose a catastrophic threat� to people in every country in the world. Antibiotic-resistant infections add considerable and avoidable costs to overburdened health care systems.
AMR estimates are an integral component of any antimicrobial stewardship program, allowing for informed appropriate selection of empiric therapy in an institute based on local epidemiology.
This report summarizes Lancet Laboratories AMR annual estimates for 2014 through to 2016 for the Kwa Zulu Natal private sector.
SUMMARY03
TABLE 1: ESKAPE pathogens KZN 2014 - 2016
Vancomycin resistant Enterococci (VRE)
Methicillin resistant S. aureus (MRSA)
Acinetobacter species � Carbapenem resistant (CRAc)
Pseudomonas aeruginosa �Carbapenem resistant (CRPs)
ESBL positive Enterobacteriaceae
Carbapenem resistant Enterobacteriaceae (CRE)
Candida species (non-albicans Candida/total Candida)
Fluconazole resistant Candida spp
Voriconazole resistant Candida spp
Echinocandin resistant Candida spp
0.8
18
38
33
28
0.9
77
81
44
0
0.1
13
50
23
34
0.9
75
84
53
0
0.3
9
54
26
36
1.7
77
79
53
0
ESKAPE PATHOGENS 2014% 2015% 2016%
VRE = Vancomycin resistant Enterococci
MRSA = Methicillin resistant Staphylococcus aureus
CRAc = Carbapenem resistant Acinetobacter species
CRPs = Carbapenem resistant Pseudomonas aeruginosa
ESBL = Extended spectrum beta-lactamase positive Enterobacteriaceae
CRE = Carbapenem resistant Enterobacteriaceae
C.dif�cile = Clostridium dif�cile
Candida spp = non-albicans Candida species
SUMMARY04
0
10
20
30
40
50
60
70
80
90
2016
2015
2014
VRE
MRSA
CRAc
CRPs
ESBL
CRE
C.d
ifficile
Can
dida
spe
cies
Per
cent
age
resi
stan
t is
ola
tes
Figure 1: Multidrug resistant pathogens (all clinical specimen types)
· VRE rates are low throughout the province. · MRSA rates have consistently decreased over the last 3 years, while ESBL rates have increased. · Carbapenem resistance among Acinetobacter species and Enterobacteriaceae (CRE) have progressively increased over the last 3 years · While these rates are consistent with national trends, it is nevertheless a cause for concern
SUMMARY05
Figure 2: ESBL producing Enterobacteriaceae (all sites)
· An increase in ESBL positive E. coli isolates is noted over the last 3 years, which is of concern as these are common causes of community-acquired urinary tract infections. · ESBL rates among other Enterobacteriaceae have remained stable.
0
10
20
30
40
50
60
E.coli Klebsiella species Other
26 27 28
50 49 51
29 31 32
Enterobacteriaceae species
Pec
enta
ge
ES
BL
po
siti
ve is
ola
tes
2016
2015
2014
90107
130
258
0
50
100
150
200
250
300
2013 2014 2015 2016
Nu
mb
er o
f is
ola
tes
Carbapenem resistant Enterobacteriaceae (CRE) by year
Figure 3: Carbapenem resistant Enterobacteriaceae (clinical specimens) · There has been a dramatic increase in the number of CRE isolated in this province over the last year. Active surveillance for these pathogens, robust antimicrobial stewardship programs and meticulous infection control practices are useful interventions in addressing this problem.
BLOOD CULTURES06
2015 2016
Table 2: The �ve most frequently isolated species from blood cultures, in rank order, for 2015 and 2016 in KZN private hospitals
· Pseudomonas species has replaced Enterococcus species among the top �ve bacteraemia organisms in 2016. · The concurrent increase in carbapenem-resistant Pseudomonas aeruginosa bacteraemia, 16% (14/88) to 20% (19/95) from 2015 to 2016, makes this a cause for concern. · Candida species remain the 4 th most common organism isolated from blood cultures. This is of concern as Candidaemia is associated with very high mortality rates.
Figure 4: Resistant isolates (2015 and 2016). blood culture
· The rates of resistant bacteria in blood cultures is similar to that in all clinical specimens (Figure 1). · ESBL positive E. coli bacteraemia can be dif�cult to treat as these isolates are often resistant to other antimicrobials, such as �uoroquinolones e.g. cipro�oxacin. · The decrease in MRSA rates is reassuring. · The increase in invasive candidiasis is of concern.
2015 2016
E. coli
Staphylococcus aureus
Klebsiella pneumoniae
Candida species
Enterococcus species
E. coli
Klebsiella pneumoniae
Staphylococcus aureus
Candida species
Pseudomonas aeruginosa
32
48
20
77
28
50
9
86
0
10
20
30
40
50
60
70
80
90
100
ESBL E.coli ESBL K.pneumoniae MRSA Candida species
Per
cen
tag
e re
sist
ant
isol
ates
INVASIVE CANDIDIASIS07
2014
2016
2015
C.albicans
C.parapsilosis
C.glabrata
C.krusei
C.auris
C.haemulonii
C.species
20
56
15
2
7
24
55
14
1
6
23
50
16
1 1 2
810
20
30
40
50
60
Per
cen
tag
e o
f is
ola
tes
0 00 00
Figure 5a: Species distribution (%) of Candida isolates from sterile sites (blood cultures and catheter tips).
· The predominant species is C. parapsilosis. · There has also been an emergence of in the province and country. This species is C. auris often azole resistant and can be resistant to echinocandins e.g. caspofungin, micafungin
INVASIVE CANDIDIASIS08
Fluconazole R
8184
79
2014
2016
2015
44
0
53
0
53
00
10
20
30
40
50
60
70
80
90
Voriconazole R Echinocandin R
Per
cen
tag
e re
sist
ant
isol
ates
Antifungal agents
Figure 5b: Antifungal resistance in Candida species (non-albicans) (blood cultures and catheter tips)
· More than 50% of non-albicans Candida species are resistant to the azoles, �uconazole and voriconazole, which makes these agents inappropriate for empiric therapy where invasive candidiasis is suspected in this province. · Echinocandin resistance has not been detected in this province, to date. · The empiric therapy choices for suspected invasive candidiasis remain an echinocandin or amphotericin B.
Dé�nitions :
Vancomycin resistant (VRE) Enterococci Enterococci cause a range of illnesses, which includes bloodstream infections, surgical site infections, and urinary tract infections. Methicillin resistant (MRSA): MRSA is de�ned as Staphylococcus aureus that has S. aureustested resistant (R) to at least 1 of the following: methicillin, oxacillin, cefoxitin. These isolates are resistant to penicillin, beta-lactam/beta-lactam inhibitor combinations, cephalosporins (except those cepbalosporins speci�cally indicated for MRSA) and carbapenems.
Acinetobacter species: (CRAc = carbapenem resistant Acinetobacter species) Acinetobacter species are gram-negative bacteria that can cause pneumonia or bloodstream infections among critically ill patients. Acinetobacter species have developed resistance to nearly all antibiotic classes, including carbapenems, often considered antibiotics of last resort. Antimicrobial susceptibility results must guide therapy. Carbapenem-Resistant Acinetobacter spp. = any Acinetobacter spp. that has tested either intermediate (I) or resistant (R) to at least one of the following: imipenem, meropenem, doripenem Pseudomonas aeruginosa: (CRPs = carbapenem resistant Pseudomonas aeruginosa) Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream infections, urinary tract infections, and surgical site infections. Some strains of Pseudomonas aeruginosa have been found to be resistant to nearly all antibiotic classes including aminoglycosides, cephalosporins, �uoroquinolones, and carbapenems. Carbapenem-Resistant Pseudomonas aeruginosa = any Pseudomonas aeruginosa that has tested either intermediate (I) or resistant (R) to at least 1 of the following: imipenem, meropenem, or doripenem. Enterobacteriaceae � The three most common types of Enterobacteriaceae causing healthcare associated infections include Enterobacter spp., Klebsiella spp., and E. coli. These bacteria cause pneumonia, urinary tract infections, and bloodstream infections. Extended spectrum beta lactamase (ESBL) production and carbapenemase (carbapenem resistant Enterobacteriaceae � CRE) production should be noted when selecting optimal antimicrobial therapy.
Extended spectrum beta lactamase producing (ESBL Positive) Entrobacteriaceae Extended spectrum beta-lactamases (ESBL) are enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Infections with ESBL-producing organisms have been associated with poor outcomes. Carbapenems (meropenem, doripenem, imipenem and ertapenem) are the antimicrobial agents of choice for infections caused by such organisms.
Carbapenemase resistant Enterobacteriaceae (CRE) Carbapenem resistant Enterobacteriaceae (CRE) are isolates that are resistant to the carbapenems. CRE are often resistant to multiple classes of antimicrobials substantially limiting treatment options. Infections caused by CRE are associated with high mortality rates.
DEFINITIONS09
Many CRE possess carbapenemases (carbapenemase producing Enterobacteriaceae (CPE)) which can be transmitted from one Enterobacteriaceae to another potentially facilitating transmission of resistance. Untreatable and hard-to-treat infections from carbapenem-resistant Enterobacteriaceae (CRE) bacteria are on the rise among patients in medical facilities. CRE have become resistant to all or nearly all the antibiotics we have today. Almost half of hospital patients who get bloodstream infections from CRE bacteria die from the infection. Therapeutic options include a combination of colistin and tigecycline or any other antibiotic to which the organism is susceptible.
Clostridium dif�cile: Clostridium dif�cile (C. dif�cile) infections can cause illness ranging from diarrhoea to antibiotic-associated colitis, which can be fatal. These infections mostly occur in people who have had both recent medical care and antibiotics. Often, C. dif�cile infections occur in hospitalized or recently hospitalized patients.
DEFINITIONS10
Most respiratory tract infections are viral in aetiology, thus requiring no antibiotic therapy. Bacterial infections may complicate these. The following �gures highlight the common pathogens detected in KZN in 2016.
Viral
Figure 6a: Respiratory viruses plus Mycoplasma pneumoniae as detected on polymerase chain reaction (PCR) for 2016. · was the most frequently detected viral respiratory pathogen. It was detected Rhinovirus consistently throughout the year. It is associated with prolonged hospitalisation and increased risk for the development of asthma. · was the third most frequently detected organism indicating its Mycoplasma pneumoniae importance as part of the differential diagnosis when presented with an atypical pneumonia. · is an important pathogen in both children and adults, presenting with Adenovirus conditions ranging from conjunctivitis and pharyngitis to pneumonia and life-threatening systemic infections. It is present at consistent levels throughout the year.
Rhino
viru
s
RSV
M. p
neum
oniae
Adeno
viru
s
Influ
enza
A
PIV (1
-4)
Influ
enza
B
Oth
er (P
arec
hoviru
s an
d Boc
aviru
s)
hMPV
Enter
oviru
s
hCoV
(Oc4
3, 2
29E, N
l63,
HKU
1)
0
100
200
300
400
500
600
700
800
900 856
753
517
453
375 370
254 254224 223
190
Num
ber
of
po
siti
ves
on
PC
R
RESPIRATORY TRACT PATHOGENS 11
RESPIRATORY TRACT PATHOGENS12
Figure 6b: Seasonal distribution of respiratory viruses in 2016 (PCR). · was detected throughout the year, but infections peaked over February-April. RSV A second smaller peak was noted over November-December 2016. This second peak falls outside the period over which palivizumab (Synergis®) is usually given to premature infants for the prevention of RSV infection. · The season was prolonged in 2016 and atypical in that the initial peak was due to in�uenza in�uenza B, followed by in�uenza A. In preceding years, the reverse has been the norm. Cases of in�uenza B were early as March, increasing from May, and peaking in June. Cases of in�uenza B infection were detected into November. In�uenza A cases were also detected in March, but increased over the months of June-August. Cases of in�uenza A infection were also detected into November. The in�uenza A cases were a mixture of subtype H3N1 and H1N1.
Jan-
16
Feb-1
6
Mar
-16
Apr-16
May
-16
Jun-
16
Jul-1
6
Aug-1
6
Sep-1
6
Oct-1
6
Nov-1
6
Dec-1
60
50
100
150
200
250
300
350
400
Num
ber
of
po
siti
ves
on
PC
R
In�uenza A In�uenza B Rhinovirus RSV Adenovirus
RESPIRATORY TRACT PATHOGENS13
Bacterial
Figure 7a: Streptococcus pneumoniae, Haemophilus parain�uenzae and Haemophilus in�uenzae in 2016. · The commonest bacterial pathogens are H. in�uenzae and Streptococcus pneumoniae. Haemophilus parain�uenzae is a commensal of the nasopharynx but has also been implicated in respiratory tract infections, such as pneumonia and sinusitis.
Figure 7b: Specimen source distribution of Streptococcus pneumoniae, Haemophilus parain�uenzae and Haemophilus in�uenzae isolates in 2016. · The predominant specimen type was sputum/endotracheal aspirates. · Twenty-four percent of S. pneumoniae isolates were from blood cultures.
277288302
8051059
1105
828873
1072
2014 2015 2016
0 200 400 600 800 1000 1200
Number of isolates
S. PNEUMONIAE
H. PARAINFLUENZAE
H. INFLUENZAE
619
49
59
98
2
00
0
10
85
224
0 20 40 60 80 100 120
STREPTOCOCCUS PNEUMONIAE
HAEMOPHILUS PARAINFLUENZAE
HAEMOPHILUS INFLUENZAE
BLD CSF LRT ENT OTHER
RESPIRATORY TRACT PATHOGENS14
Figure 7c: Percentage of S. pneumoniae isolates, from all sites or blood, that were non-susceptible to penicillin, macrolides and quinolones, and percent of H. in�uenzae and H. parain�uenzae that were non-susceptible to quinolones. · The common bacterial respiratory pathogens H. in�uenzae and S. pneumoniae were susceptible to amoxyclavulanic acid (>99%). · Less than 5% of S. pneumoniae isolates, from blood and all sites, were non-susceptible to penicillin and quinolones. · Note level of macrolide resistance in S.pneumoniae.
Penicillin non-susceptible S. pneumoniae (all sites)
Penicillin non-susceptible S. pneumoniae (blood)
Macrolide R S.pneumoniae (all sites)
Macrolide R S.pneumoniae (blood)
Quinolone R S.pneumoniae (all sites)
Quinolone R S.pneumoniae (blood)
Quinolone R H. parain�uenzae
Quinolone R H. in�uenzae
0 5 10 15 20 25 30 35 40 45
Percent non-susceptible isolates
2014 2015 2016
E. coli remains the commonest cause of community acquired urinary tract infections in the province.
Figure 8: Percentage of Cipro�oxacin susceptible and ESBL positive E. coli urinary isolates from 2012 � 2016.
· The percentage of cipro�oxacin susceptible isolates have dropped to below 60% in 5 years, and the rate of ESBL positivity, and therefore resistance to most beta-lactams and cephalosporins, has increased signi�cantly from 17 to 26%. · This is of concern as an increasing proportion of patients with community-acquired urinary tract infections may require parenteral antimicrobials. · The high level of susceptibility to urinary antiseptics such as fosfomycin and nitrofurantoin make these agents suitable for the treatment of uncomplicated cystitis. · Patients with suspected pyelonephritis, however, will require investigations such as urine for microscopy and culture, and/or admission for parenteral antimicrobials, as guided by antimicrobial susceptibility test results
COMMON URINARY TRACT PATHOGENS15
Ertapenem SFosfomycin SNitrofurantoin SCipro�oxacin SESBL positive
Per
cen
tag
e E
.col
i uri
nar
y is
olat
es
0
20
40
60
80
100
120
2012 2016
ANTIBIOTIC GUIDELINES 16
Trade names and route of administration
Benzyl penicillin Procaine benzylpenicillin Benzathine penicillin Phenoxymethyl penicillin Amoxicillin Ampicillin Piperacillin Cloxacillin Amoxicillin/�ucloxacillin
GENERIC NAME TRADE NAMES ROUTE OF ADMINISTRATION
PENCILLINS
Novopen, Bio-pen Biocillin Penilente Betapen,Len V.K Amoxil, Betamox Petercillin,Ranamp Piperacillin Cloxin,Floxapen Suprapen,Macropen
im, iv im im p.o p.o p.o, im, iv im, iv po, im, iv po
Amoxicillin clavulanate Piperacillin-Tazobactam
ß LACTAM - ß LACTAMASE INHIBITORS
Augmentin Tazocin,Tazobax
p.o, iv iv
Cefadroxil Cefalexin Cefalothin Cefazolin Cephadrine
CEPHALOSPORINS 1ST GENERATION
Dacef / Cipadur Belex Ke�in Kefzol Cefril
p.o p.o iv im, iv p.o, im, iv
CEPHALOSPORINS 2ND GENERATION
Cefamandole Cefoxitin Cefprozil Cefuroxine
Mandokef Cefoxitin ProzefZinnat/Zinacef
im, iv im, iv p.op.o, im, iv
CEPHALOSPORINS 3RD GENERATION
Cefpodoxine Ce�xime Cefotaxime Ceftriaxone Ceftazidime
Orelox Fixime Cefotaxime Rocephin Fortum
p.o p.o im, iv im, iv im, iv
Cefepime Cefpirome
Maxipime Cefrom
im,iv iv
CEPHALOSPORINS 4TH GENERATION
Zinforo iv
CEPHALOSPORINS 5TH GENERATION
Ceftaroline
ANTIBIOTIC GUIDELINES 17
Imipenem Meropenem Doripenem Ertapenem
GENERIC NAME TRADE NAMES ROUTE OF ADMINISTRATION
CARBAPENEMS
Tienam Meronem Doribax Invanz
iv iv iv im, iv
Wintomylon po
QUINOLONES - 1ST GENERATION
Nalidixic acid
Cipro�oxacin Enoxacin Levo�oxacin Lome�oxacin Nor�oxacin O�oxacin
QUINOLONES - 2ND GENERATION
Ciprobay Bactidron Tavanic Maxaquin Utin Tarivid
p.o, iv p.o p.o, iv p.o p.o p.o, iv
Gemi�oxacin Moxi�oxacin
QUINOLONES - 3RD GENERATION
Factive Avelon
p.o p.o, iv
Erythromycin Roxyithromycin Clarithromycin Azithromycin Telithromycin
MACROLIDES/LINCOSAMIDES/KETOLIDE
Ilosone Rulide Klacid Zithromax Ketek
p.o, iv p.o p.o.iv p.o, iv p.o
Tetracycline Doxycycline Minocycline
TETRACYCLINES
Tetracyclines Doxycyl, Cyclidox Cyclimycin
p.o p.o p.o
Dalacin p.o, im, iv
LINCOSAMIDES
Clindamycin
Amikacin Gentamycin
AMINOGLYCOSIDES
Amikacin Garamycin
im, iv im, iv
Teicoplanin Vancomycin
GLYCOPEPTIDES
Targocid,Teicowin Vancocin
im, iv im, iv
ANTIBIOTIC GUIDELINES 18
Metronidazole Cotrimoxazole Fusidic Acid Nitrofurantoin Colistin Aztreonam Linezolid Fosfomycin Daptomycin
GENERIC NAME TRADE NAMES ROUTE OF ADMINISTRATION
OTHER
Flagyl Purbac/ Bactrim Fucidin Macrodantin Azactam Zyvoxid Urizone Cubicin
p.o, iv p.o, iv p.o, iv p.o iv iv iv po
Amphotericin B Clotrimazole Fluconazole Griseofulvin Ketoconazole Itraconazole Voriconazole Posaconazole Caspofungin AnidulafunginMicafungin
ANTIFUNGALS
Fungizone Canesten Di�ucan Folan Nizoral Sporanox Vfend Noxa�l Cancidas Eraxis Mycamine
iv p.o (troche) p.o, iv p.o p.o p.o p.o, iv p.o iv iviv
ANTIBIOTIC DOSAGES19
Dosages for Selected Antibiotics: Adults
ANTIMICROBIAL CLASS
ANTIMICROBIAL AGENT LOADING DOSE DOSE
Carbapenem Ertapenem
Imipenem
Meropenem
Doripenem
1 g daily (up to 1g bd)
1 -2g/day 6-8 hourly, infuse over 40-60 minutes
1-2g 8 hourly, infuse over 30 minutes
500mg 8 hourly, infuse over 60 minutes
Aminoglycosides Gentamicin
Amikacin
5-6mg/kg/day, once daily
15mg/kg/day, once daily
Beta-lactam beta-lactamase combination
Piperacillin-tazobactam
4.5g 6 hourly
Glycylcycline Tigecycline 50mg 12hourly (higher doses may be considered)
Polymyxin Colistin 4.5MIU 12 hourly 9MIU IVI
Glycopeptides Vancomycin
Teicoplanin
15-20mg/kg 12 hourly
6-12mg/kg 12 hourly x 3-5 doses followed by 6mg/kg daily
Lipopeptide Daptomycin 6-8(up to 12)mg/kg/day once daily
Azoles Voriconazole 3-4mg/kg 12 hourly 6mg/kg 12hourly for 24 hours
Echinocandins Caspofungin
Anidulafungin
Micafungin
50mg once daily thereafter
100mg once daily thereafter
100mg IVI once daily
70mg IVI on the �rst day
200mg IVI on the �rst day
ANTIBIOTIC DOSAGES20
Dosages for Selected Antibiotics: Paediatrics
ANTIMICROBIAL CLASS
ANTIMICROBIAL AGENT
LOADING DOSE DOSE
MAXIMUMDOSEAGE
Carbapenem 15mg/kg IV/IM 12 hourly1g/day IV/IM up to 14 days
Ertapenem 3-12 years>12 years
1g/day
25mg/kg/dose 12 hourly in the 1st week of life, 8 hourly from 1-3 weeks and 6hourly thereafter
Imipenem Neonates (>1.5kg)
15-25mg/kg 6 hourly, infuse over 30 minutes
Infants and children >3
months
2g/day
10-20mg/kg/dose 8 hourly, infuse over 5-30minutes
Meropenem >3months
As for adults >50kg
Aminoglycosides 8mg/kg/day on 1 st day; 6mg/kg/day thereafter
Gentamicin 1week � 10years
1g/day
7mg/kg/day on 1 st day; 5mg/kg/day thereafter
>10years
15mg/kg/dose daily 18mg/kg/dose daily thereafter
Neonates 1 week-10years
15mg/kg/dose daily thereafter
Amikacin
>10years
360mg/day
25mg/kg/dose on 1st day
20mg/kg/dose on 1st day
Beta-lactam beta-lactamase inhibitor combination:
100mg/kg/dose 12 hourly Piperacillin/tazobactam
Neonates≤7days
100mg/kg/dose 8 hourly 8-28days
150 � 300mg/kg/24 hours in 3 to 4 divided doses
Infant < 6 months
300 � 400mg/kg/24 hours in 3 to 4 divided doses
Infant >6 months
Glycylcycline 1.2mg/kg/dose 12 hourly Tigecycline 8-11years (limited data)
1mg/kg/dose 12 hourly ≤12years (limited data)
50mg/dose
1.5mg/kg/dose (max
100mg/dose)
ANTIBIOTIC DOSAGES21
Dosages for Selected Antibiotics: Paediatrics
ANTIMICROBIAL CLASS
ANTIMICROBIAL AGENT
LOADING DOSE DOSE
MAXIMUMDOSEAGE
5 th Generation cephalosporin
8mg/kg/dose 8 hourly Ceftaroline (complicated skin infections and bacterial community-acquired pneumonia)
2-6months
12mg/kg/dose 8 hourly 400mg/dose 8 hourly
>6months <18years:
≤33kg>33kg
Polymyxin Colisitin Neonates≤7days>7days
2.5 � 5mg/kg/day in 2 to 4 divided doses
Child 7mg/kg/day
Lipopeptide 9mg/kg daily Daptomycin (skin and skin structure infections)
2-6 years
7mg/kg daily 7-11 years
5mg/kg daily 12 � 17 years
Glycopeptide 10mg/kg 12 hourly replave with vancomycin
1 week
10mg/kg 8 hourly 1 week-1 month
15mg/kg 6 hourly, infuse over 60 minutes
>1 month
Neonates
>2months-≤12years
15mg/kg
15mg/kg
16mg/kg
10mg/kg 12 hourly for
3 doses
8mg/kg daily
6 - 10mg/kg daily
Oxazolidinone 10mg/kg 8 hourly, IV or POLinezolid
Azoles 4mg/kg 12 hourly Voriconazole 2-12 years 6mg/kg 12 hourly
for 2 doses
Teicoplanin
22
Dosages for Selected Antibiotics: Paediatrics
ANTIMICROBIAL CLASS
ANTIMICROBIAL AGENT
LOADING DOSE DOSE
MAXIMUMDOSEAGE
Echinocandins 50 mg/m² from day 2 onwards [Equation: BSA (m2) = SQR RT ([Height (cm) x Weight (kg)]/ 3600)]
Caspofungin 70 mg/m² on day 1
Neonate and infant
70mg (regardless of the patient�s calculated dose)
Anidulafungin 1.5mg/kg/dose daily
Child 0.75 � 1.5 mg/kg/dose daily
Micafungin Neonates and
children <4 months
4-10mg/kg/day
Infants >4 months,
children, and
adolescents
2mg/kg daily 100mg/dose
ANTIBIOTIC DOSAGES
23 ANTIBIOTIC DOSAGES
A) Acute Pharyngotonsillitis Adults Paediatrics
1.Amoxicillin 500 - 1000mg twice daily, OR, 50mg/kg/day once daily (maximum 3000mg) for 10 days
50mg/kg/d once daily (maximum 1000 mg) for 10 days.
2.If penicillin allergic: a) Azithromycin b) Clarithromycin
500 mg once daily for 3 days.
500 mg twice daily or 500 mg modi�ed-release once daily for 10 days.
10 - 20 mg/kg/d once daily for 5 days. 15 mg/kg/d divided into 2 doses, for 10 days.
Antibiotic dosages for upper respiratory tract infections
B)AOM or ABRS Adults Paediatrics
1.Amoxicillin 1 g 8 hourly for 5 days. 80 - 90 mg/kg/d divided into 2 doses. <2 years 7days >2 years 5days
Amoxicillin-clavulanate 2000 mg amoxicillin - 125 mg clavulanate 12 hourly for 5 days.
90 mg/kg/d
Cefuroxime 1000 mg 12 hourly for 5 days. 30 mg/kg/d divided into 2 doses.
Cefpodoxime 400 mg 12 hourly for 5 days. 16 mg/kg/d divided into 2 doses.<2 years 7 days >2 years 5 days
2. If penicillin allergic: a) Azithromycin b) Clarithromycin
c) Erythromycin estolate d) Levo�oxacin
e) Telithromycin f) Gemi�oxacin g) Moxi�oxacin
500 mg 12 hourly or 750 mg once daily for 5 days. 800 mg once daily for 5 days. 320 mg once daily for 5 days. 400 mg once daily for 5 days.
10 mg/kg once daily for 3 days. 15 � 30 mg/kg/d divided into 2 doses for 5 days. 40 mg/kg/d divided into 4 doses for 5 days. 20 mg/kg/d once daily or divided into 2 doses for 5 days.
Adapted from: Brink A, et al. Updated recommendations for the management of upper respiratory tract infections in South Africa. S Afr Med J 2015
AOM(acute otitis media) and ABRS ( acute bronchial rhinosinusitis)
24 ANTIBIOTIC DOSAGES
Dosages for ESBL positive Enterobacteriaceae Adapted from Bassetti M, etal. The Management of Multidrug-resistant Enterobacteriaceae. www.co-infectiousdiseases.com; 2016
Primary BSI Pneumonia Abdominal infection Urinary tract Infection
First-line therapy: Pip/tazo MIC�16/4mg/l Piperacillin-Tazobactam 16/2 g every 24 h (a) Meropenem 1 g 6 hourly (b) or ertapenem 500mg 6 hourly (c) or imipenem 0.5 g 6 hourly (d) or imipenem 1 g 8 hourly
As for BSIs As for BSIs Tigecycline 50 mg 12 hourly (e)
As for BSIs
Second-line therapy Carbapenems i.v. + amikacin 15-20 mg/kg /day daily or tigecycline 50 mg every 12 hourly Enterobacteriaceae PTZ MIC>16/4mg/l and/ or severe infection. Meropenem 1 g 6 hourly (b) or ertapenem 500 mg 6 hourly (c) or imipenem 0.5 g 6 hourly (d) or imipenem 1 g 8 hourly
As for BSIs Carbapenems i.v. +amikacin 15 � 20 mg/kg/day daily
As for BSIs
As for BSIs
As for BSIs As for BSIs
a) Piperacillin/tazobactam: loading dose (4.5g in 1 h) followed by maintenance doses with continuous infusion (16/2 g every 24 h). b) Meropenem: loading dose (1 g over 1 h) followed by maintenance doses with continuous infusion (1 g every 6 h over 6 h). c) Ertapenem: maintenance doses with continuous infusion (500 mg every 6 h over 4 h) d) Imipenem: loading dose (0.5 or 1 g over 1 h) followed by maintenance dose with continuous infusion (0.5 g every 6 h or 1 g every 8 h over 2 h). e) Tigecycline: loading dose (100 mg every 12 h) if tigecycline MIC 0.5 � 1mg/l.
PROLONGED INFUSION OF BETA LACTAM ANTIBIOTICS
The trend in increasing antimicrobial resistance and the dearth of new antibiotics necessitates the optimisation of beta lactam therapy. Since beta lactam antibiotics demonstrate time dependent killing of bacteria i.e. the time that free drug concentrations remain above MIC (ft>MIC) becomes a better predictor of killing. When giving intravenously, beta-lactams can be administered by three basic strategies. The most prevalent is the traditional intermittent schedule, which involves infusion of each fraction of the daily dosage over a short time intervals, i.e., 5 to 60 min. When each fraction of the daily dosage is infused over three or more hours, this dosing strategy is referred to as prolonged or extended infusion. A review of the literature suggests that prolonged or extended dosing of beta lactam antibiotics would be most bene�cial in patients with the serious infections.
25
Imipenem >7041 to 7021 to 40 6 to 20 or intermittentHD or PD CRRT
500 mg or 1 g500 mg or 750 mg250 or 500 mg250 or 500 mg
500 mg
Every 6 hours Every 8 hoursEvery 6 hours Every 12 hours
Every 6 hours
3 hours 3 hours 3 hours 3 hours
3 hours
Doripenem �50 mL/min30 to 50 mL/min 10 to 30 mL/min
500mg 250mg250mg
Every 8 hoursEvery 8 hoursEvery 12 hours
4 hours 1 hour for nosocomial pneumonia, complicated intra-abdominal infection/UTI (including pyelonephritis)
ANTIBIOTIC DOSAGES
Dosages for Prolonged infusions
Adapted from: Nicolau D, et al.Continous and Prolonged Intravenous ß-Lactam Dosing: Implications for the Clinical Laboratory. Clin Microbiol Rev. 2016 Oct;29(4):759-72. doi: 10.1128/CMR.00022-16.2016 Oct;29(4):759-72.
Antimicrobial agent
Piperacillin-tazobactam
Creatinine clearance
>20 mL/min �20 mL/min orintermittent HD or PDCRRT
Dose
3.375 or 4.5 g3.375 or 4.5 g
3.375 or 4.5 g
Dosing interval
Every 8 hours Every 12 hours
Every 8 hours
Infusion time
4 hours 4 hours
4 hours
Cefepime �50 mL/min30 to 49 mL/min 15 to 29 mL/min <15 mL/min or intermittent HD CRRT
2 g2 g1 g1 g
2 g
Every 8 hours Every 12 hours Every 12 hoursEvery 24 hours
Every 12 hours
4 hours 4 hours 4 hours4 hours
4 hours
Meropenem �50 mL/min 25 to 49 mL/min 10 to 24 mL/min <10 mL/min or intermittent HD CRRT
1 or 2 g 1 or 2 g 500 mg or 1 g 500 mg or 1 g
1 or 2 g
Every 8 hours Every 12 hours Every 12 hoursEvery 24 hoursgiven after HD Every 12 hours
3 hours 3 hours 3 hours 3 hours
3 hours
HD: haemodialysis; PD: peritoneal dialysis; CRRT: continuous renal replacement therapy; MIC: minimum inhibitory concentration; CVVHDF: continuous venovenous hemodia�ltration
1. South African Medicines Formulary, 11 th Edition 2. Wertheim H, et al. Global survey of polymyxin use: A call for international guidelines. J Global Antimicrob Resist (2013), http://dx.doi.org/10.1016/j.jgar.2013.03.012 3. Ulldemolins M et al. Antibiotic dosing in multiple organ dysfunction syndromeChest 2011; 139; 1210-1220 4. Bassetti M, etal. The Management of Multidrug-resistant Enterobacteriaceae. www.co- infectiousdiseases.com; 2016; 583-594 5. David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc, https://expertconsult.inkling.com/read/mcmillan-harriet-lane-handbook-pediatric- antimicrobial-2nd/chapter 6. Moehring R, et al. Prolonged Infusions of beta-lactam Antibiotics. UpToDate, accessed 10/02/2017. 7. Brink A, et al. Updated recommendations for the management of upper respiratory tract infections in South Africa. S Afr Med J 2015; 105(5):345-352. DOI:10.7196/SAMJ.8716 8. Communicable diseases surveillance bulletin, Volume 13. No 1 April 2015 9. Antibiotic resistance threats in the United States 2013, CDC 10.Antibiotic Resistance Patient Safety Atlas Phenotype De�nitions, CDC 2015; http://www.cdc.gov/hai/surveillance 11.Performance Standards for Antimicrobial Susceptibility Testing, 26th Edition, CLSI, 2016 12.Francesco G. De Rosa et al. From ESKAPE to ESCAPE to CCC; CID 2015:60 (15 April) 1289 13.Nicolau D, et al. Continous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory. Clin Microbiol Rev. 2016 Oct;29(4):759-72. doi: 10.1128/CMR.00022-16.2016 Oct;29(4):759-72. 14.Roberts JA, et al. Right Dose, Right Now: Customized Drug Dosing in the Critically Ill. Crit Care Med. 2017 Feb;45(2):331-336. doi: 10.1097/CCM.0000000000002210.
26 REFERENCES
? ! For further information please contact : Dr AKC Peer, Dr CN Govind or Dr K Moodley on 031 308 6500
These guidelines are based on current literature reviews and the expert opinion of Lancet microbiologists . The authors have made every effort to provide accurate information. However, they are not responsible for any errors, omissions, or for any outcomes related to the use of the contents of this book. Treatments and side effects described here may not be applicable to all patients; likewise, some patients may require a dose not described herein.
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