Professional Documents
Culture Documents
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http://ha.home/ho/ps/impact.pdf
Second edition: 2001 (ver 2.0), 2002 (ver 2.1), 2003 (ver 2.2)
First edition: 1999
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NOTICE
This publication contains information relating to
general principles of medical care, which should not be
construed as specific instructions for individual patients.
Manufacturers' product information and package inserts
should be reviewed for the latest information,
including contraindications, dosages and precautions. The editors, the
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information in this document and make no warranty, express or
implied, with respect to the currency, accuracy, or completeness of the
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health care professionals. Readers are reminded that some products
may not be available in their instutues.
Co-chairpersons
Dr. Raymond Wai Hung, Head, Infection Control Branch,
YUNG Centre for Health Protection,
Department of Health
Members (alphabetical
order)
Vancomycin .....................................................................................38
Quinupristin/dalfopristin and linezolid ............................................43
Ceftazidime......................................................................................45
Imipienem/meropenem/ertapenem ..................................................48
Once daily aminoglycosides..............................................................50
Summary of selected antifungal agents ............................................54
Table 1. Top ten isolates from clinical specimens in 2004 (data from a
regional hospital in Hong Kong). .......................................... 14
Table 2. Intrinsic and associated resistance to antimicrobial agents
among five nosocomial pathogens. ....................................... 15
Table 3. Methods to implement antimicrobial control......................... 28
Table 4. Potential barriers to reaching the strategic goals .................. 29
Table 5. Summary of published data on antimicrobial strategies as an
intervention to reduce ESBL resistance................................ 33
Table 6. Strategies for optimization of antimicrobial therapy .............. 36
Table 7. Dosage table for vancomycin................................................ 41
Table 8. Calculation of vancomycin dose for morbidly obese patient... 42
Table 9. Comparison of linezolid and quinupristin/dalfopristin.......... 44
Table 10. Hartford Hospital once-daily aminoglycoside normogram for
gentamicin and tobramycin ................................................. 53
Table 11. General patterns of antifungal susceptibility ...................... 54
Table 12. Comparison of susceptibility of selected fungi to the azoles 55
Table 13. Mechanisms of antifungal action........................................ 56
Table 14. Comparison of selected pharmacokinetic parameters for the
azoles and caspofungin ...................................................... 57
Table 15. A suggested scheme for systemic antifungal agents ............ 58
Table 16. Criteria for severity assessment of acute pancreatitis ......... 72
Table 17. Prophylactic use of antibiotic in acute pancreatitis ............. 73
Table 18. Comparative activities of commonly used beta-lactams
against Streptococcus pneumoniae with different levels of
penicillin susceptibility....................................................... 80
In Hong Kong, our long-term battle against antibiotic resistance continues and
antimicrobial guideline is an essential tool to promote rational use of
antimicrobial agents with better application of existing knowledge and adherence
to good practice.
The IMPACT was developed in 1999 as a first step towards better control of the
growing problem of antimicrobial resistance in Hong Kong. Developed with a
multidisciplinary approach with inputs from different specialties and institutions,
the IMPACT took into account the local data on prevalence of different pathogens
and antimicrobial resistance patterns.
Now into its third edition, the IMPACT has incorporated constructive comments
from clinicians and other colleagues as part of an on-going effort to keep abreast
of new antibiotics, changing resistance patterns and literature. This specifically
developed guideline for practitioners in Hong Kong provides evidence-based
principles focused on situations in which antimicrobial therapy could be
curtailed without compromising patient care.
The third edition of the IMPACT is a timely update to coincide with the launching
of the Antibiotic Stewardship Programme by the Hospital Authority which
includes optimal selection, dose and duration of treatment, as well as control of
antibiotic use. The IMPACT constitutes an essential element along with other key
elements of education, user-feedback, regular updates, clinical audits and
process evaluation in this comprehensive Programme.
I thank the many individuals and organizations who have contributed to the
compilation of IMPACT and look forward to your continued support and
partnership in our Antibiotic Stewardship Programme.
Dr Cheung Wai-lun
Director
Professional Services and Operations
Hospital Authority
This new edition updates and revises all the information in the
previous edition. The document is now organized into eight parts. Part
1 and II covers the background information. Part III provides
guidelines on the use of six classes of antibiotics. They are discussed
separately because they represent new agents (linezolid, quinupristin-
dalfopristin), agents in which usage has a strong link to development
of multidrug-resistant organisms (glycopeptides, ceftazidime, and
carbapenems) or that the dosing and monitoring are complicated
(aminoglycosides). Several new sections have been added:
antimicrobial stewardship programme, severe acute pancreatitis,
antifungal agents, and antibiotic dosing for CAPD peritonitis. The font
size and the print-out size have been increased to enhance readability.
A full list of tables and a quick reference are added to facilitate the use
of this book.
PL Ho
SSY Wong
November 2005
Table 1. Top ten isolates from clinical specimens in 2004 (data from a regional hospital in Hong
Kong).
Blood Respiratory specimens Urine
n=1801 n=366 n=6303 n=1669 n=9201 n=232
Organism Non- ICU rank Organism Non- ICU rank Organism Non- ICU rank
ICU/HDU (%) ICU/HDU (%) ICU/HDU (%)
rank (%) rank (%) rank (%)
E. coli 1 (24%) 2 (10%) P. aeruginosa 1 (12%) 3 (8%) E. coli 1 (40%) 2 (21%)
Coagulase-negative 2 (15%) 1 (38%) S. aureus 2 (8%) 1 (9%) Enterococci species 2 (11%) 3 (13%)
staphylococci
K. pneumoniae 3 (9%) 5 (7%) H. influenzae 3 (6%) - Klebsiella species 3 (11%) 4 (11%)
Bacillus species 4 (8%) 3 (9%) Klebsiella 4 (4%) 2 (9%) Candida species 4 (8%) 1 (32%)
species
S. aureus 5 (7%) 6 (5%) S. pneumoniae 5 (4%) - Proteus species 5 (5%) 6 (3%)
Enterococcus species 6 (3%) 4 (9%) A. baumannii 6 (4%) 6 (4%) P. aeruginosa 6 (5%) 5 (7%)
1. Patients infected with CA-MRSA do not have the usual risk factors
associated with HA-MRSA. In overseas countries, CA-MRSA were
found to be more common among certain populations: children with
chronic skin condition, prisoners, military personnel, aboriginals,
injection drug users, the homeless and contact sports athletes (13-
16); but such associations have not been observed among the CA-
MRSA cases in Hong Kong.
Vancomycin-resistant enterococci
VRE here refers to E. faecium and E. faecalis with resistance to
glycopeptides (vancomycin MIC t8 Pg/mL or teicoplanin MIC t16
Pg/mL). The incidence of VRE in Hong Kong is low at present. The first
isolate of VRE (E. faecium) in Hong Kong was imported in 1997. In the
subsequent 3 years, a few sporadic cases were identified in five
hospitals including a small cluster recently in TMH. By the end of
March 2001, about 10 cases of VRE have been detected, including
both vancomycin-resistant E. faecium (vanA and vanB) and E. faecalis
(vanA) (19). In a multicentre surveillance of 1600 consecutive patients
hospitalized in >10 ICUs in 1999, the prevalence was found to be
<0.1%.
ESBL-producing Enterobacteriaceae
1. Extended-Spectrum Beta-Lactamases (ESBLs) are any bacterial
enzymes that are capable of inactivation of third generation
cephalosporins. The term is most commonly used to refer to a
group of bacterial enzymes that are derived from the classical
beta-lactamases TEM-1, TEM-2 and SHV-1. In recent years, the
“CTX-M” type of ESBL is also emerging in several Asian countries
including China and Hong Kong SAR (20-22).
Enterobacter spp.
1. De-repression of AmpC beta-lactamase occurs most frequently
among Enterobacter spp. De-repressed mutants are resistant to
all the first, second and third generation cephalosporins.
5. Is this the right time for Hong Kong to introduce ASP? Are we
too early, or are we too late, and why?
is worse than in many other parts of the world (72). In the United
States, a “Public health action plan to combat antimicrobial
resistance-action plan” was developed in 1999. In the United
Kingdom, significant progress has been made in optimizing the
clinical use of antimicrobials since 2000 in terms of governmental
directives, strategy and action plan (67;73). Recently, similar
initiatives have been launched in Taiwan and South Korea at a
national level. It is, therefore, definitely not premature to introduce
such a “universal” and “continuous” programme to the public
hospitals in Hong Kong.
Conclusion
physicians.
diseases specialist.
Therapeutics Committee.
usage.
usage.
agents.
Reference (82)
Classification of therapy
Empirical therapy
In the clinical situation of “empirical use”, the antimicrobial(s) is/are
used as initial therapy directed to eradicate the most likely pathogens.
Before initiation of antimicrobials, appropriate specimens for stains
and culture of microorganisms should be obtained. Results of
identification and susceptibility of microorganisms are likely to be
available in the following 48 to 72 hours. The use of broad-spectrum
antibiotics or combination therapy is usually necessary to cover the
different organisms capable of causing an infection. In general, the use
of agents in this situation should not extend beyond the time required
to obtain results of cultures and susceptibility.
Choice of agent(s): based upon adequate coverage of the potential
pathogens of the potential infection sites and the anticipated
antimicrobial susceptibility patterns of the bacterial isolates.
Recommendations of empirical therapy for some common infections
are outlined in Part IV.
Known-pathogen therapy
In the clinical situation of known pathogen use, the antimicrobial(s) is
/are used when the microbiology laboratory has identified the micro-
organism causing the infection and the susceptibility pattern is
known. If during empirical use, the patient is started on combination
therapy or broad spectrum antibiotics, the antimicrobial spectrum
should be narrowed to cover the micro-organisms identified as the
aetiologic agent. Streamlining from broad-spectrum to specific, narrow
spectrum antimicrobials helps to avoid colonization with resistant
organisms and superinfections. In the absence of allergy or other
contraindications, the agent (appropriate for the site and type of
infection) with the narrowest spectrum in a group or a list of candidate
drugs should be used.
It should be noted that the skin and mucous membrane surface of the
hospitalized patient are often colonised with nosocomial bacteria (such
as MRSA, E. coli, Klebsiella spp, etc.), systemic antimicrobial therapy
(both IV and PO) should not be administered in an attempt to
eradicate these micro-organisms.
Stop therapy
x Type of infection z Education
x Clinical responses
x Follow-up culture results where
appropriate
Vancomycin
Situations in which the use of vancomycin/teicoplanin is
appropriate (6;83)
1. Treatment of serious infections caused by beta-lactam resistant
Gram-positive bacteria (e.g. MRSA, coagulase-negative
staphylococci).
2. Treatment of infections caused by Gram-positive bacteria in
patients who have serious allergies to beta-lactam antimicrobial
agents (e.g. anaphylactic reaction, Stevens-Johnson syndrome).
3. When Clostridium difficile colitis fails to respond to metronidazole
therapy or is severe and life-threatening.
4. As prophylaxis for endocarditis following certain procedures in-
patients at high risk for endocarditis; according to
recommendation from the American Heart Association. (e.g. as
prophylaxis for genitourinary or gastrointestinal procedures in
moderate or high-risk patients allergic to ampicillin/amoxicillin).
5. As prophylaxis for major surgical procedures involving the
implantation of prosthetic material or devices in known carriers
of MRSA. For elective procedures, daily washing of skin and hair
with a suitable antiseptic soap (e.g. 4% chlorhexidine liquid soap)
and topical treatment of the anterior nares with nasal mupirocin
ointment (for 5 days) are recommended before the procedures.
Vancomycin may be less effective in preventing surgical wound
infection due to methicillin-sensitive staphylococci (118).
Equations:
1. Ideal body weight (IBW)
x IBW for male = 50 kg + 0.9 kg for each cm over 152 cm (2.3 kg for each
inch over 5 feet)
x IBW for female = 45.5kg + 0.9 kg for each cm over 152 cm (2.3 kg for
each inch over 5 feet)
2. Salazar-Corcoran equation (for estimate of creatinine clearance in morbidly
obese patients):
Male patient, calculate CrCl as follows:
(137age in years) u (TBW in kg u 0.285) + (12.1 u height in meter)
0.58 u serum creatinine in Pmol/L
Registration in Yes No
Hong Kong
Formulary IV/PO. Bioavailbility of PO Only IV
linezolid is ~100%.
Usual dose IV/PO 600 mg q12h IV 7.5 mg/kg q8h (infuse over 1
h in D5)
Central venous No Yes
catheter for
administration
Effect on Nil (No effect on 1A2, 2C9, Inhibit 3A4 isoenzyme strongly,
cytochrome P450 2C19, 2D6, 2E1, 3A4) hence interactions with
midazolam, nifedipine,
astemizole, terfenadine,
cyclosporin (must monitor
level), tacrolimus
Ceftazidime
Indications for using ceftazidime (Fortum) (127)
1. Empirical therapy of neutropenic fever, either as monotherapy or
in combination with an aminoglycoside (128).
2. Therapy of infection by Burkholderia pseudomallei infection
(melioidosis).
x Probable case (compatible chest X-ray plus a melioidosis titre
of t 1/640) or definite case (isolation of B. pseudomallei).
3. Known pathogen therapy of documented infection by susceptible
Pseudomonas aeruginosaa, such as:
(a) Bacteraemia with isolation of Pseudomonas aeruginosa from
blood culture.
(b) Deep-seated infection with isolation of Pseudomonas
aeruginosa from normally sterile body site or fluid (CSF,
peritoneal fluid, pleural fluid, joint fluid, tissue, pus, etc) a.
(c) Nosocomial pneumonia, as defined by CDC guidelines
(appendix), with isolation of Pseudomonas aeruginosa in a
significant quantity, from a suitably obtained, good quality
respiratory tract specimenb.
Footnotes
a For serious P. aeruginosa infection, an anti-pseudomonal beta-lactam should be
given in combination with an aminoglycoside such as gentamicin given once daily
for the initial 3 to 5 days to achieve synergistic killing. For susceptible isolates;
anti-pseudomonal beta-lactams in decreasing order of preference: piperacillin or
piperacillin-tazobactam or ticarcillin-clavulanate > cefoperazone or cefoperazone-
sulbactam or cefepime or ceftazidime > imipenem or meropenem.
b Colonization of the respiratory tract by P. aeruginosa, especially in mechanically
ventilated patients is common. Antimicrobial therapy of colonization is not
indicated. Isolation of P. aeruginosa at the indicated quantity and specimen type is
suggestive of infection rather than colonization (in descending order of clinical
significance):
1. 102-103CFU/mL or moderate/heavy growth for protected specimen brush.
2. 103-104 CFU/mL or moderate/heavy growth for bronchoalveolar lavage.
3. Moderate/heavy growth for tracheal/endotracheal aspirate specimens with ++
to +++ white cells and absent/scanty epithelial cells.
4. Expectorated sputum (as defined by the American Society for Microbiology)
with >25 WBC/low power field and <10 epithelial cells/low power field.
Imipienem/meropenem/ertapenem
Indications for using imipenem/meropenem/ertapenem
1. Therapy of infections attributed to ESBL-producing bacteria
(such as E. coli or Klebsiella spp. ) such as:
x Bacteraemia with isolation of ESBL-producing bacteria from
blood culture.
x Deep-seated infection with isolation of ESBL-producing
bacteria from normally sterile body site or fluid (CSF,
peritoneal fluid, pleural fluid, joint fluid, tissue, pus, etc).
x Nosocomial pneumonia, as defined by CDC guidelines, with
isolation of ESBL-producing bacteria in a significant quantity,
from a suitably obtained, good quality respiratory tract
specimensa
2. Empirical therapy of neutropenic fever in high risk patients. (As
Ertapenem has no anti-pseudomonal activity, it should not be
used as empirical therapy for neutropenic fevers or for treatment
of presumed/confirmed infections by the non-fermenters such as
Pseudomonas aeruginosa and Acinetobacter.)
Footnotes
a Colonization of the respiratory tract by ESBL-producing bacteria, especially in
mechanically ventilated patients is common. Antimicrobial therapy of colonization
is not indicated. Isolation of ESBL-producing bacteria at the indicated quantity
and specimen type is suggestive of infection rather than colonization (in
descending order of clinical significance):
1. 102-103 CFU/mL or moderate/heavy growth for protected specimen brush.
2. 103-104 CFU/mL or moderate/heavy growth for bronchoalveolar lavage.
3. Moderate/heavy growth for tracheal/endotracheal aspirate specimens with
++ to +++ white cells and absent/scanty epithelial cells.
4. Expectorated sputum (as defined by the American Society for Microbiology)
with >25 WBC/low power field and <10 epithelial cells/low power field.
3. For patient with impaired renal function, give the first dose
according to body weight as above. Subsequent frequency of
administration (of the same dose) to be based on the estimated
creatinine clearance of the patient according to the following
table.
Cockcroft-Gault formula
To estimate creatinine clearance, calculate as follows
Creatine clearance for male patient (mL/min) = (140-age) x
1.2 x ideal body weight (kg) /serum creatinine (Pmol/L)
(Female: 0.85 u above value)
(Unit conversion for serum creatinine: mg/dL x 88.4 =
Pmol/L)
a
CrCl Initial dosing interval
(mL/min)
!60 q24h
40-60 q36h
20-40 q48h
<20 Follow serial levels to determine time of
next dose (level <1 Pg/mL)
a
At present, the dosage of aminoglycoside to use in a ODA strategy
has not been clearly determined. Dosages for gentamicin, tobramycin
and netilmicin have ranged from 3 to 7 mg/kg, and amikacin dosages
have ranged from 11 to 30 mg/kg. On the basis of local experiences
and a recent consensus meeting, the following doses are recommended
for initial therapy in local Chinese: for gentamicin and tobramycin, 3.5
mg/kg; netilmicin, 4.4 mg/kg and amikacin, 15 mg/kg (129).
Cryptococcus S S S S S R (MIC 32
neoformans Pg/mL)
Trichosporon S S ? I S R
Table 14. Comparison of selected pharmacokinetic parameters for the azoles and caspofungin
Fluoconazole Itraconazole Voriconazole Caspofungin
Trade name Diflucan Sporanox Vfend Cancidas
Oral >80% Capsule: 30-55% 90% Only IV
bioavailability Solution: 60-80%
Cmax 10.2 0.2-0.4 mg/L after 2-4 h of 2 mg/L after 250 oral 10 mg/L end infusion
200 mg oral
Time to Cmax 2-4 4-5 1-2 -
(hr.)
CSF 50-94% <1% 20-50% Unknown (Very low)
penetration
Plasma half-life 22-35 24-42 6-24 9-11 (terminal half-life 40-50
(hr.) hours)
Tissue Widely Levels in body fluids/CSF Widely distributed into body Widely distributed; highest
distribution distributed in low; concentrations in lung, tissues & fluid including brain concentration in liver.
most tissues liver & bone 2-3 times > & CSF
including CSF. serum. High concentration
in stratum corneum due to
drug secretion in sebum.
Principal route Renal Hepatic Hepatic Hepatic
of elimination
Active drug in 80 <1 2% 1%
urine (%)
Dosage Oral or i.v. 50- 200-400mg/day Adult, oral, 200-400 mg 12- i.v. infusion of 70 mg loading,
400 mg/day [In life-threatening hourly for 24 h, then, 100-200 then 50 mg daily
depending on situations, a loading dose mg 12-hourly;
indications should be used whether i.v. 6mg/kg 12 hourly for 24 h,
given oral capsule or IV, then 4 mg/kg 12 hourly
e.g. 200mg PO tds for first
3 days]
Renal Reduce dose; Usual dose. At CFR <10 No dose adjustment need with No dose adjustment needed. Not
insufficiency removed by ml/min, some recommend oral voriconazole. Avoid iv removed by hemodialysis
haemodialysis decrease dose 50% voriconazole in renal failure.
Hepatic - avoid ? avoid Reduce dose to 35 mg daily (after
insufficiency the 70 mg loading dose) in
moderate (Child-Pugh score 7-9).
No data on usage in patient with
severe hepatic failure
INVASIVE ASPERGILLOSIS
Voriconazole Amphotericin B (1-1.5 Efficacy of voriconazole is clear
(documented invasive mg/kg) or caspofungin for for A. fumigatus. In the case of
aspergillosis) documented non-fumigatus non-fumigatus aspergillus,
aspergillosis. treatment response requires
confirmation with a larger data
set (137).
Note: The diagnosis and treatment of systemic fungal infection is complicated. The newer anti-fungal agents (e.g.
itraconazole, voriconazole, caspofungin) should be used at the specific advice of a specialist.
Diabetic foot
infection
(a) Previously S. aureus, beta- Ampicillin- Clindamycin or [14 days]
untreated, no haemolytic sulbactam (138) or cephalexin
osteomyelitis Streptococci amoxicillin-
clavulanate
(b) Chronic, Polymicrobial: PO levofloxacin/ Ticarcillin- Cultures from ulcers
recurrent, limb aerobes + ciprofloxacin + PO clavulanate or unreliable.
threatening anaerobes clindamycin or piperacillin- Early radical debridement to
ampicillin- tazobactam obtain tissue for culture; to
sulbactam (138) exclude nercotizing fasciitis
and for cure.
Ability to insert probe to bone
suggest concomitant
osteomyelitis.
Skin and soft tissue
infections
Erysipelas or Groups A, B, C, G (IV penicillin or IV Cephalexin or
cellulitis Streptococci (r S. ampicillin or PO amoxicillin-
aureus) amoxicillin) + IV/PO clavulanate or
cloxacillin ampicillin-
sulbactam
Intra-abdominal and
GI system infections
Secondary Enterobacteriacea, Cefuroxime + (Amoxicillin- x Surgical intervention
peritonitis (PPU, B. fragilis, other metronidazole + clavulanate or essential.
other bowel anaerobes, (gentamicin or ampicillin- x BL/BLI cover anaerobes
perforation, ruptured Enterococci netilmicin) sulbactam) + including B. fragilis.
appendicitis, (gentamicin or
diverticulitis) netilmicin)
Cholangitis, Enterobacteriacea, Amoxicillin- Ticarcillin- x Adequate biliary drainage
cholecystitis or Enterococci, clavulanate or clavulanate or essential.
other biliary sepsis Bacteroides ampicillin- (cefuroxime + x BL/BLIs covermost
sulbactam (r an metronidazole) Enterobacteriaceae,
aminoglycoside) enterococci and anaerobes.
Liver abscess Enterobacteriacea, Amoxicillin- Cefuroxime + x For all cases: serology for E.
(community-acquired) Bacteroides, clavulanate or metronidazole histolytica.
enterococci, ampicillin- x CT guided or open drainage
Entamoeba sulbactam + for large abscess.
histolytica metronidazole (for E.
histolytica)
Mild to moderate Food poisoning (B. Routine antibiotic Fluid and electrolytes
gastroenteritis cereus, S. aureus, therapy not replacement.
C. perfringens), recommended
Salmonella spp.,
E. coli,
Campylobacter
spp., Aeromonas
spp.
Gynaecological
infections
Pelvic inflammatory N. gonorrhoeae, C. IV amoxicillin- IV Clindamycin Coverage of anaerobes
disease (or upper trachomatis, clavulanate or 600900 mg q8h important in tubo-ovarian
genital tract infection) Enterobacteriacea, cefoxitin 1-2 g q6h + gentamicin abscess, co-existing bacterial
(148) anaerobes + doxycycline vaginosis, HIV +ve (149).
Breast abscess Usually S. aureus IV/PO cloxacillin (+ Cefazolin or I & D essential; send pus for
(r anaerobes in PO metronidazole if amoxicillin- Gram smear and culture.
non-puerperal anaerobes likely) clavulanate or
abscess) ampicillin-
sulbactam
Head and neck
infections
Odontogenic or Oral anaerobes (IV Penicillin + PO Amoxicillin-
neck infection metronidazole) or clavulanate or
IV/PO clindamycin ampicillin-
sulbactam
Urinary tract
infections
Cystitis E. coli; S. PO Nitrofurantoin or PO Cephalexin or Encourage fluid intake
saprophyticus, b amoxicillin-
cotrimoxazole
group B clavulanate or
Streptococcus ampicillin-
sulbactamc
Acute Enterobacteriacea, IV Amoxicillin- (Ticarcillin- Blood culture and MSU
pyelonephritis Enterococcus, clavulanate or IV clavulanate or cultures, need to rule out
(Pseudomonas in ampicillin- piperacillin- obstructive uropathy.
catheter-related, sulbactam or PO/IV tazobactam if IV until afebrile 2448h, then
obstruction, fluoroquinolone suspect P. complete 14 days course with
transplant) aeruginosa) or oral drugs.
ceftriaxone 12g
q24h
Community-
acquired pneumonia
(CAP)
1. CAP, not S. pneumoniae, H. PO Amoxicillin- Meta-analysis of 127 studies
hospitalized influenzae, M. clavulanate or (n=33148): S. pneumoniae
pneumoniae, C. ampicillin- (73%); H. influenzae (14%); S.
pneumoniae, C. sulbactam r a aureus (3%); Gram-negative
psittaci (influenza macrolide rods (2%). In Hong Kong,
A, M. tuberculosis) or macrolide/azalide, tetracycline
PO amoxicillin + a or co-trimoxazole should not
newer macrolide be used alone for empiric
treatment of CAP. Locally,
5070% pen-S and pen-R S.
pneumoniae isolates (both
community and hospital
isolates) are multiply resistant
to these agents (5;155;156)
2. CAP, hospitalized As above IV/PO Amoxicillin- Cefotaxime or Modifying factors:
in general ward clavulanate or ceftriaxone r a bronchiectasis: either
(157) ampicillin- f (ticarcillin-clavulanate or
macrolides
sulbactam r a piperacillin-tazobactam or
f cefepime) + a macrolide; or
macrolides
fluoroquinolone + an
aminoglycoside
3. CAP, hospitalized As above + IV Piperacillin- Cefepime + a Ticarcillin-clavulanate and
in ICU for serious Enterobacteriaceae tazobactam or macrolide ceftazidime are not useful vs
pneumonia cefotaxime or penicillin-non-susceptible S.
ceftriaxone + a pneumoniae
macrolide
Hospital-acquired
pneumonia (HAP)
HAP, onset <4 days S. pneumoniae, H. IV/PO Ampicillin- Cefuroxime if
after admission + no influenzae, M. sulbactam or patient is
previous antibiotics catarrhalis, S. amoxicillin- penicillin-allergy
(158) aureus clavulanate (non-type I
hypersensitivity)
HAP, onset t4 days MRSA; P. IV Ticarcillin- Cefoperazone- x Refer also to guideline on
after admission + had aeruginosa, clavulanate or sulbactam or use of vancomycin.
antibiotics recently, Acinetobacter, piperacillin- cefepime r an
OR onset t5 days Klebsiella spp., tazobactam r an aminoglycoside
after admission OR Enterobacter spp. aminoglycoside
mechanical
ventilation (158)
Footnote
a
Classification and definition of group A streptococcal toxic shock syndrome (159)
Definite case = criteria IA + IIA + IIB; probable case = criteria IB + IIA + II B
Criteria IA: Isolation of group A streptococci (Streptococcus pyogenes) from a normally sterile site (e.g., blood,
cerebrospinal, pleural, or peritoneal fluid, tissue biopsy, surgical wound).
Criteria IB: Isolation of group A streptococci (Streptococcus pyogenes) from a nonsterile site (e.g., throat, sputum,
vagina, superficial skin lesion).
Criteria IIA: Hypotension, systolic blood pressure d90 mm Hg in adults or <5th percentile for age in children, and;
Criteria IIB: t2 of the following signs:
(a) Renal impairment: creatinine t177 µmol/L for adults or >2u the upper limit of normal for age. In
patients with pre-existing renal disease, a t2-fold elevation over the baseline level.
(b) Coagulopathy: platelets d100,000/mm3 or DIC defined by prolonged clotting times, low fibrinogen
level, and the presence of fibrin degradation products.
(c) Liver involvement: alanine aminotransferase (ALT), asparate aminotransferase (AST), or total bilirubin
levels >2u the upper limit of normal for age. In patients with pre-existing liver disease a t2-fold
elevation over the baseline level.
(d) Adult respiratory distress syndrome defined by acute onset of diffuse pulmonary infiltrates and
hypoxaemia in the absence of cardiac failure, or evidence of diffuse capillary leak manifested by acute
onset of generalized oedema, or pleural or peritoneal effusions with hypoalbuminaemia.
(e) A generalized erythematous macular rash that may desquamate.
(f) Soft tissue necrosis, including necrotizing fasciitis or myositis, or gangrene.
b
Avoid in patient with G6PD deficiency.
c
These agents preferred in patient with recent antimicrobial therapy.
d
Stratification schemes have been proposed to allow the physician to identify high risk patients for targeted
antimicrobial chemotherapy. One such scheme is as follows:
4. Chronic bronchial infection As for group 3 + continuous sputum Above + Enterobacteriaceae, P. aeruginosa
throughout year
e Caution required as unique groups of COPD patients appears to be the main reservoir of levofloxacin-resistant S.
pneumoniae (32). Suboptimal dose of levofloxacin has been associated with levofloxacin-resistant S. pneumoniae (32).
Ofloxacin and ciprofloxacin should not be used for treatment of pneumococcal infection. Levofloxacin is the L-isomer of
the racemate, ofloxacin. The MICs of most pneumococci in Hong Kong are close to the breakpoint of levofloxacin. In
patients with acute purulent exacerbation of chronic bronchitis, failures appeared to be common in those with
pneumococci (failures in 65%, 13/20) (16). The recommended dose for levofloxacin is 500 mg QD that for moxifloxacin is
400 mg QD. Opinion from clinical microbiologist suggested if use of fluoroquinolone is contemplated.
f
IV or PO erythromycin preferred. Alternatives for patients intolerant of erythromycin are clarithromycin and
azithromycin.
Acute pancreatitis
Severe
Mild
(Box 1 & 2)
Options
Options
1. Cefuroxime +
Carbapenem
metronidazole
2. Cefotaxime +
metronidazole
3. Piperacillin-
tazobactam
a CLSI (NCCLS) MIC (Pg/mL) breakpoints for penicillin G: sensitive, d0.06; intermediate 0.12-1;
resistant t2.
These breakpoints were decided mainly for the relevance on meningitis. For pneumococcal pneumonia,
pharmacokinetic/dynamic data indicates that isolates with MIC of up to 1ï2 Pg/mL should be
considered “sensitive” to appropriate dose of penicillin, ampicillin and amoxicillin.
x Cefazolin 100 mg
subconjunctivally at
the end of the
procedure
a
For hospitals or units with a high incidence of postoperative wound
infections by MRSA or MRSE, screening for MRSA may be indicated to
identify patients for additional preoperative measures such as
chlorhexidine bath, 2% mupirocin nasal ointment [Bactroban Nasal]
and/or the use of vancomycin as preoperative prophylaxis (see also
“Guidelines for prescribing vancomycin” section)(193).
b
For patients allergic to cefazolin or patients with high risk of MRSA /
MRSE infections, vancomycin 1 g infused over at least 1 h should be
given after premedication with an antihistamine. Rapid IV
administration may cause hypotension, which could be especially
dangerous during induction of anaesthesia.
Oral
x Neomycin and
erythromycin base
1 g each P.O. tds
the day before
operation
x Therapy should be
continued
postoperatively for
ruptured and
gangrenous
appendix
Penicillins
IV Ampicillin 0.5ï1 g q6h 8ï16
IV Cloxacillin 0.5ï1 g q6h 8ï16
IV Amoxillin-clavulanate 1.2 g q8h 85
(augmentin)
IV Ampicillin-sulbactam 1.5 g q8h 150
IV Ticarcillin-clavulanate 3.2 g q6h 208
IV Piperacillin 4 g q8h 168
IV Piperacillin-tazobactam 4.5 g q8h 324
(4.5 g q6h) (432)
Cephalosporins
IV Cefuroxime 750 mg q8h 26
IV Cefazolin 1 g q8h 39
IV Ceftriaxone 1 g q12h 62
IV Cefotaxime 1 g q8h 164
IV Cefoperazone-sulbactam 1 g q12h 179
(Sulperazon) (1 g q8h) (268)
IV Cefepime 1 g q12h 191
IV Ceftazidime 1 g q8h 239
Carbapenems
IV Meropenem 0.5 g q8h 378
(1 g q8h) (580)
IV Imipenem 500 mg q6h 458
Fluoroquinolones
IV Moxifloxacin 400 mg qd 205
PO Moxifloxacin 400 mg qd 14
Macrolides
IV Clarithromycin 500 mg q12h 100
IV Azithromycin 500 mg qd 141
Others
IV Metronidazole 500 mg q8h 14
IV Vancomycin 1 g q12h 66
IV Linezolid 600 mg q12h 800
(PO Linezolid) (600 mg q12h) (720)
IV Amphotercin B (1 50 mg qd 195
mg/kg/day) *
IV Liposomal 150 mg qd 4995
amphotericin B (3
mg/kg/day) *
IV Ampicillin 2g q4h 48
IV Penicillin G 34 MU q4h 52-69
PO Rifampin** 600 mg qd 3
Note: * Dosage for a typical body weight t70 kg and normal renal
function.
** Rifampicin should only be used in combination with another
antibiotic for meningitis by certain bacteria (e.g. multi-
resistant Streptococcus pneumoniae or MRSA) with
documented sensitivity in susceptibility testing.
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Abbreviations
Kingella
IBW Ideal body weight
IDSA Infectious Diseases Society of America
IE Infective endocarditis
IM Intramuscular
IV Intravenous
IVDA Intravenous drug abuser
KPT Known-pathogen therapy
MIC Minimal inhibitory concentration
MRPA Multiply-resistant Pseudomonas aeruginosa
MRSA Methicillin resistant Staphylococcus aureus
MSSA Methicillin sensitive Staphylococcus aureus
NCCLS National Committee for Laboratory Standards
NIH National Institues of Health
ODA Once daily aminoglycerides
PO Oral
PPU Perforated peptic ulcer
PVL Panton-Valentine leukocidin
qd Daily
qid Four times per day
syr Syrup
tab/tabs Tablet/tablets
TBW Total body weight
TDM Therapeutic drug monitoring
tds Three times per day
USS Ultrasound
VRE Vancomycin resistant Enterococcus
WHO World Health Organisation
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Part II: Antimicrobial stewardship programme 21