The Alexander Project 1998-2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents.

Abstract

The Alexander Project is a continuing surveillance study, begun in 1992, examining the susceptibility of pathogens involved in adult community-acquired respiratory tract infections (CARTI) to a range of antimicrobial agents.
This study tested the susceptibility of isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected between 1998 and 2000 to 23 antimicrobials. Minimum inhibitory concentrations of agents were determined using the broth microdilution method and interpreted according to NCCLS and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.
In total, 8882 isolates of S. pneumoniae, 8523 isolates of H. influenzae and 874 isolates of M. catarrhalis were collected during 1998-2000 from centres in 26 countries. The world-wide prevalence of penicillin resistance (penicillin MICs > or = 2 mg/l) in isolates of S. pneumoniae was 18.2% over the study period, and the prevalence of macrolide resistance (erythromycin MICs > or = 1 mg/l) in this pathogen was 24.6%. Over the study period, macrolide resistance exceeded penicillin resistance in 19 of the 26 countries included in the study. Of the non-fluoroquinolone agents, the only oral agents to which over 90% of S. pneumoniae isolates were susceptible at both NCCLS and PK/PD breakpoints were amoxicillin (95.1%) and co-amoxiclav (95.5-97.9%). The prevalence of fluoroquinolone-resistant S. pneumoniae (ofloxacin MICs > or = 8 mg/l) was 1.1%. Gemifloxacin was the most potent fluoroquinolone tested against S. pneumoniae (99.9% susceptible). In isolates of H. influenzae, beta-lactamase production was 16.9%, whereas the prevalence of beta-lactamase-negative, ampicillin-resistant strains was low (0.2%). beta-Lactamase production in M. catarrhalis world-wide remained high over the period studied (92.1%). Using PK/PD breakpoints, the most active non-fluoroquinolone agents against H. influenzae were ceftriaxone (100% susceptible), cefixime (99.8%) and co-amoxiclav (98.1-99.6%). Co-amoxiclav, cefdinir and cefixime (100%) were the most active beta-lactams against M. catarrhalis. Both H. influenzae and M. catarrhalis were highly susceptible to the fluoroquinolones.
These data demonstrate the continued evolution of and geographical variation in bacterial resistance and highlight the need for appropriate prescribing of antimicrobials in CARTI, using agents with adequate activity, based on local susceptibility profiles and PK/PD parameters.

Full text

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Journal of Antimicrobial Chemotherapy (2003) 52, 229–246
DOI: 10.1093/jac/dkg321
Advance Access publication 15 July 2003
229
...................................................................................................................................................................................................................................................................
© The British Society for Antimicrobial Chemotherapy 2003; all rights reserved.
The Alexander Project 1998–2000: susceptibility of pathogens isolated
from community-acquired respiratory tract infection to commonly used
antimicrobial agents
Michael R. Jacobs1*, David Felmingham2, Peter C. Appelbaum3, Reuben N. Grüneberg2 and the
Alexander Project Group†
1Department of Pathology, Case Western Reserve University and University Hospitals of Cleveland,
11100 Euclid Ave, Cleveland, OH 44106; 3Hershey Medical Center, Hershey, PA, USA; 2GR Micro, London, UK
Received 24 May 2002; returned 1 July 2002; revised 30 April 2003; accepted 7 May 2003
Objectives: The Alexander Project is a continuing surveillance study, begun in 1992, examining the suscep-
tibility of pathogens involved in adult community-acquired respiratory tract infections (CARTI) to a range of
antimicrobial agents.
Materials and methods: This study tested the susceptibility of isolates of Streptococcus pneumoniae,
Haemophilus influenzae and Moraxella catarrhalis collected between 1998 and 2000 to 23 antimicrobials.
Minimum inhibitory concentrations of agents were determined using the broth microdilution method and
interpreted according to NCCLS and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.
Results: In total, 8882 isolates of S. pneumoniae, 8523 isolates of H. influenzae and 874 isolates of M. catarrh-
alis were collected during 1998–2000 from centres in 26 countries. The world-wide prevalence of penicillin
resistance (penicillin MICs ≥ ≥ 2 mg/L) in isolates of S. pneumoniae was 18.2% over the study period, and the
prevalence of macrolide resistance (erythromycin MICs ≥ ≥ 1 mg/L) in this pathogen was 24.6%. Over the study
period, macrolide resistance exceeded penicillin resistance in 19 of the 26 countries included in the study. Of
the non-fluoroquinolone agents, the only oral agents to which over 90% of S. pneumoniae isolates were
susceptible at both NCCLS and PK/PD breakpoints were amoxicillin (95.1%) and co-amoxiclav (95.5–97.9%).
The prevalence of fluoroquinolone-resistant S. pneumoniae (ofloxacin MICs ≥ ≥ 8 mg/L) was 1.1%. Gemi-
floxacin was the most potent fluoroquinolone tested against S. pneumoniae (99.9% susceptible). In isolates
of H. influenzae, β β-lactamase production was 16.9%, whereas the prevalence of β β-lactamase-negative,
ampicillin-resistant strains was low (0.2%). β β-Lactamase production in M. catarrhalis world-wide remained
high over the period studied (92.1%). Using PK/PD breakpoints, the most active non-fluoroquinolone agents
against H. influenzae were ceftriaxone (100% susceptible), cefixime (99.8%) and co-amoxiclav (98.1–99.6%).
Co-amoxiclav, cefdinir and cefixime (100%) were the most active β β-lactams against M. catarrhalis. Both
H. influenzae and M. catarrhalis were highly susceptible to the fluoroquinolones.
Conclusions: These data demonstrate the continued evolution of and geographical variation in bacterial
resistance and highlight the need for appropriate prescribing of antimicrobials in CARTI, using agents with
adequate activity, based on local susceptibility profiles and PK/PD parameters.
Keywords: surveillance, antimicrobial resistance, community-acquired respiratory tract infection, Streptococcus
pneumoniae, Haemophilus influenzae, Moraxella catarrhalis
Introduction
Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
catarrhalis are the major bacterial pathogens involved in community-
acquired respiratory tract infections (CARTI).1–3 Choice of anti-
microbial therapy in CARTI is usually empirical. However, this
choice is complicated by the increasing prevalence of resistance
amongst these three major bacterial pathogens. In Haemophilus and
..................................................................................................................................................................................................................................................................
*Corresponding author. Tel: +1-216-844-3484; Fax: +1-216-844-5601; E-mail: mrj6@po.cwru.edu
†The Alexander Study group participants are listed in the Acknowledgements.
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Moraxella species, β-lactamase production is the principal resistance
mechanism to penicillins. S. pneumoniae has acquired resistance to
several classes of antimicrobial agent, including penicillins, macro-
lides, co-trimoxazole and fluoroquinolones, by a variety of mechan-
isms.4 It is, therefore, important to monitor the emergence and spread
of antimicrobial resistance both geographically and over time.
Established in 1992, the Alexander Project is a continuing surveil-
lance study examining the antimicrobial susceptibility of bacterial
CARTI pathogens to a range of compounds, with testing undertaken
in three central laboratories using standardized procedures.5 From
1992 to 1995, isolates were collected from centres in a number of
European Union countries and states in the USA. In 1996, the study
extended to centres in Mexico, Brazil, South Africa, Saudi Arabia,
Hong Kong and further European countries,6,7 with centres in Israel,
Japan, Kenya, Russia and Singapore added in 1998 and 1999. Anti-
microbial susceptibility data for 1998–2000 for the three major
CARTI pathogens are now presented.
Materials and methods
Collaborating centres
In 1998–2000, the following centres took part in the study. Africa:
Kenya, Nairobi; South Africa, Johannesburg. Eastern Europe: the Czech
Republic, Prague; Poland, Warsaw; Russia, Moscow; the Slovak Repub-
lic, Bratislava. Western Europe: Austria, Vienna; Belgium, Leuven;
France, Toulouse, Paris, Nancy, Lille, Strasbourg; Germany, Weingar-
ten, Berlin; Greece, Athens; Italy, Genoa; The Netherlands, Maastricht;
Portugal, Lisbon; the Republic of Ireland, Dublin; Spain, Barcelona;
Switzerland, Basel, Berne, Geneva, La Chaux des Fonds, Lausanne,
Lugano, Sion, St Gallen, Zurich; UK, London. Far East: Hong Kong,
Pokfulam; Japan, Tokyo, Nagasaki, Kanagawa, Sendai City; Singapore.
Middle East: Israel, Ramat-Gan; Saudi Arabia, Riyadh. Latin America:
Brazil, Sao Paulo; Mexico, Mexico City, Baja California, Monterrey,
Durango. USA: 30 centres in 23 states were included in 1998, 16 centres
in 11 states in 1999 and 23 centres in 20 states in 2000. The investigators
for each of these regions are listed in the Acknowledgements. Some
centres contributed isolates from more than one hospital and region, and
there was no restriction as to the type of hospital or laboratory that could
contribute strains.
Bacterial isolates and antimicrobial susceptibility testing
Inclusion criteria for bacterial isolates, and methods used for transport-
ation, storage and confirmation of identification of isolates, as well as
testing methods have been described in detail, previously.5–7 Briefly,
strains isolated from the sputum or blood of adult patients with CARTI
were included. Duplicate isolates from the same patient were not
accepted. Isolates were accepted from hospitalized patients only if they
were cultured from samples obtained in the first 48 h after admission.
Centres were requested to collect up to 400 isolates. After isolation, iden-
tification and susceptibility testing at the participating laboratory, stored
isolates were sent to one of three central testing centres for confirmation
of identity and standardized susceptibility testing. Susceptibility testing
was carried out by the NCCLS broth microdilution method,8 using dried
commercial plates (Sensititre, Trek Diagnostics, East Grinstead, UK)
reconstituted with Mueller–Hinton broth with 5% lysed horse blood for
S. pneumoniae and Haemophilus Test Medium for H. influenzae and
M. catarrhalis. The antimicrobials tested against S. pneumoniae included
(concentration ranges tested in mg/L): penicillin (0.015–8), amoxicillin
(0.015–16), co-amoxiclav (0.015–16), cefaclor (0.5–64), cefuroxime
(0.015–16), cefixime (0.12–16), ceftriaxone (0.015–4), cefprozil
(0.12–64), cefdinir (0.016–16), erythromycin (0.015–32), clarithromycin
(0.015–32), azithromycin (0.03–32), clindamycin (0.015–2), doxy-
cycline (0.06–8), chloramphenicol (1–16), co-trimoxazole (0.06–8, tri-
methoprim component 1:19 ratio with sulfamethoxazole), ciprofloxacin
(0.25–16), ofloxacin (0.25–16), gemifloxacin (0.004–0.5), levofloxacin
(0.12–2), gatifloxacin (0.03–1) and moxifloxacin (0.03–1). The anti-
microbials tested against H. influenzae and M. catarrhalis included
(concentration ranges tested in mg/L): ampicillin (0.12–16), amoxicillin
(0.12–16), co-amoxiclav (0.12–16), cefaclor (0.5–64), cefuroxime
(0.12–32), cefixime (0.008–16), ceftriaxone (0.004–2), cefprozil
(0.5–64), cefdinir (0.06–16), erythromycin (0.5–64), clarithromycin
(0.5–64), azithromycin (0.12–64), doxycycline (0.06–8), chloram-
phenicol (0.12–32), co-trimoxazole (0.015–4, trimethoprim component
1:19 ratio with sulfamethoxazole), ciprofloxacin (0.002–1), ofloxacin
(0.008–2), gemifloxacin (0.001–0.5), levofloxacin (0.004–0.5), gati-
floxacin (0.0002–0.5) and moxifloxacin (0.001–0.5). Breakpoint con-
centrations used to interpret MIC data qualitatively were those published
by NCCLS8 as well as pharmacokinetic/pharmacodynamic (PK/PD)
breakpoints,9–15 and are indicated in Table 1.
Quality control and quality assurance
Quality control strains recommended by the NCCLS were used on each
day of testing, and results of testing carried out were accepted if results of
control strains were within published limits. In addition, each lot of dried
panels was tested with a battery of 50 isolates of S. pneumoniae and
H. influenzae. These results were compared with those obtained with
reference frozen panels, and lots of dried trays were accepted if cumu-
lative MIC plots were comparable to those obtained in the frozen
trays. Additionally, growth properties of media used to reconstitute
microdilution trays were monitored and used only if performance was
satisfactory. β-Lactamase-negative, ampicillin-resistant (BLNAR, ampi-
cillin MIC ≥ 4 mg/L) and β-lactamase-positive, co-amoxiclav-resistant
(BLPACR, co-amoxiclav MIC ≥ 2 mg/L) isolates were retested.16
Results
Streptococcus pneumoniae
Antimicrobial susceptibility: A total of 8882 isolates of S. pneumo-
niae submitted from centres in 26 countries were tested. The anti-
microbial susceptibility of world-wide isolates of S. pneumoniae and
MIC50/90s against this pathogen are shown in Table 2. Based on
NCCLS breakpoints, the most active non-fluoroquinolone anti-
microbials against S. pneumoniae were co-amoxiclav, amoxicillin
and ceftriaxone (>95% susceptibility). Cefaclor was the least
active β-lactam with only 60.2% of isolates susceptible to this agent.
Susceptibility to erythromycin, clarithromycin and azithromycin
was similar (75.3–75.5%). Ofloxacin was the least active fluoro-
quinolone and gemifloxacin the most active in this class (92.7% and
99.9% susceptibility, respectively). Chloramphenicol was more
active than doxycycline which was more active than co-trimoxazole
(88.1%, 71.3% and 63.3% susceptibility, respectively).
Table 3 shows antimicrobial MIC50/90s from centres in each
country. There was considerable variation in MIC50/90s for all of the
β-lactams. For the macrolides, MIC90s were ≥16 mg/L in 16 of the
26 countries included. Chloramphenicol MIC90s were ≥8 mg/L for 12
countries and doxycycline MIC90s were ≥4 mg/L except for centres in
Germany, The Netherlands and the UK (≤0.5 mg/L). Co-trimoxazole
MIC90s were ≥1 mg/L in all countries. Ofloxacin MIC90s were ≤2 mg/L
in most countries, but were 4 mg/L in Italy, Spain, Japan and Israel,
and >8 mg/L in Hong Kong.
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The Alexander Project 1998–2000
231
The susceptibility of S. pneumoniae to the antimicrobials tested
for centres in each country is shown in Table 4. The prevalence of
penicillin resistance exceeded 10% in centres in 14 of the 26 coun-
tries included and was highest in Hong Kong (69.9%) and lowest in
The Netherlands and Brazil (1.1%) (Figure 1). The susceptibility of
S. pneumoniae to penicillin was ≥90% for centres in the Czech
Republic, Russia, Belgium, Germany, Italy and The Netherlands,
with Hong Kong recording the lowest susceptibility (26.4%). The
most active oral β-lactam agents overall were amoxicillin (95.1%
susceptible) and co-amoxiclav (95.5% for current formulations and
97.9% for 2000/125 mg twice daily formulation). The difference
between the coverage of the two formulations of co-amoxiclav was
particularly prominent in Hong Kong (81.9% for current formula-
tions versus 100% for 2000/125 mg twice daily formulation). The
prevalence of erythromycin resistance exceeded that of penicillin
resistance in 19 of the 26 participating countries (Table 4 and Figure 1).
The susceptibility of S. pneumoniae to erythromycin was ≥90% for
centres in Kenya, the Czech Republic, Poland, Russia, Austria,
Germany, The Netherlands and Brazil, with Hong Kong recording
the lowest susceptibility (19.7%) (Table 4 and Figure 1). Centres in
13 of the 26 countries reported S. pneumoniae susceptibilities of
≥90% for chloramphenicol, compared with only The Netherlands
and UK for doxycycline and no countries for co-trimoxazole. Sus-
ceptibility to ofloxacin was <90% in Italy, Spain Japan, Israel, and
lowest in Hong Kong (77.7%) (Table 4).
Cross-resistance and co-resistance: Overall, 11.5% of penicillin-
resistant strains were also resistant to amoxicillin, though this varied
from 0% in Belgium, the Republic of Ireland, UK, Hong Kong
and Saudi Arabia to 21.3% in the USA (Table 5). The proportion of
penicillin-resistant S. pneumoniae that were also erythromycin-
resistant varied from 7.7% in the Republic of Ireland to 97.0% in
Hong Kong and Singapore (Table 5). Cross-resistance between
Table 1. Breakpoints (mg/L) used to determine susceptible (S), intermediate (I) and resistant
(R) categories, based on PK/PD and NCCLS 2002 interpretative breakpoints8–15
NA, not applicable; AMC, co-amoxiclav; –, no breakpoint available; no NCCLS breakpoints are available for
M. catarrhalis.
aBreakpoint used to define BLNAR isolates.
bBreakpoints are expressed as amoxicillin component; testing was carried out using a 2:1 ratio of amoxicillin/
clavulanic acid.
cBreakpoint used to defined BLPACR isolates.
dBreakpoints used are for cefuroxime axetil, breakpoints for cefuroxime sodium against S. pneumoniae are
S ≤ 0.5 mg/L, I = 1 mg/L, R ≥ 2 mg/L and against H. influenzae are S ≤ 4 mg/L, I = 8 mg/L, R ≥ 16 mg/L.
eS. pneumoniae susceptibility is based on susceptibility to penicillin.
fBreakpoints used are for non-meningeal infections; breakpoints for meningitis are S ≤ 0.5 mg/L, I = 1 mg/L,
R ≥ 2 mg/L.
gBreakpoints are expressed as trimethoprim component; testing was carried out using a 1:19 ratio of
trimethoprim/sulfamethoxazole.
NCCLS breakpoints
PK/PD breakpoints
S. pneumoniaeH. influenzae
AntimicrobialSRSIRSIR
Penicillin
Ampicillin
Amoxicillin
AMC
AMC 2000/125 mg
Cefaclor
Cefuroxime axetild
Cefiximee
Ceftriaxonef
Cefprozil
Cefdinir
Erythromycin
Clarithromycin
Azithromycin
Clindamycin
Chloramphenicol
Doxycycline
Co-trimoxazoleg
Ciprofloxacin
Ofloxacin
Gemifloxacin
Levofloxacin
Gatifloxacin
Moxifloxacin
NA
NA
≤2
≤2b
≤4b
≤0.5
≤1
≤1
≤1
≤1
≤0.5
≤0.25
≤0.25
≤0.12
NA
≤4
≤0.25
≤0.5
≤1
≤2
≤0.25
≤2
≤1
≤1
NA
NA
≥4
≥4b
≥8b
≥1
≥2
≥2
≥2
≥2
≥1
≥0.5
≥0.5
≥0.25
NA
≥8
≥0.5
≥1
≥2
≥4
≥0.5
≥4
≥2
≥2
≤0.06
NA
≤2
≤2
–
≤1
≤1
–
≤1
≤2
≤0.5
≤0.25
≤0.25
≤0.5
≤0.25
≤4
–
≤0.5
–
≤2
–
≤2
≤1
≤1
0.12–1
NA
4
4
–
2
2
–
2
4
1
0.5
0.5
1
0.5
–
–
1–2
–
4
–
4
2
2
≥2
NA
≥8
≥8
–
≥4
≥4
–
≥4
≥8
≥2
≥1
≥1
≥2
≥1
≥8
–
≥4
–
≥8
–
≥8
≥4
≥4
NA
≤1
≤4
≤4
–
≤8
≤4
≤1
≤2
≤8
≤1
–
≤8
≤4
NA
≤2
–
≤0.5
≤1
≤2
–
≤2
≤1
≤1
NA
2
–
–
–
16
8
–
–
16
–
–
16
–
NA
4
–
1
–
–
–
–
–
–
NA
≥4a
≥8
≥8c
–
≥32
≥16
–
–
≥32
–
–
≥32
–
NA
≥8
–
≥4
–
–
–
–
–
–
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Table 2. Susceptibility of world-wide isolates of S. pneumoniae, H. influenzae and M. catarrhalis to 23 antimicrobials and MIC50s and MIC90s, Alexander Project 1998–2000
NA, not available; AMC, co-amoxiclav.
aFor M. catarrhalis, the percentage susceptibility to erythromycin and clarithromycin was based on the lowest concentration tested (0.5 mg/L) instead of at the breakpoints of 0.25 mg/L as MIC endpoints are
≤ 0.5 mg/L.6,7,9,22
S. pneumoniae
H. influenzae
M. catarrhalis
MIC50
MIC90
PK/PD
NCCLS
MIC50
MIC90
PK/PD
NCCLS
MIC50
MIC90
PK/PD
Antimicrobial
N
(mg/L)
(mg/L)
S (%)
S (%)
R (%)
N
(mg/L)
(mg/L)
S (%)
S (%)
R (%)
N
(mg/L)
(mg/L)
S (%)
Penicillin
8882
0.03
2
NA
68.3
18.2
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
Ampicillin
2370
0.06
4
NA
NA
NA
8523
0.25
>16
NA
81.9
17.0
874
8
16
NA
Amoxicillin
8882
0.03
2
95.1
95.1
2.1
8523
0.5
>16
81.6
83.2
16.8
874
8
16
22.7
AMC
8882
0.03
2
95.5
95.5
2.1
8523
0.5
1
98.1
99.6
0.4
874
≤0.12
0.25
100
AMC 2000/125 mg
8882
0.03
2
97.9
NA
NA
8523
0.5
1
99.6
NA
NA
874
≤0.12
0.25
100
Cefaclor
8882
1
>64
21.8
60.2
26.5
8523
4
16
1.4
89.7
3.6
874
2
4
10.9
Cefuroxime axetil
8882
0.06
8
78.6
78.6
19.7
8523
1
2
83.6
98.1
0.7
874
1
2
61.9
Cefixime
8882
0.5
>16
69.2
NA
NA
8523
0.03
0.06
99.8
99.8
NA
874
0.12
0.5
100
Ceftriaxone
8882
0.03
1
95.1
95.1
0.6
8523
≤0.004
0.008
100
100
NA
874
0.12
1
97.4
Cefprozil
8882
0.5
16
78.1
79.7
18.5
8523
2
8
22.3
92.5
2.6
874
4
8
16.0
Cefdinir
6512
0.12
8
76.5
76.5
21.9
5651
0.25
0.5
92.0
97.6
NA
421
0.25
0.5
100
Erythromycin
8882
0.06
>32
75.3
75.3
24.6
8523
4
8
<0.5
NA
NA
874
≤0.5
≤0.5
99.7a
Clarithromycin
8882
0.03
>32
75.5
75.5
24.1
8523
8
16
<0.3
79.6
0.9
874
≤0.5
≤0.5
99.9a
Azithromycin
8882
0.12
>32
74.3
75.4
24.4
8523
1
2
<1.2
99.5
NA
874
0.06
0.12
99.3
Clindamycin
8882
0.06
>2
NA
86.0
13.9
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
Chloramphenicol
8882
4
16
88.1
88.1
11.9
8523
0.5
1
98.1
97.9
1.9
874
0.5
0.5
100
Doxycycline
8882
0.12
8
71.3
NA
NA
8523
0.5
1
28.9
NA
NA
874
0.12
0.25
95.8
Co-trimoxazole
8882
0.25
8
63.3
63.3
24.8
8523
0.12
>4
78.3
78.3
17.0
874
0.25
1
72.0
Ciprofloxacin
8882
1
2
68.4
NA
NA
8523
0.015
0.03
99.9
99.9
NA
874
0.03
0.06
99.9
Ofloxacin
8882
2
2
92.7
92.7
1.1
8523
0.03
0.06
99.9
99.9
NA
874
0.12
0.12
99.8
Gemifloxacin
8882
0.015
0.03
99.9
NA
NA
8523
0.004
0.015
99.9
NA
NA
874
0.008
0.015
99.8
Levofloxacin
6512
1
1
98.9
98.9
1.1
5651
0.015
0.015
99.9
99.9
NA
421
0.03
0.06
>99.5
Gatifloxacin
3414
0.25
0.5
98.5
98.5
1.5
2764
0.008
0.015
99.9
99.9
NA
250
0.03
0.03
100
Moxifloxacin
3414
0.12
0.25
98.9
98.9
1.1
2764
0.015
0.03
99.8
99.8
NA
250
0.06
0.06
100
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Table 3. MIC50/MIC90 (mg/L) for antimicrobials tested against S. pneumoniae, Alexander Project 1998–2000
Region/country
N
Penicillin
Amoxicillin
AMC
Cefaclor
Cefuroxime axetil
Cefixime
Ceftriaxone
Cefprozil
Cefdinira
Erythromycin
Clarithromycin
Azithromycin
Clindamycin
Chloramphenicol
Doxycycline
Co-trimoxazole
Ofloxacin
Africa
540
0.12/1
0.06/1
0.06/1
1/32
0.12/4
1/8
0.06/
0.5
0.5/4
0.12/4
0.06/
0.25
0.03/ 0.06
0.06/0.25
0.06/0.12
4/4
0.12/8
1/8
2/2
Kenya
277
0.03/0.5
0.03/0.12
0.03/0.12
1/2
0.12/1
0.5/4
0.03/
0.25
0.25/ 0.5
0.12/ 0.25
0.06/ 0.06
0.03/0.03
0.06/0.12
0.06/ 0.12
2/4
0.12/8
1/8
2/2
S. Africa
263
0.25/4
0.12/2
0.12/2
2/>64
0.25/8
2/>16
0.12/1
0.5/16
0.25/8
0.06/
>32
0.03/
>32
0.12/
>32
0.06/>2
4/16
0.25/>8
2/>8
2/2
E. Europe
1109
≤0.015/
0.5
0.03/0.25
0.03/0.25
1/4
0.03/
0.5
0.25/4
0.03
/0.25
0.25/1
0.06/
0.5
0.06/0.06
0.03/0.06
0.12/ 0.12
0.06/0.12
4/16
0.12/8
0.25/4 2/2
Czech Rep.
275
≤0.015/
0.03
0.03/ 0.03
0.03/0.03
1/1
0.03/
0.06
0.25/0.5
0.03/0.03
≤0.12/
0.5
0.06/0.12
0.06/0.06
0.03/0.06
0.12/0.12
0.12/0.12
4/4
0.12/4
0.25/1 2/2
Poland
453
≤0.015/
0.25
0.03/0.12
0.03/0.12
1/2
0.03/
0.5
0.25/4
0.03/
0.12
0.25/1
0.06/4
0.06/
0.06
0.03/0.06
0.12/ 0.12
0.06/ 0.12
4/16
0.25/8
0.5/8
2/2
Russia
161
≤0.015/
0.06
0.03/0.03
0.03/ 0.03
1/1
0.03
/0.12
0.25/ 0.5
0.03/ 0.06
≤0.12/
0.25
0.06/ 0.12
0.06/ 0.06
0.03/0.06
0.12/0.12
0.06/0.12
4/4
0.12/8
0.5/2
2/2
Slovak Rep.
220
0.03/2
0.03/2
0.03/2
1/>64
0.06/8
0.5/>16
0.03/1
0.25/16
0.12/8
0.06/
>32
0.03/
>32
0.12/
>32
0.12/>2
4/16
0.25/8
0.5/>8 2/2
W. Europe
3328
≤0.015/2
0.03/2
0.03/2
1/64
0.06/8
0.25/
>16
0.03/1
0.25/8
0.12/8
0.06/
>32
0.06/
>32
0.12/
>32
0.12/>2
4/8
0.12/8
0.25/8 2/2
Austria
149
0.03/
0.12
0.03/0.06
0.03/0.06
1/2
0.06/
0.25
0.05/2
0.03/
0.12
0.5/0.5
–
0.06/0.12
0.03/0.06
0.12/0.25
0.12/0.12
4/4
0.12/4
0.25/2 2/2
Belgium
230
≤0.015/
0.06
0.03/ 0.12
0.03/0.12
1/2
0.06/
0.25
0.25/2
0.03/
0.06
≤0.12/
0.5
0.06/ 0.25
0.06/
>32
0.06/
>32
0.12/
>32
0.12/>2
4/8
0.12/8
0.25/8 2/2
France
444
0.25/4
0.12/2
0.12/2
2/>64
0.5/8
2/>16
0.12/2
0.5/16
0.5/8
>32/
>32
>32/ >32
>32/>32
2/>2
4/16
0.25/>8
0.5/>8 2/2
Germany
321
≤0.015/
0.03
0.03/0.03
0.03/0.03
1/2
0.03/
0.12
0.25/0.5
0.03/ 0.06
0.25/0.5
0.06/0.12
0.06/0.06
0.03/ 0.06
0.12/0.12
0.06/0.12
4/4
0.12/0.5 0.25/1 2/2
Greece
431
≤0.015/1
0.03/1
0.03/1
1/64
0.06/4
0.25/16
0.03/1
0.25/8
0.06/4
0.06/
>32
0.06/
>32
0.12/
>32
0.06/>2
4/8
0.25/8
0.25/4 2/2
Italy
304
≤0.015/
0.06
0.03/ 0.06
0.03/0.06
1/2
0.06/
0.5
0.25/2
0.03/
0.12
0.25/0.5
0.06/0.25
0.06/
>32
0.06/
>32
0.12/
>32
0.12/>2
4/8
0.25/>8
0.25/8 2/4
Netherlands
185
≤0.015/
0.03
0.03/ 0.03
0.03/0.03
1/1
0.03/
0.06
0.25/ 0.5
0.03/ 0.03
0.5/0.5
0.06/
0.12
0.06/0.12
0.06/ 0.06
0.12/0.12
0.12/0.12
4/4
0.12/
0.25
0.25/1 2/2

Portugal
328
≤0.015/2
0.03/2
0.03/2
1/64
0.06/4
0.25/16
0.03/1
0.25/8
0.12/8
0.06/
>32
0.03/
>32
0.12/
>32
0.12/>2
4/4
0.12/8
0.25/8 2/2
Rep. Ireland
54
≤0.015/4
0.03/2
0.03/2
1/>64
0.06/8
0.5/>16
0.03/2
0.5/16
–
0.06/16
0.03/8
0.12/16
0.12/
0.12
4/4
0.12/8
0.5/>8 2/2
Spain
295
0.03/4
0.03/2
0.03/2
1/>64
0.06/8
0.5/>16
0.03/1
0.25/16
0.12/8
0.06/
>32
0.03/
>32
0.12/
>32
0.12/>2
4/16
0.25/8
0.5/>8 2/4
Switzerland
349
0.03/0.5
0.03/
0.25
0.03/0.25
1/4
0.06/1
0.25/4
0.03/
0.25
0.25/2
0.12/4
0.06/
>32
0.03/ 32
0.12/
>32
0.12/>2
4/4
0.12/4
0.25/8 2/2
by guest on July 13, 2011
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