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The New Zealand Medical Journal

 Journal of the New Zealand Medical Association, 10-October-2003, Vol 116 No 1183

Antibiotic susceptibility of Haemophilus influenzae isolates from four New Zealand sites
Haemophilus influenzae is a respiratory tract pathogen for which there are few data on the susceptibility of New Zealand isolates. Although the introduction of the serogroup b vaccine in 1994 has drastically reduced the incidence of invasive group b disease,1,2 unencapsulated strains still cause a significant number of infections, eg, otitis media, conjunctivitis. H. influenzae also causes a reasonable minority (11%) of cases of community-acquired pneumonia in New Zealand.3 National susceptibility data are limited and relate to invasive isolates.2 We therefore have determined the susceptibility profile of recently isolated non-invasive strains of H. influenzae.
Isolates were tested in four centres: three community laboratories in Christchurch, Hamilton and Auckland, and Wellington Hospital. All laboratories used the same standardised agar dilution testing protocol,4 and susceptibility interpretive standards.5 Eight antibiotics were tested in doubling dilutions from 256 μg/ml to 0.008 μg/ml. The presence of β-lactamase was tested by the nitrocefin disc method.4 Isolates were from routine clinical specimens: respiratory 39%; eye 41%; ear 12%; throat 4%; and other 4%. Repeat isolates from the same patient were excluded. Isolates were identified by routine methods (X- and V-factor testing). We aimed for 100 specimens per testing site and report the complete data on 395 isolates.

Table 1. Antibiotic susceptibility results for 395 isolates of Haemophilus influenzae

Antibiotic
MIC50
MIC90
Geometric mean MIC
Interpretive standards5
Susceptibility results (%)
S
I
R
S
I
R
Amoxicillin-clavulanate
0.5
1.0
0.45
≤4/2
-
≥8/4
99.7

0.3
Ampicillin
0.25
4.0
0.55
≤1
2
≥4
82
3
15
Cefaclor
1.0
4.0
1.61
≤8
16
≥32
97.5
2.3
0.3
Ceftriaxone
0.008
0.008
0.009
≤2
-
-
100


Ciprofloxacin
0.008
1.016
0.011
≤1
-
-
100


Clarithromycin
8.0
16.0
7.04
≤8
16
≥32
80
18
2
Co-trimoxazole
0.12
4.0
0.21
≤0.5/
9.5
1/19–
2/38
≥4/76
88
2
10
Tetracycline
0.5
0.5
0.38
≤2
4
≥8
98.2
1.3
0.5
NB: all MIC values are in μg/ml; S = susceptible; I = intermediate; R = resistant

The susceptibility results for the isolates are presented in Table 1; MIC50 and MIC90 are the concentrations inhibiting 50% and 90% of strains respectively. Most isolates, ≥97.5%, were susceptible to all the β-lactam agents tested, apart from ampicillin, as well as ciprofloxacin, and tetracycline. The proportion fully susceptible to clarithromycin, ampicillin and co-trimoxazole ranged from 80–88%. Seventy two (18%) isolates were β-lactamase positive.
There have been several large, recent studies reporting the susceptibility of H. influenzae isolates from the United States,6 Asia and Europe,7,8 and elsewhere.8 In the United States more isolates are β-lactamase positive (33%) than in New Zealand.6 In other countries there is wide variation in the proportion β-lactamase positive, eg, median 15.4% (range 5.7–32%).7 There is also wide variation in co-trimoxazole resistance, eg, median 20% (range 17–51%).7 Fewer New Zealand isolates were fully susceptible to clarithromycin (80%) than observed in other reports, eg, median 95% (range 91.3–97.4%),7 and 94.2%.6 Nevertheless, our observed rate of fully clarithromycin-susceptible isolates is close to that observed in an American study that tested almost 2000 isolates from many areas within that country, ie, 70–79% susceptible.9 Our results confirm the low rate of ciprofloxacin resistance in H. influenzae, ie, <0.5%,8 as well as essentially universal susceptibility to β-lactamase stable β-lactam agents.6–8
These results may be of interest to those developing treatment guidelines for conditions where H. influenzae may be encountered. By testing isolates from both the North and South Island and from community and hospital settings we feel the results are likely to reflect the current situation within the country. These results also serve as baseline data to allow monitoring of changes in susceptibility over time.
Arthur J Morris
Department of Microbiology, Diagnostic Medlab, Auckland
Rosemary Ikram
Medlab South, Christchurch
Mark Jones
Wellington Hospital, Wellington
Ron Leng
Pathlab, Hamilton

Acknowledgements: This study was funded by SmithKline Beecham, now trading as GlaxoSmithKline (GSK), Auckland.

References:

  1. Wilson N, Wenger J, Mansoor O, et al. The beneficial impact of Hib vaccine on disease rates in New Zealand Children. NZ Med J 2002;115(1159). URL: http://www.nzma.org.nz/journal/115-1159/122/
  2. Annual Summaries – 2002. ESR Lablink 2003;10:1–9.
  3. Neill AM, Martin IR, Weir R, et al. Community acquired pneumonia: aetiology and usefulness of severity criteria on admission. Thorac 1996;51:1010–6.
  4. National Committee for Clinical Laboratory Standards (NCCLS). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard - sixth edition. NCCLS document M7 – A6. Wayne, Pennsylvania: NCCLS; 2003.
  5. National Committee for Clinical Laboratory Standards (NCCLS). Performance standards for antimicrobial susceptibility testing. Thirteenth informational supplement. NCCLS document M100-S13(M7). Wayne, Pennsylvania: NCCLS; 2003.
  6. Thornsberry C, Jones ME, Hickey ML, et al. Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in the United States, 1997–1998. J Antimicrob Chemother 1999;44:749–59.
  7. Sahm DF, Jones ME, Hickey ML, et al. Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in Asia and Europe, 1997–1998. J Antimicrob Chemother 2000;45:457–66.
  8. Felmingham D, Gruneberg RN. The Alexander Project 1996–1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections. J Antimicrob Chemother 2000;45:191–203.
  9. Hogan PA, Sheehan DJ. Macrolide susceptibility and beta-lactamase production among haemophilus influenzae isolates in the United States, 1996–1997. Antimicrob Agents Chemother 1998;42:3313–4.


     
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