Non-Susceptibility Trends Among Haemophilus Influenzae And

Journal of Antimicrobial Chemotherapy (2008) 62, Suppl. 2, ii97–ii103 doi:10.1093/jac/dkn356

Non-susceptibility trends among Haemophilus inﬂuenzae and Moraxella catarrhalis from community-acquired respiratory tract infections in the UK and Ireland, 1999–2007

Ian Morrissey1*, Kirsty Maher1, Laura Williams1, Jemma Shackcloth1, David Felmingham1 Downloaded from https://academic.oup.com/jac/article/62/suppl_2/ii97/690887 by guest on 04 October 2021 and Rosy Reynolds2 on behalf of the BSAC Working Parties on Resistance Surveillance

1Quotient Bioresearch Limited, Microbiology, 7-9 William Road, London NW1 3ER, UK; 2Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK

Objectives: To determine the antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis causing community-acquired respiratory tract infections in the UK and Ireland from 1999/ 2000 to 2006/07. Methods: Sentinel laboratories across the UK and Ireland contributed up to a fixed quota of isolates of defined organisms per annum. A central laboratory confirmed the isolates’ identities, measured MICs by the BSAC agar dilution method and undertook further testing by standard methods. The variability of the MIC method was assessed by repeated annual testing of control isolates. BSAC and EUCAST breakpoints were used. Statistical analysis adjusted for inter-centre variation by random effects logistic regression. Results: A total of 7371 H. influenzae and 2529 M. catarrhalis isolates were investigated. Over 90% of the H. influenzae isolates were susceptible to most of the antimicrobials tested, the exceptions being ampicillin (84.6% susceptible), trimethoprim (84.0%), cefuroxime (82.9%), amoxicillin (77.2%) and cefaclor (11.7%). For M. catarrhalis, resistance was solely due to b-lactamase (prevalence over 91%) redu- cing susceptibility to penicillins only. There was little evidence of decreased antimicrobial susceptibility between 1999 and 2007 in either pathogen, except for a reduction in susceptibility to trimethoprim in H. influenzae (90.3% to 82.6%, P < 0.00001). On the other hand, tetracycline susceptibility in H. influenzae increased over this period in the UK and Ireland (96.5 to 98.8%, P 5 0.00008). Conclusions: Despite increased resistance in respiratory pathogens from other parts of the world, the susceptibility of H. influenzae and M. catarrhalis to all agents, except tetracycline and trimethoprim in the case of H. influenzae, has remained constant during this longitudinal study.

Keywords: resistance, surveillance, MIC, breakpoint

Introduction H. influenzae had been found in the same hospital in 1974.3 Other reports from the same period acknowledge that ampicillin Haemophilus influenzae and Moraxella catarrhalis (formerly resistance was rare in the 1970s.4 Interestingly, another study Branhamella catarrhalis or Neisseria catarrhalis)areimportant found ampicillin resistance but not tetracycline resistance in a respiratory pathogens, with the former being the more prevalent collection of 40 H. influenzae isolates from the USA around the bacterium associated with community-acquired pneumonia and same time.5 During the 1970s there was no specific surveillance acute exacerbations of chronic obstructive airways disease, whereas programme like those that exist today, and it is unclear what the latter is found most commonly in patients with sinusitis.1 sampling and testing differences there may have been between Tetracycline resistance has been documented in H. influenzae the two studies discussed above. However, at that time, efforts since the early 1970s,2 with a small collection of USA isolates were beginning to be made to standardize susceptibility methods (n ¼ 35) from 1972 showing complete resistance to this agent.3 for use when testing H. influenzae.6 In that study, no isolate was found to be ampicillin-resistant, Between the mid-1970s and early 1990s, the susceptibility of although the authors state that some ampicillin-resistant UK isolates of H. influenzae was evaluated in a more formal

...... *Corresponding author. Tel: þ44-20-7388-7320; Fax: þ44-20-7388-7324; E-mail: [email protected]

...... ii97 # The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected] Morrissey et al. way at the London Hospital, led by the late Professor across the UK and Ireland submitted up to 50 S. pneumoniae and J. D. Williams. A collection of 952 H. influenzae isolates H. influenzae and 25 M. catarrhalis each winter (October–April) from from 1977 included 1.6% that were resistant to ampicillin (all of 1999 to 2007, excluding samples taken .48 h after hospitalization. these being b-lactamase-positive) and 2.7% resistant to tetra- These isolates were re-identified using standard methods, and MICs cycline.7 Repeat surveillance in 1981 (with a larger collection of and susceptibility were determined using BSAC standard methods. 1841 isolates) indicated that resistance to ampicillin in the UK had risen almost 4-fold to 6.2%, whereas tetracycline resis- 8 tance remained fairly static at 3.1%. Unlike in 1977, some Results b-lactamase-negative ampicillin-resistant (BLNAR) isolates were found (0.9% of all isolates), BLNAR being defined as Isolate numbers and patient demographics b-lactamase non-producing strains with ampicillin MIC 4 mg/ L.8–10 In 1986, further increases in ampicillin resistance were The numbers of H. influenzae and M. catarrhalis isolates tested observed (then at 7.8%), but the rise was not as dramatic as that and source data are shown in Table 1. Each pathogen had a seen between 1977 and 1981. BLNAR accounted for 1.6% of all group of core antibiotics that were tested each year, whereas Downloaded from https://academic.oup.com/jac/article/62/suppl_2/ii97/690887 by guest on 04 October 2021 H. influenzae in 1986, almost double that for 1981.9 Tetracycline other antibiotics were either excluded or introduced in more recent years. Both pathogens were investigated for the presence resistance was 2.7% in 1986, thus with little change from 1977, 25 despite complete resistance reported from a collection of 35 iso- of b-lactamase. The total collection of isolates included 7371 lates from a USA hospital (tetracycline, MIC range 6.3– H. influenzae and 2529 M. catarrhalis. Almost the entire collec- 12.5 mg/L) in 1972.3 The final study of the London Hospital tion of isolates originated from sputum samples (.93%). series, in 1991, showed a further increase in ampicillin resist- Throughout, patient characteristics were very similar for ance, up to 14.4%. The increase in BLNAR was even greater either pathogen year on year. Most isolates were from the 60–69 with these isolates and accounted for 5.8% of all H. influenzae year and 70–79 year old age groups (Table 1), and patients with in 1991. By this time, tetracycline resistance dropped 4-fold to either pathogen were approximately evenly split between female 1.4%.10 Two other studies of susceptibility in H. influenzae in and male (Table 1). Slightly more than 50% of the isolates origi- the UK were carried out in the mid-1990s,11,12 where amoxicil- nated from hospitalized patients (collected within 48 h of admis- lin resistance was around 16%, with b-lactamase prevalence sion), with most of the remainder from General Practice hardly changed since the early 1990s. Cefaclor resistance was (Table 1). Country of origin was also very similar for both 14% and clarithromycin resistance 4% in the mid-1990s.11,12 pathogens: 61% from England, 13% from Scotland, 11% from Tetracycline susceptibility was not assessed in either of these Wales, 10% from the Republic of Ireland and 5% from Northern studies. Ireland (data not shown). This is not surprising because collec- Unlike H. influenzae, M. catarrhalis was only recognized as tion targets were based on a set number of each isolate per a bacterial pathogen, rather than a commensal, in the mid-1970s country. All these characteristics did not alter significantly from and even as recently as the late 1980s was often still referred to year to year (statistical analysis not shown), with the exception as N. catarrhalis and dismissed as clinically irrelevant.13 Studies of care setting where in the last two seasons (2005/06 and 2006/ on penicillins in the 1960s suggest that this pathogen was sus- 07) a significantly higher proportion came from General Practice ceptible to ampicillin at that time.14 The first reported (56% of both pathogens compared with 40% to 44% for the first b-lactamase-producing M. catarrhalis were found in Sweden in six seasons). 1976, at a prevalence rate of 3.8%.15 A study of 121 M. catarrhalis isolated in late 1979, also from Sweden, indicated that H. influenzae susceptibility b-lactamase prevalence had risen to 17%.16 During 1981 and 1982, the prevalence of b-lactamase in M. catarrhalis was Care setting, specimen type, age and sex had no significant around 45% in an Edinburgh hospital17 and by 1984 was at relationship with susceptibility or b-lactamase production (data nearer 70%.18 Elsewhere in the UK, b-lactamase prevalence was and statistical analysis not shown). around 50% in the mid-1980s.19 In the USA, higher rates (80 to Antibiotic non-susceptibility (intermediate and resistant cat- 90%) were reported over this period,20 –21 and similar extremely egories combined) and b-lactamase prevalence for H. influenzae high prevalence was also recorded in the UK in the early from 1999/2000 to 2006/07 are shown in Figure 1. EUCAST/ 1990s22,23 and globally by the mid- to late-1990s.12,24 Although BSAC breakpoints aim to categorize H. influenzae as intermedi- b-lactamase was not formally monitored in M. catarrhalis,itis ate to macrolides so data for erythromycin and clarithromycin clear that b-lactamase levels have increased from next to are omitted from Figure 1. Cefaclor is also omitted because per- nothing in the 1960s to almost complete carriage worldwide in centage non-susceptibility was high (at least 70% each year). the 1990s. Data for the fluoroquinolones (ciprofloxacin, levofloxacin, moxi- This paper describes susceptibility data for both pathogens floxacin and gemifloxacin) and for cefotaxime and ertapenem from the BSAC Respiratory Surveillance Programme from 1999/ are omitted because the percentage non-susceptibility was low 2000 to 2006/07. in each year (0.6% for fluoroquinolones, 1.7% for cefotaxime and 0.3% for ertapenem). No susceptibility breakpoints are published for faropenem, minocycline or tigecycline; there- Materials and methods fore, data cannot be calculated to be included in Figure 1. Summary MIC and susceptibility data for all H. influenzae iso- The methodology used is described in the survey, laboratory and stat- lates combined are shown in Table 2. Tigecycline was approxi- istical methods for the BSAC Resistance Surveillance Programmes mately one doubling dilution more active than minocycline paper in this Supplement.25,26 Briefly, approximately 20 laboratories against isolates with tetracycline MIC . 1 mg/L (data not

ii98 H. inﬂuenzae and M. catarrhalis susceptibility in the UK 1999–2007

Table 1. Sources of H. inﬂuenzae and M. catarrhalis isolates collected between October 1999 and April 2007

Patient location (%)a Sex (%) Mode of age GP hospital ,48 h institutionalc male female distributionb

H. inﬂuenzae (7371) 47.2 51.2 1.3 53.8 46.1 60–69 M. catarrhalis (2529) 45.4 52.4 1.9 50.7 49.3 70–79 aPercentages do not total 100 because of isolates with missing data. bAge bands were .5, 5–19, 20–29, 30–39, 40–49, 50–59, 60–69, 70–79 and .80 years. cInstitutional refers to prison or nursing home. Downloaded from https://academic.oup.com/jac/article/62/suppl_2/ii97/690887 by guest on 04 October 2021 35 Amoxicillin/clavulanate Ampicillin Amoxicillin Beta-lactamase Cefuroxime Tetracycline 30 Trimethoprim

15 Percent non-susceptible 10

0 1999–2000 2000–01 2001–02 2002–03 2003–04 2004–05 2005–06 2006–07

Figure 1. Change in percentage non-susceptibility for antibiotics against H. influenzae collected between 1999/2000 and 2006/07. shown). Faropenem activity was very similar to that seen with mode MICs of 0.5 and 0.25 mg/L, respectively. It is clear that amoxicillin/clavulanate (Table 2). an increase in the prevalence of isolates with amoxicillin MIC As would be expected, b-lactamase prevalence over time mir- of 2 mg/L is the cause of higher amoxicillin non-susceptibility rored ampicillin non-susceptibility, which wavered around 15% in the latter 2 years of the study (Figure 2b). A similar MIC year on year (Figure 1). Over the whole collection, 0.9% or 69 shift also occurred with ampicillin but at 1 mg/L (Figure 2a) and isolates were BLNAR according to the current BSAC definition of below the breakpoint. Therefore, amoxicillin susceptibility, but ampicillin resistance (MIC . 1 mg/L).27 Ampicillin MIC against not ampicillin susceptibility, was affected by the MIC shift. In all but four BLNAR isolates was 2 or 4 mg/L (i.e. just above the these cases, where MIC breakpoints divide the wild-type MIC breakpoint). The four isolates with higher ampicillin MIC (three distribution, it is difficult to be confident that small MIC shifts at 8 mg/L and one at 32 mg/L) were collected from three hospitals truly represent a change in susceptibility, so it is unlikely that and spread over the whole study period (data not shown). this change truly represents the development of resistance to It can be seen that amoxicillin non-susceptibility remained amoxicillin. The same argument is also true for amoxicillin/ steady at around 20 to 22% until 2003/04 before dropping to clavulanate. around 16% in 2004/05 and then increasing to around 30% in Cefuroxime non-susceptibility fluctuated between 13% and 2005/06 and 2006/07 (Figure 1). A similar pattern was also 24% over the eight seasons (Figure 1), but there was no signifi- observed with amoxicillin/clavulanate (albeit at a lower non- cant trend. Trimethoprim non-susceptibility, on the other hand, susceptibility rate). Interestingly, this trend did not occur with rose significantly from around 10% in 1999/2000 to around 17% ampicillin (Figure 1). Figure 2 shows the MIC distribution for in 2006/07 (P , 0.00001). Conversely, there was a significant both amoxicillin and ampicillin (data pre-2003 omitted for though slow downward trend (P ¼ 0.00008) in tetracycline non- clarity). It can be seen that the amoxicillin MIC distribution was susceptibility which reduced from 3.5% in 1999/2000 to 1.2% in generally one dilution higher than that for ampicillin, producing 2006/07 and dipped as low as 0.9% in 2004/05.

ii99 Morrissey et al.

Table 2. Combined summary MIC and susceptibility data for all H. inﬂuenzae collected between October 1999 and April 2007

MIC (mg/L) Percentage of isolates

Antibiotic Total no. of isolates testeda minb 50%c 90%d maxe susceptible intermediate resistant

Amoxicillin 7371 0.03 0.5 16 32 77.2 0 22.8 Amoxicillin/clavulanate 7371 0.015 0.5 1 8 92.4 0 7.6 Ampicillin 7371 0.015 0.25 8 32 84.6 0 15.4 Cefaclor 5523 0.12 4 8 256 11.7 0 88.3 Cefotaxime 7371 0.001 0.015 0.03 0.5 99.7 0 0.3 Cefuroxime 7371 0.03 0.5 2 32 82.9 11.7 5.5

Ciprofloxacin 7371 0.002 0.008 0.015 32 99.8 0 0.2 Downloaded from https://academic.oup.com/jac/article/62/suppl_2/ii97/690887 by guest on 04 October 2021 Clarithromycin 3736 0.06 4 8 128 0.8 98.3 0.9 Ertapenem 2736 0.004 0.06 0.12 1 99.9 0 0.1 Erythromycin 7371 0.06 4 8 2048 1.1 92.9 6.0 Faropenem 2810 0.03 0.5 1 16 —f —— Gemifloxacin 3736 0.001 0.004 0.015 2 100 0 0 Levofloxacin 1894 0.004 0.015 0.03 0.5 100 0 0 Minocycline 2736 0.03 0.5 1 8 — — — Moxifloxacin 4635 0.004 0.03 0.06 4 99.9 0 0.1 Tetracycline 7371 0.06 0.5 0.5 16 97.9 0 2.1 Tigecycline 2736 0.03 0.25 0.5 2 — — — Trimethoprim 7371 0.002 0.12 32 32 84.0 0 16.0 aNot all antibiotics were tested each year.25 bMin, minimum MIC. c50%, MIC where 50% of the isolates are inhibited. d90%, MIC where 90% of the isolates are inhibited. eMax, maximum MIC. f—, breakpoint not given.

M. catarrhalis susceptibility a tendency in recent years not to use older tetracyclines for the treatment of community-acquired respiratory tract infection The susceptibility of isolates collected in the 2001/02 and 2003/ (RTI) following local or national guidelines.28 04 seasons was not determined, so the data presented here do It might appear, at first glance, that cefaclor resistance has not include isolates collected during those seasons. The most increased dramatically in the UK from around 14% during distinctive, but unsurprising, feature of M. catarrhalis is pre-BSAC surveillance in the mid-1990s11,12 to over 80% in b-lactamase prevalence, which was in excess of 91% from 1999. Similarly, the pattern of clarithromycin resistance would 1999/2000 to 2006/07. No significant trend of changing suscep- appear to have altered considerably over the same period. tibility was observed for any antibiotic over time (data not However, these effects are artefacts due to the use of different shown), so only summary MIC and susceptibility data for the breakpoints. For example, cefaclor data from 1994/95 and 1995/ isolate collection as a whole are given (Table 3). It can be seen 96 were based on a resistance breakpoint of 32 mg/L.11,12 For that, as expected, the high b-lactamase prevalence produced this current study, the BSAC breakpoint of .1 mg/L was used, almost uniform resistance to ampicillin (no breakpoints are leading to a resistance rate of 88.3%.27 Re-analysis of the given for amoxicillin) and almost 80% resistance to cefaclor current data using a 32 mg/L breakpoint would estimate cefa- (Table 3). Full resistance was less common to cefuroxime clor resistance as 3.1% (data not shown), showing that, if any- (5.6%) but intermediate susceptibility was observed in almost thing, cefaclor resistance has fallen since 1996. This illustrates 30% of the isolates (Table 3). More than 99% susceptibility was that care should be taken when comparing historical data with observed for all other antibiotics (Table 3). recent studies, where breakpoints may be quite different to those used now. Similarly, current breakpoints used by other testing methods may vary compared with those used by the BSAC. Discussion Direct comparisons can, however, be made between isolates collected over the eight winter seasons during the current BSAC Susceptibility data presented here show that since 1999 ampicil- UK surveillance study. It would appear that the susceptibility of lin non-susceptibility (including BLNAR) and b-lactamase H. influenzae to antibacterial agents has hardly changed over the prevalence in H. influenzae from the UK have remained constant study period. High levels of susceptibility were seen with fluoro- at around 15%, despite a steady increase in the 1970s and quinolones, cefotaxime and ertapenem. No breakpoints were 1980s. Levels observed in 1999 were no different to those found available for faropenem, minocycline or tigecycline, but on in 1994/95 and 1995/96.11,12 Tetracycline resistance, on the MIC values alone these agents would appear to be at least other hand, has significantly reduced over time. This may reflect as active as most other agents tested. However, amoxicillin

ii100 H. inﬂuenzae and M. catarrhalis susceptibility in the UK 1999–2007

(a) 60%

2003–04 2004–05 50% 2005–06 2006–07

40%

30% Prevalence Downloaded from https://academic.oup.com/jac/article/62/suppl_2/ii97/690887 by guest on 04 October 2021 20%

10%

0% 0.015 0.03 0.06 0.12 0.25 0.5 12481632 Ampicillin MIC (mg/L)

(b) 60%

2003–04 2004–05 50% 2005–06 2006–07

40%

30% Prevalence

20%

10%

0% 0.03 0.06 0.12 0.25 0.5 12481632 Amoxicillin MIC (mg/L)

Figure 2. MIC distribution of (a) ampicillin and (b) amoxicillin against H. inﬂuenzae from 2003/04 to 2006/07. Vertical line represents breakpoint between susceptible and non-susceptible. non-susceptibility appears to have increased between 2005 and more appropriate to set amoxicillin breakpoints that match 2007 despite ampicillin non-susceptibility remaining fairly con- b-lactamase prevalence and ampicillin breakpoints. stant. This is due to a slight MIC shift that pushes amoxicillin The susceptibility of M. catarrhalis has also changed little MICs, but not ampicillin MICs, over the breakpoint. Although since 1999. It is interesting to note that, despite almost universal this shift may be very small and may simply be due to minor b-lactamase prevalence, resistance to other antibacterial agents experimental variability, it does beg the question whether has not developed in M. catarrhalis. susceptibility breakpoints should be the same for these agents Antibiotic resistance in community-acquired RTI pathogens that are similarly affected by b-lactamases but have differing in the UK and Ireland is generally perceived as being low com- MIC distributions.12 Furthermore, susceptibility reporting will pared with many other parts of the world, but this is mainly in vary from laboratory to laboratory depending on whether ampi- relation to Streptococcus pneumoniae.29 Within the European cillin or amoxicillin is used as the indicator. It would appear countries, b-lactamase prevalence in H. inﬂuenzae has been

ii101 Morrissey et al.

Table 3. Combined summary MIC and susceptibility data for all M. catarrhalis collected between October 1999 and April 2007, excluding isolates collected in 2001/02 and 2003/04

MIC (mg/L) Percentage of isolates

Antibiotic Total no. of isolates testeda minb 50%c 90%d maxe susceptible intermediate resistant

Amoxicillin 1265 0.002 16 64 512 —f —— Amoxicillin/clavulanate 2529 0.002 0.12 0.25 2 100 0 0 Ampicillin 1686 0.002 16 32 32 9.7 0 90.3 Cefaclor 1265 0.03 4 16 128 21.0 0.0 79.0 Cefotaxime 1265 0.015 0.5 1 2 — — —

Cefuroxime 2108 0.06 1 2 16 64.8 29.6 5.6 Downloaded from https://academic.oup.com/jac/article/62/suppl_2/ii97/690887 by guest on 04 October 2021 Ciprofloxacin 2529 0.008 0.03 0.06 2 99.9 0 0.1 Clarithromycin 1283 0.004 0.03 0.06 0.25 100 0 0 Ertapenem 1246 0.001 0.015 0.06 0.12 100 0 0 Erythromycin 2529 0.008 0.06 0.12 2 99.8 0 0.2 Faropenem 845 0.03 0.5 1 1 — — — Gemifloxacin 1283 0.002 0.015 0.03 0.06 100 0 0 Levofloxacin 845 0.015 0.06 0.06 1 100 0 0 Minocycline 1246 0.03 0.12 0.12 0.5 — — — Moxifloxacin 1283 0.015 0.06 0.06 0.5 100 0 0 Tetracycline 2529 0.06 0.5 1 2 99.8 0 0.2 Tigecycline 1246 0.03 0.06 0.12 0.5 — — — Trimethoprim 1686 1 16 32 64 — — — aNot all antibiotics were tested each year.25 bMin, minimum MIC. c50%, MIC where 50% of the isolates are inhibited. d90%, MIC where 90% of the isolates are inhibited. eMax, maximum MIC. f—, breakpoint not given. shown to be lower in Germany (2.0%), Italy (3.3%), The Additional information on the isolates collected in the Project is Netherlands (5.9%), Poland (5.7%), Turkey (5.0%) and Spain available on the BSAC surveillance website (www.bsacsurv.org (13.9%), but higher in France (29.1%) and Portugal (38.2%), than or through a link on the BSAC homepage www.bsac.org.uk). in the UK.30 A recent study of eastern Europe has also shown See page ii12 (Publications) for a full list of previous publi- high b-lactamase prevalence (as approximated from ampicillin cations from the Project, which may include parts of the infor- susceptibility) in Romania (31.9%).31 High b-lactamase preva- mation presented here. lence has been reported in Kuwait (26.7%), Lebanon (20.4%), Tunisia (21.1%),32 USA (27.4%),33 Thailand (48.4%)34 and South Korea (64.7%).35 Data presented here confirm that the UK and Ireland have relatively high b-lactamase prevalence in Funding H. influenzae compared with most other European countries, but higher prevalence occurs elsewhere in the world. The reason for The BSAC Respiratory Resistance Surveillance Programme country variation is unknown, but what is clear is that even 1999/2000–2006/07 has received financial support from Abbott, higher resistance rates could, at least theoretically, occur in the Aventis, Bayer, GeneSoft, GlaxoSmithKline, Merck Sharp & UK. Interestingly, it has been suggested that b-lactamase preva- Dohme, Wyeth or their predecessors. The BSAC funds the lence in H. influenzae has decreased in recent years in some work of the Resistance Surveillance Co-ordinator (R. R.) and countries.36 Future years of BSAC respiratory surveillance activity Resistance Surveillance Working Party. are planned to track any such changes in antibacterial susceptibility in the UK and Ireland. Transparency declarations Acknowledgements This article is part of a Supplement sponsored by the British Society for Antimicrobial Chemotherapy. We are grateful to all who have contributed to the success of the I. M. and D. F. have accepted grants, speaking invitations BSAC Resistance Surveillance Project, in particular the many and conference invitations from most major pharmaceutical laboratories that have collected isolates and all who have played companies in recent years. All other authors have none to a part in testing them [see page ii10 (Acknowledgements)]. declare.

ii102 H. inﬂuenzae and M. catarrhalis susceptibility in the UK 1999–2007

References 21. Alvarez S, Jones M, Holtsclaw-Berk S et al. In vitro susceptibilities and beta-lactamase production of 53 clinical isolates of 1. Pfaller MA, Ehrhardt AF, Jones RN. Frequency of pathogen Branhamella catarrhalis. Antimicrob Agents Chemother 1985; 27: occurrence and antimicrobial susceptibility among community-acquired 646–7. respiratory tract infections in the respiratory surveillance program study. 22. Powell M, McVey D, Kassim MH et al. Antimicrobial suscepti- Am J Med 2001; 111 Suppl 9A: 4S–12S. bility of Streptococcus pneumoniae, Haemophilus influenzae and 2. Anon. Chemotherapy of bronchitis. BMJ 1970; 1: 125–6. Moraxella (Branhamella) catarrhalis isolated in the UK from sputa. 3. Finland M, Garner C, Wilcox C et al. Susceptibility of pneumo- J Antimicrob Chemother 1991; 28: 249–59. cocci and Haemophilus influenzae to antibacterial agents. Antimicrob 23. Fung CP, Powell M, Seymour A et al. The antimicrobial suscepti- Agents Chemother 1976; 9: 274–87. bility of Moraxella catarrhalis isolated in England and Scotland in 1991. 4. Gordon RC, Thompson TR, Stevens LI et al. In vitro suscepti- J Antimicrob Chemother 1992; 30: 47–55. bility of Haemophilus influenzae to eight antibiotics. Antimicrob Agents 24. Doern GV, Jones RN, Pfaller MA et al. Haemophilus influenzae Chemother 1974; 6: 114–5. and Moraxella catarrhalis from patients with community-acquired res-

5. Thornsberry C, Kirven LA. Antimicrobial susceptibility of piratory tract infections: antimicrobial susceptibility patterns from the Downloaded from https://academic.oup.com/jac/article/62/suppl_2/ii97/690887 by guest on 04 October 2021 Haemophilus influenzae. Antimicrob Agents Chemother 1974; 6: SENTRY antimicrobial Surveillance Program (United States and 620–4. Canada, 1997). Antimicrob Agents Chemother 1999; 43: 385–9. 6. Jorgensen JH, Jones PM. Simplified medium for ampicillin sus- 25. Reynolds R, Hope R, Williams L et al. Survey, laboratory, and ceptibility testing of Haemophilus influenzae. Antimicrob Agents statistical methods for the BSAC Resistance Surveillance Programmes. Chemother 1975; 7: 186–90. J Antimicrob Chemother 2008; 62 Suppl 2: ii15–28. 7. Howard AJ, Hince CJ, Williams JD. Antibiotic resistance in 26. Reynolds R, Lambert P, Burton P et al. Analysis, power and Streptococcus pneumoniae and Haemophilus influenzae. BMJ 1978; 1: design of antibiotic resistance surveillance studies taking account of 1657–60. inter-centre variation and turnover. J Antimicrob Chemother 2008; 62 8. Philpott-Howard J, Williams JD. Increase in antibiotic resistance Suppl 2: ii29–39. in Haemophilus influenzae in the United Kingdom since 1977: report of 27. http://www.bsac.org.uk/susceptibility_testing/bsac_standardized_ study group. BMJ 1982; 284: 1597–9. disc_susceptibility_method.cfm (24 January 2008, date last accessed). 9. Powell M, Koutsia-Carouzou C, Voutsinas D et al. Resistance of 28. Woodhead M, Macfarlane J, BTS CAP Guidelines Committee. clinical isolates of Haemophilus influenzae in United Kingdom 1986. Local antibiotic guidelines for adult community-acquired pneumonia BMJ 1987; 295: 176–9. (CAP): a survey of UK hospital practice in 1999. J Antimicrob 10. Powell M, Fan YS, Seymour A et al. Antimicrobial resistance Chemother 2000; 46: 141–3. in Haemophilus influenzae from England and Scotland in 1991. 29. Marchese A, Schito GC. Recent findings from multinational J Antimicrob Chemother 1992; 29: 547–54. resistance surveys: are we ‘PROTEKTed’ from resistance? Int J 11. Felmingham D, Robbins MJ, Dencer C et al. Antimicrobial sus- Antimicrob Agents 2007; 29 Suppl 1: S2–S5. ceptibility of community-acquired bacterial lower respiratory tract patho- 30. Fluit AC, Florijn A, Verhoef J et al. Susceptibility of European gens. J Antimicrob Chemother 1996; 38: 747–51. b-lactamase-positive and -negative Haemophilus influenzae isolates 12. Felmingham D, Robbins MJ, Tesfaslasie Y et al. Antimicrobial from the periods 1997/1998 and 2002/3. J Antimicrob Chemother susceptibility of community-acquired lower respiratory tract bacterial 2000; 45: 191–203. pathogens isolated in the UK during the 1995–1996 cold season. J Antimicrob Chemother 1998; 41: 411–5. 31. Gracia M, Dıáz C, Coronel P et al. Antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis isolates in eight 13. Catlin BW. Branhamella catarrhalis: an organism gaining respect Central, East and Baltic European countries in 2005–06: results of the as a pathogen. Clin Microbiol Rev 1990; 3: 293–320. cefditoren Surveillance Study. J Antimicrob Chemother 2008; 61: 14. Barber M, Waterworth PM. Antibacterial activity of the penicillins. 1180–1. BMJ 1962; 1: 1159–62. 32. Alpuche C, Garau J, Lim V. Global and local variations in antimi- 15. Malmvall B-E, Brorsson J-E, Johnsson J. In vitro sensitivity to crobial susceptibilities and resistance development in the major respir- penicillin V and b-lactamase production of Branhamella catarrhalis. atory pathogens. Int J Antimicrob Agents 2007; 30S: S135–8. J Antimicrob Chemother 1977; 3: 374–5. 33. Critchley IA, Brown SD, Traczewski MM et al. National and 16. Brorson JE, Martinell J, Wilske H. Branhamella catarrhalis: anti- regional assessment of antimicrobial resistance among community- biotic susceptibility and b-lactamase production. J Antimicrob acquired respiratory tract pathogens identified in a 2005–2006 U.S. Chemother 1981; 7: 208–9. Faropenem Surveillance Study. Antimicrob Agents Chemother 2007; 17. McLeod DT, Ahmad F, Power JT et al. Bronchopulmonary infec- 51: 4382–9. tion due to Branhamella catarrhalis. BMJ 1983; 287: 1446–7. 34. Srifuengfung S, Chayakulkeeree M, Chokephaibulkit K et al. 18. McLeod DT, Ahmad F, Capewell S et al. Increase in bronchopul- Five-year study of antimicrobial susceptibility and beta-lactamase pro- monary infection due to Branhamella catarrhalis. BMJ 1986; 292: duction in Haemophilus influenzae. Southeast Asian J Trop Med Public 1103–5. Health 2007; 38: 732–6. 19. Winstanley TG, Spencer RC. Moraxella catarrhalis antibiotic 35. Hoban D, Felmingham D. The PROTEKT surveillance study: susceptibility with special reference to trimethoprim. J Antimicrob Chemother 1986; 18: 425–31. antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections. 20. Sweeney KG, Verghese A, Needham CA. In vitro susceptibilities J Antimicrob Chemother 2002; 50 Suppl 2: 49–59. of isolates from patients with Branhamella catarrhalis pneumonia compared with those of colonizing strains. Antimicrob Agents Chemother 36. Tristram S, Jacobs MR, Appelbaum PC. Antimicrobial resistance 1985; 27: 499–502. in Haemophilus influenzae. Clin Microbial Rev 2007; 20: 368–9.

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