Ogni antibiotico è efficace in relazione a un determinato gruppo di microrganismi comprare keflex senza ricettain caso di infezioni oculari vengono scelte gocce ed unguenti.

Antibiotic resistance among bacterial pathogens in central africa: a review of the published literature between 1955 and 2008



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International Journal of Antimicrobial Agents xxx (2009) xxx–xxx Contents lists available at International Journal of Antimicrobial Agents Antibiotic resistance among bacterial pathogens in Central Africa: a reviewof the published literature between 1955 and 2008 E. Vlieghe , M.F. Phoba , J.J. Muyembe Tamfun , J. Jacobs a Department of Clinical Sciences, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgiumb Institut National de Recherche Biomédicale (INRB), Avenue de la Démocratie (ex Huileries), Kinshasa/Gombe B.P. 1197 Kinshasa 1, Democratic Republic of the Congo Article history: A systematic review of the published literature on bacterial resistance in Central Africa between 1955 Received 2 February 2009 and 2008 was performed. Eighty-three publications from seven countries were retrieved, the majority Accepted 30 April 2009 presenting data on enteric and other Gram-negative pathogens. Despite methodological limitations inmany studies, alarming resistance rates are noted in nearly all pathogens. Of special concern are mul- tidrug resistance in Shigella and Salmonella spp. and the emergence of meticillin-resistant Staphylococcus aureus, high-level penicillin-resistant Streptococcus pneumoniae and extended-spectrum ␤-lactamases Antibacterial agents among Gram-negative pathogens. These findings make clear that the Central African region shares the worldwide trend of increasing antimicrobial resistance and is in urgent need of sound surveillance based Surveillance review on competent and affordable microbiology to provide clear data on antimicrobial resistance. These datacould enable redaction of local treatment guidelines and fuel national and regional policies to containantimicrobial resistance.
2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
tuberculosis and agents causing sexually transmitted infections.
Relevant literature was identified from the PubMed online database Developing countries face substantial problems of antimicrobial of the US National Library of Medicine. Search terms included ‘bac- resistance. Contributing factors include those involving the public terial resistance', ‘antibiotic use', ‘antimicrobial resistance' and (e.g. self-medication), prescriber (e.g. misinformation, absence of ‘bacterial surveillance' combined with the different countries diagnostic tools) and dispenser (e.g. over-the-counter use, inad- and ‘Central Africa'. Bibliographies of all relevant papers were equate storage, use of expired drugs) ect knowledge of searched to identify further papers. A similar search was also actual resistance patterns is the cornerstone of successful contain- performed in the Medical Literature on Central Africa database at ment of antimicrobial resistance. Good-quality data are available the library of the Institute of Tropical Medicine Antwerp (Belgium).
from more affluent and transitory countries (e.g. in Latin America In addition, relevant websites providing medical literature for use Asia but there is little information available from in developing countries were accessed.
many countries in sub-Saharan Africa, especially from the Central All articles were reviewed by at least two authors. Only publi- African region. Thus, a systematic review was performed to compile cations listing original data on bacterial resistance in humans were the available information on bacterial resistance in this region.
included. Studies were further assessed for design, setting, demo-graphic data and microbiological methodology. Studies reporting 2. Materials and methods
archived results of susceptibility testing as part of routine clini-cal care were categorised as retrospective laboratory studies, and The region of Central Africa was considered as described in studies addressing a particular clinical condition (e.g. meningitis) the United Nation's geoscheme comprising the countries were termed clinical studies. Surveillance studies were considered Cameroon, Chad, Gabon, São Tomé e Príncipe, Congo-Brazzaville, as those complying with the World Health Organization (WHO) Democratic Republic of the Congo (DRC) (formerly Zaire), the surveillance standards i.e. studies focusing on a particular Central African Republic (CAR), Angola and Equatorial Guinea. The pathogen carried out by a reference laboratory and/or a network study focused on bacterial pathogens, excluding Mycobacterium of sentinel laboratories.
The WHO criterion of 48 h hospital admission was used for the distinction between community- and hospital-acquired (nosoco- ∗ Corresponding author. Tel.: +32 3 821 39 77/47 582 15 83.
mial) infections. If no data on duration of hospital admission were E-mail address: (E. Vlieghe).
mentioned, the categories as mentioned by the authors were used.
0924-8579/$ – see front matter 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Please cite this article in press as: Vlieghe E, et al. Antibiotic resistance among bacterial pathogens in Central Africa: a review of thepublished literature between 1955 and 2008. Int J Antimicrob Agents (2009), doi: ARTICLE IN PRESS
E. Vlieghe et al. / International Journal of Antimicrobial Agents xxx (2009) xxx–xxx Relevant microorganisms and antibiotics were primarily those external quality programmes were mentioned in only 14 and 3 listed by the WHO Surveillance Standards. Key organisms included studies, respectively. Only 5 (6.0%) of 83 studies considered only Staphylococcus aureus, Streptococcus pneumoniae, the enteric one sample per patient and per episode as recommended pathogens (i.e. Campylobacter, Vibrio, Shigella and Salmonellaspp.), Klebsiella pneumoniae, Escherichia coli, Pseudomonas aerugi- 4. Resistance rates for different species
nosa, Haemophilus influenzae and Neisseria meningitidis. Antibioticsincluded the first-line antibiotics [benzyl penicillin, ampi- 4.1. Gram-positive bacteria cillin and/or amoxicillin, oxacillin, trimethoprim/sulfamethoxazole(SXT), tetracycline, chloramphenicol, erythromycin, clindamycin 4.1.1. Staphylococcus aureus and nalidixic acid] as well as representatives of the different gen- Resistance data for S. aureus were reported in nine studies, erations of cephalosporins, aminoglycosides and fluoroquinolones.
including three surveillance studies and six clinical studies from Unless otherwise stated, intermediate-resistant strains were urban hospitals. Although a wide range of samples (pus, wounds, grouped together with resistant strains. Mean resistance rates for urine and CSF) was addressed from mixed origins (community, data from different studies combined were calculated by dividing nosocomial), only one study considered blood cultures f note the sum of all resistant organisms (nominator) over the sum of all is that in some studies panels for susceptibility testing were not in organisms tested (denominator). The minimum number of isolates accordance with WHO surveillance standards, e.g. did not contain per species for separate reporting was set at 10, in line with the oxacillin or an equivalent antibiotic European Society of Clinical Microbiology and Infectious Diseases As can be seen in the presence of meticillin-resistant Study Group for Antimicrobial Resistance Surveillance (ESGARS) S. aureus (MRSA) was examined in six studies. Kesah et al. the Clinical and Laboratory Standards Institute (CLSI) surveyed MRSA prevalence in eight African countries, including Cameroon as the only country from Central Africa. They foundMRSA in 27 (21.3%) of 127 Cameronese samples. This was amongthe top three highest prevalence figures in the study, only after 3. Results
Kenya (38/137; 27.7%) and Nigeria (42/142; 29.6%). A recent Con-golese study nasal staphylococcal carriers reported an 3.1. Overview of study design, study setting and microbiological MRSA prevalence of 63.1%, 66.7% and 23.3% in hospitalised patients, hospital staff and outpatients, respectively.
A total of 173 articles published between 1954 and 2008 were 4.1.2. Streptococcus pneumoniae retrieved, of which 83 were eligible for inclusion in the review.
Data were found in 11 studies conducted between 1990 The majority of these publications originated from DRC (n = 37, and 2008, mainly in urban children. Clinical samples were pre- including 3 publications on data from Rwandese and Congolese dominantly from CSF (8/11; 72.7%); one study described blood patients during cross-border epidemics), followed by CAR (n = 15) culture isolates Another two studies described surveil- and Cameroon (n = 14) (More than one-half (43/83; 51.8%) of lance in nasopharyngeal isolates from healthy and sick children the studies were surveillance studies, the majority of them study- ing enteric pathogens (30/43; 69.8%) in DRC (21/43; 48.8%). Another Overall, low numbers of isolates were studied (range 7–272; large part of the studies (34/83; 41.0%) were retrospective labora- median 34); only 4/11 studies tested more than 50 isolates. Peni- tory studies or short-term clinical studies.
cillin was tested in eight studies, of which only four distinguished Most studies (50/83; 60.2%) were carried out in urban settings.
between ‘intermediate' and ‘high-level' resistance. Although rates Of the rural studies, nearly three-quarters (18/25; 72.0%) were per- of intermediate resistance to penicillin were reported up to 67.0%, formed in DCR, mainly on Shigella spp. and other enteric pathogens.
high-level resistance remained <6% overall. Notable resistance The median duration of studies was 16.5 months (range 1–133 rates were those for SXT (up to 69%) and chloramphenicol (up to Among the studies that mentioned the patients' age groups, there was a predominance of studies on or involving children 4.2. Gram-negative bacteria (40/50; 80.0%). The origin of infection was clearly retrievable in56 studies, most of which (52/56; 92.9%) described community- 4.2.1. Shigella spp. acquired infections, and only 4 studies explicitly addressed Eighteen studies were found, mainly from rural DRC (12/18; nosocomial infections was stated in only five 66.7%) and published between 1955 and 2006. Two-thirds reported studies, mainly human immunodeficiency virus (HIV) and sickle on outbreak investigations, and Shigella dysenteriae type 1 was the predominant serotype (15/18 studies). Occasionally, samples from A research or reference laboratory was involved in 58 (69.9%) of blood, CSF or pus were included ultiresistant Shigella iso- the 83 studies, the vast majority of which addressed Vibrio cholerae lates emerged in the late 1970s. A survey from Kinshasa (DRC) in and Shigella spp. Faeces were the most frequently studied clini- 1964 demonstrated resistance to two or more antibiotics in 10% of cal sample (42/83; 50.6%), followed by blood (19/83; 22.9%) and 368 strains. In 1979, spread of a clone with plasmid-mediated resis- cerebrospinal fluid (CSF) (18/83; 21.7%).
tance to ampicillin, chloramphenicol, streptomycin, sulphonamides The methodologies of antibiotic susceptibility testing were and tetracycline was noted in Eastern Zaire (now DRC) described in 71 studies (85.5%), including mainly the disk diffusion and 2 years later 75% of the strains showed additional trimethoprim method (60/83; 72.3%) and the agar dilution method (17/83; resistance through a newly acquired plasmid. Dysentery treat- 20.5%). Broth dilution and Etest were performed in four and three ment consequently shifted to nalidixic acid, to which resistance studies, respectively. Batch testing with the agar dilution method developed in May 1982, disappearing after the discontinuation of was mainly used by reference laboratories assessing outbreaks of V. mass treatment with nalidixic acid everal reports described cholerae and Shigella spp. Only 31 (37.3%) of 83 studies mentioned the large outbreak of S. dysenteriae dysentery among Rwandese a reference method such as the Kirby–Bauer method (or its mod- refugees after the 1994 civil war reporting simi- ifications) or the methods of the CLSI the French Society lar patterns of multidrug resistance including nalidixic acid and for Microbiology Use of control stains and participation in trimethoprim, leaving the newer fluoroquinolones as a treatment Please cite this article in press as: Vlieghe E, et al. Antibiotic resistance among bacterial pathogens in Central Africa: a review of thepublished literature between 1955 and 2008. Int J Antimicrob Agents (2009),


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E. Vlieghe et al. / International Journal of Antimicrobial Agents xxx (2009) xxx–xxx Fig. 1. Map of the Central African region, with numbers of articles retrieved per country. DRC, Democratic Republic of the Congo; CAR, Central African Republic.
option. Bercion et al. Cunin et al. ed similar 4.2.2. Salmonella spp. outbreaks in CAR and Cameroon, respectively. Even outside the epi- demic context, the prevalence of multidrug-resistant strains was (Thirteen studies between 1973 and 2005 addressed found to be >50% in recent reports from Kinshasa (DRC) S. Typhi, mainly in urban settings in DRC and Gabon (10/13; 76.9%). Six of them were surveillance studies f Table 1
Antimicrobial resistance rates of Staphylococcus aureus, Central Africa
Antimicrobial agent Resistance rate (%) as reported in different studies Mean resistance rate (%) Penicillin (or ampicillin, amoxicillin) 0.0 (2 studies), 53.6, 68.0, 62.8, 82.9, 89.5 0.0 (2 studies), 5.3, 21.3, 35.7, 63.1 0.0 (2 studies), 2.8, 33.3, 75.0 0.0 (2 studies), 5.4, 10.0 0.0 (2 studies), 1.4, 5.3 a Countries and years of publication: Democratic Republic of the Congo (1954, 2001, 2004, 2004), Cameroon (1990, 2003), Congo Brazzaville (2006), Gabon (1985) and Central African Republic (2007).
b Number of resistant strains/total number of strains in each study, expressed as %.
c Sum of all resistant organisms/sum of all organisms tested.
Table 2
Antimicrobial resistance rates of Streptococcus pneumoniae, Central Africa
Antimicrobial agent Resistance rate (%) as reported in different studies Mean resistance rate (%) Penicillin (intermediate resistance) 8.8, 6.0, 28.6, 29.6, 67.0 Penicillin (high-level resistance) 0.0 (2 studies), 4.2, 5.6 (2 studies), 5.7 0.0 (2 studies), 1.4 14.3, 32.4, 36.0, 62.0 0.0, 6.2, 61.1, 69.0 4.0, 5.5, 9.2, 11.1, 20.7, 25.0, 25.9, 43.5, 44.0, 60.6 a Countries and years of publication: Democratic Republic of the Congo (2005), Cameroon (1990, 1991, 2001), Gabon (2002, 2004) and Central African Republic (1997, 2000, 2003, 2006, 2008).
b Number of resistant strains/total number of strains in each study, expressed as %.
c Sum of all resistant organisms/sum of all organisms tested.
d No clear specification of intermediate or resistant by author ed intermediate resistance.
Please cite this article in press as: Vlieghe E, et al. Antibiotic resistance among bacterial pathogens in Central Africa: a review of thepublished literature between 1955 and 2008. Int J Antimicrob Agents (2009), doi: ARTICLE IN PRESS
E. Vlieghe et al. / International Journal of Antimicrobial Agents xxx (2009) xxx–xxx Table 3
Antimicrobial resistance rates of Salmonella enterica serovar Typhi, Central Africa
Antimicrobial agent Resistance rate (%) as reported in different studies Mean resistance rate (%) Ampicillin and amoxicillin 0.0 (5 studies), 5.5, 21.0, 55.5 0.0 (4 studies), 4.0, 23.5, 28.0, 41.0, 50, 66.6 0.0 (3 studies), 8.0 (2 studies), 37.5 Fluoroquinolones (ofloxacin, ciprofloxacin) 0.0 (3 studies), 98.4 0.0 (5 studies), 44.4 First-generation (cefalothin, cefazolin) Second-generation (cefamandole, cefoxitin) Third-generation (cefotaxime, ceftriaxone) ND, no data.
a Countries and years of publication: Democratic Republic of the Congo (1973, 1977, 1984, 1991, 1999, 2005); Gabon (1997, 1999, 2000, 2001); Central African Republic (1978, 1984) and Cameroon (2001).
b Number of resistant strains/total number of strains in each study, expressed as %.
c Sum of all resistant organisms/sum of all organisms tested.
which five were conducted in DRC. Isolates were recovered from noted to cefotaxime. Unlike S .Typhi, there was no clear temporal blood and faeces. Although mean resistance rates to amoxicillin, trend, except for SXT and the fluoroquinolones to which resistance chloramphenicol and SXT were relatively low, there was a steeply emerged from 1999 onwards.
increasing upward trend towards 50% resistance rates since the Multiresistance was reported frequently. In a 1973 study of a mid 1990s. Overall susceptibility for fluoroquinolones remained hospital outbreak in DRC, Kashemwa et al. ted 24% of all NTS high. Only a single study ested resistance for nalidixic acid isolates to have combined resistance to ampicillin, streptomycin, as a predictor for fluoroquinolone resistance: all 37 samples were kanamycin, tetracycline, chloramphenicol and sulfamethoxazole.
sensitive. Combined resistance was described in at least three Also in DRC, in 1977 Muyembe et al. ed multiresistance studies. In a paediatric bacteraemia study in the DRC, Kariuki et al.
in 76% of 1070 NTS isolates, of which >90% were co-resistant to resistance to five or more first-line antibiotics in >95% at least five commonly used antibiotics. In a 1993 Congolese bac- of the isolates.
teraemia study, multiresistance was noted in 30% of all NTS; 90%of isolates were co-resistant to ampicillin, chloramphenicol, tetra- 4.2.2.2. Non-typhoid Salmonella (NTS) cycline, streptomycin, sulphonamides, streptomycin and SXT (The general study characteristics were similar to those Similar findings were described in Bangui (CAR) reporting on S. Typhi, with five studies also addressing nosocomialinfections. High mean resistance rates were noted for ampicillin 4.2.3. Vibrio cholerae (63.0%), chloramphenicol (42.9%) and the fluoroquinolones (16.8%).
Eleven reports from nearly all countries in the region were avail- Resistance to SXT was relatively low (14.6%) and no resistance was able. Most were published in the second half of the 1990s, often Table 4
Antimicrobial resistance rates of non-typhoid Salmonella spp., Central Africa
Antimicrobial agent Resistance rate (%) as reported in different studies Mean resistance rate (%) Ampicillin and amoxicillin 5.4, 62.9, 69.0, 92.7, 100 (3 studies) 5.7, 31.3, 35.4, 54.3, 67, 75, 100 (2 studies) 0.0, 1.1, 7.0, 16.0, 42.9, 53.9, 100 Fluoroquinolones (ofloxacin, ciprofloxacin) 0.0 (2 studies), 1.6, 85.7 0.0 (3 studies), 15.0 First-generation (cefalothin, cefazolin) Third-generation (cefotaxime, ceftriaxone) ND, no data.
a Countries and years of publication: Democratic Republic of the Congo (1973, 1977, 1984, 1984, 1991, 2001, 2004, 2005), Central African Republic (1984, 1990, 2008), Gabon (1986) and Cameroon (2001).
b Number of resistant strains/total number of strains in each study, expressed as %.
c Sum of all resistant organisms/sum of all organisms tested.
Please cite this article in press as: Vlieghe E, et al. Antibiotic resistance among bacterial pathogens in Central Africa: a review of thepublished literature between 1955 and 2008. Int J Antimicrob Agents (2009), ARTICLE IN PRESS
E. Vlieghe et al. / International Journal of Antimicrobial Agents xxx (2009) xxx–xxx Table 5
Antimicrobial resistance rates of Escherichia coli, Central Africa
Antimicrobial agent Resistance rate (%) as reported in different studies Mean resistance rate (%) Ampicillin and amoxicillin Median 82.1 (range 64.0–100) in 12 studies 2184/2834 (77.1%) Median 64.5 (range 15.0–100) in 7 studies 1753/2363 (74.2%) Nitrofurantoin (urinary tract isolates) Trimethoprim (urinary tract isolates) Median 63.3 (range 0.0–87.1) in 11 studies 1264/1839 (68.7%) Fluoroquinolones (ofloxacin, ciprofloxacin) 0.0 (2 studies), 9.0, 10.0, 43.5 0.0 (2 studies), 6.0, 11.2, 16.0, 20.0, 21.0, 91.1 First-generation (cefalothin, cefazolin) Second-generation (cefamandole, cefoxitin) Third-generation (cefotaxime, ceftriaxone) 0.0 (4 studies), 9.0 a Countries and years of publication: Democratic Republic of the Congo (1958, 1976, 1979, 1990, 1998, 2001, 2004, 2005), Cameroon (1999, 2006), Angola (1992), Gabon (1985, 2003) and Central African Republic (2003).
b Number of resistant strains/total number of strains in each study, expressed as %.
c Sum of all resistant organisms/sum of all organisms tested.
describing outbreaks among refugees, all by V. cholerae O1 El Tor.
resistance rates were noted for amoxicillin/clavulanic acid (52.9%), Three studies from Chad, Cameroon and DRC noted little or no resis- chloramphenicol (43.2%), gentamicin (47.7%) and SXT (80.3%). For tance owever, extensive and multidrug resistance was fluoroquinolones and third-generation cephalosporins, resistance described from outbreaks in DRC (1995–1997) with strains resistant is emerging (7.4% and 3.3%, respectively). Susceptibility to car- to first-line drugs including ampicillin, tetracycline, doxycycline, bapenems remained preserved. Ndip et al. (Cameroon) SXT, nalidixic acid and chloramphenicol. In the same period, sim- Burchard and Wolff (Gabon) ed multiresistance for ilar findings were reported from neighbouring Angola (combinations of) ampicillin, doxycycline, SXT and chlorampheni- Of nine studies testing ampicillin, seven showed high (≥84%) rates col at 77.3% and 33%, respectively.
of resistance. For tetracycline and chloramphenicol, four of eightstudies revealed very high (>90%) resistance rates. Isolates were 4.2.6. Presence of extended-spectrum ˇ-lactamase (ESBL) resistant to sulphonamides or SXT in six and five of eight studies, Two authors focused on the presence of ESBLs in Gram-negative bacteria Both used the double-disk method and stud-ied miscellaneous Enterobacteriaceae, mostly E. coli and Klebsiella 4.2.4. Escherichia coli spp. Frank et al. in Bangui (CAR) ed an ESBL prevalence Most data on E. coli were retrieved from clinical or labora- of 4% among 450 Enterobacteriaceae isolates. In addition, nearly tory archives, predominantly from urine and faeces, and rarely 65% of the ESBL-producing isolates showed combined resistance to from blood or pus. Two publications focused on enteroaggrega- aminoglycosides, tetracycline and fluoroquinolones. In Cameroon, tive E. coli in children and Cunin et al. ed a Gangoué-Pieboji et al. ed the presence of ESBL in 13 dysentery outbreak with E. coli 0157 in Cameroon. Overall, broad (14.3%) of 91 E. coli isolates and in 12 (18.8%) of 64 Klebsiella spp. ranges of antibiotics were used for susceptibility testing and several tested. A large part (47–84%) of these isolates was of nosocomial inappropriate drugs (e.g. clindamycin, erythromycin, tetracycline origin. Most of them carried CTX-M-15 and SVH-12 and to a lesser and doxycycline) were tested The reported and mean extent CTX-M-3 and SHV 2a as the responsible gene.
resistance rates were very high for all commonly used antibi-otics but also for amoxicillin/clavulanic acid and first-generation 4.2.7. Pseudomonas aeruginosa ( cephalosporins. Resistance remained much lower for aminoglyco- Four studies described resistance data from urine, pus and res- sides, fluoroquinolones and nitrofurantoin, and no resistance to piratory tract samples and the hospital environment; they included third-generation cephalosporins was reported by the cited authors few invasive (blood) samples. At least one study included nosoco- with the exception of Gangoue-Pieboji et al. on multire- mial samples esistance was not limited to gentamicin and sistance were recorded from DRC and Gabon by Jalaluddin et al. piperacillin but also extended to fluoroquinolones and ceftazidime and Burchard and Wolff espectively. The former described 10 (15.5% and 32.2% mean resistance rates, respectively). Resistance to different resistance patterns, with the most frequent pattern being carbapenems was looked for in a single study and remained low combined resistance to tetracycline, ampicillin, chloramphenicol, streptomycin and chloramphenicol. Similarly, 26.7% of 86 isolates in Multiresistance to clinically relevant antibiotics was assessed by the latter study combined resistance to ampicillin with doxycycline, Ndip et al. in Cameroon noted combined resistance to at SXT and chloramphenicol.
least two antibiotics in all strains. Multidrug resistance to at leastfour antibiotics was as frequent as 41.2%.
4.2.5. Klebsiella spp. Eleven authors described resistance patterns in Klebsiella spp.
4.3. Gram-negative cocci from a variety of samples (blood, urine, respiratory, pus and fae-ces). Similar to E. coli, the source of information was archived 4.3.1. Neisseria meningitidis clinical or laboratory data in large urban centres from a hetero- Data between 1968 and 2008 were found, mainly from coun- geneous group of patients, covering the period 1976–2006. High tries near to the meningitis belt (i.e. Chad, Cameroon). Unlike most Please cite this article in press as: Vlieghe E, et al. Antibiotic resistance among bacterial pathogens in Central Africa: a review of thepublished literature between 1955 and 2008. Int J Antimicrob Agents (2009), doi: ARTICLE IN PRESS
E. Vlieghe et al. / International Journal of Antimicrobial Agents xxx (2009) xxx–xxx Table 6
Antimicrobial resistance rates of Klebsiella spp., Central Africa
Antimicrobial agent Resistance rate (%) as reported in different studies Mean resistance rate (%) Ampicillin and amoxicillin Median 97.6 (range 6.0–100) in 10 studies Median 42.6 (range 25.0–95.7) in 6 studies Median 84.2 (range 12.7–100) in 10 studies 1159/1444 (80.3%) 0.0, 2.0, 4.5, 42.9 Median 43.0 (4.8–94.4) in 7 studies First-generation (cefalexin, cefazolin) Second-generation (cefoxitin, cefuroxime) a Countries and years of publication: Democratic Republic of the Congo (1976, 1979, 1990, 2001, 2004, 2005), Cameroon (2001, 2006), Angola (1992) and Gabon (1985, 2004).
b Number of resistant strains/total number of strains in each study, expressed as %.
c Sum of all resistant organisms/sum of all organisms tested.
Cameroon were most represented; for Equatorial Guinea and São Tomé e Príncipe, no usable data were found. Second, at present we did not consider agents of mycobacterial and sexually transmitted Antimicrobial agent Resistance rate (%) as reported in different studies Regarding the retrieved studies, several issues regarding epi- demiological and microbiological methods must be mentioned.
First, it should be noted that few studies were designed as prospec- tive surveillance studies. Furthermore, many studies performed 43.4, 51.0, 66.7, 93.0 susceptibility testing on only a fraction of isolates recovered, and few studies mentioned selection of a single strain per patient and episode. Enteric pathogens (Shigella, Salmonella, Vibrio spp.) were far more represented than the other key pathogens. Only a few reports essed genuine nosocomial and/or invasive iso- lates, which are notorious for their antimicrobial resistance even a Countries and years of publication: Democratic Republic of the Congo (2003), in developing countries n the other hand, urine, respiratory Cameroon (2005, 2006) and Gabon (1985).
and wound samples from clinical studies might include a selec- Number of resistant strains/total number of strains in each study, expressed as tion of difficult-to-treat infections and hence possibly present a c Sum of all resistant organisms/sum of all organisms tested.
bias toward resistant strains ith regard to microbiologicalmethods, few studies mentioned application of quality assurancein identification and susceptibility testing, and quantitative suscep- other pathogens studied, resistance to all commonly used antibi- tibility data (e.g. MICs or inhibition diameters) were only rarely otics was not demonstrated or was very low, although minimal available. Likewise, distinction between intermediate and high- inhibitory concentration (MIC) values were not reported and num- level resistance in case of S. pneumoniae was not always reported, bers studied were low. Most authors reported resistance data for and in several studies panels of antibiotics selected for testing were penicillin [mean resistance rate 1/76 (1.3%)] and chloramphenicol heterogeneous (making comparisons difficult) or even inappropri- [mean resistance rate 2/91 (2.2%)]. Some authors gave also resis- tance figures for rifampicin (no resistance noted in seven isolates Despite the limitations, several interesting observations can be tested) third-generation cephalosporins (2/61; 3.3%) made. The studies on Shigella and Vibrio spp. give a good impres- sion on the evolution of their epidemiology and resistance patterns,particularly in the eastern part of DRC. The resistance patterns of Shigella spp. are in line with those found in the neighbour-ing countries of Rwanda and Burundi, which have historically 4.4.1. Haemophilus influenzae been investigated together with DRC iven the fact that Moraxella catarrhalis these pathogens often act in outbreaks among weakened peo- Seven studies reported on H. influenzae strains, with the ple, these very extensive resistance patterns urge for very tight following mean resistance rates: ampicillin 34.3% (68/198); third- surveillance and frequently updated treatment policies in case of generation cephalosporins 6.2% (6/97); chloramphenicol 11.6% (23/198); gentamicin 41.3% (19/46); and SXT 32.7% (37/113). Screen- Resistance data on the other pathogens were much more scarce ing of respiratory samples from 19 rural Angolan children for the and heterogeneous and displayed wide ranges in resistance rates.
presence of ␤-lactamase in M. catarrhalis revealed a prevalence of Nevertheless, worrying trends are to be noted, especially among Gram-negative enteric organisms. The actual multiresistance pat-terns of NTS and the emerging resistance trends among S. Typhi 5. Discussion and conclusion
isolates are of concern, as many of the widely used cheap first-line antibiotics are no longer active for the treatment of these In this study we reviewed published data on bacterial resistance endemic organisms. In particular, emerging fluoroquinolone resis- in Central Africa. There are several limitations to this study. First, the tance is of concern. With regard to other Enterobacteriaceae and exploration of data was problematic. For logistical reasons we did non-fermentative organisms such as P. aeruginosa, only estimations not search the ‘grey' literature. Owing to historical collaboration and of antimicrobial resistance patterns can be given, but it is clear that institutional and private networks, some countries such as DRC and multiresistant isolates including those with ESBL are present.
Please cite this article in press as: Vlieghe E, et al. Antibiotic resistance among bacterial pathogens in Central Africa: a review of thepublished literature between 1955 and 2008. Int J Antimicrob Agents (2009), ARTICLE IN PRESS
E. Vlieghe et al. / International Journal of Antimicrobial Agents xxx (2009) xxx–xxx In Gram-positive pathogens data are even more scarce and het- [4] Song JH, Chang HH, Suh JY, Ko KS, Jung SI, Oh WS, et al. Macrolide resistance and erogeneous. The real prevalence of colonising and invasive MRSA genotypic characterization of Streptococcus pneumoniae in Asian countries: astudy of the Asian Network for Surveillance of Resistant Pathogens (ANSORP).
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Funding: No funding sources.
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Ethical approval: Not required.
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Intraindividual aqueous flare comparison after implantation of hydrophobic intraocular lenses with or without a&nbsp;heparin-coated surface

Intraindividual aqueous flare comparison after implantation of hydrophobic intraocular lenses with or without a heparin-coated surface Eva M. Krall, MD, Eva-M. Arlt, MD, Gerlinde Jell, MD, Clemens Strohmaier, MD, Alexander Bachernegg, MD, Martin Emesz, MD, G€ unther Grabner, MD, Alois K. Dexl, MD, MSc PURPOSE: To assess the efficacy of a heparin-surface-modified (HSM) hydrophobic acrylicintraocular lens (IOL) (EC-1YH PAL) and the same IOL without heparin coating (EC-1Y-PAL) bythe flare and cell intensity in the anterior chamber after uneventful cataract surgery.

Safety pharmacology — current and emerging concepts

YTAAP-12785; No. of pages: 10; 4C: 3 J. Hamdam et al. / Toxicology and Applied Pharmacology xxx (2013) xxx–xxx Contents lists available at Toxicology and Applied Pharmacology Invited Review Article Safety pharmacology — Current and emerging concepts Junnat Hamdam , Swaminathan Sethu , Trevor Smith , Ana Alfirevic Mohammad Alhaidari , Jeffrey Atkinson , Mimieveshiofou Ayala Helen Box Michael Cross Annie Delaunois Ailsa Dermody ,