Eleven-Year Surveillance of Antibiotic Resistance in Streptococcus pneumoniae in Casablanca (Morocco)
Mohamed Benbachir, Naima Elmdaghri, Houria Belabbes, Ghizlane Haddioui, Hanane Benzaid, and Bahija Zaki
Objective: To analyze trends of antibiotic resistance rates in Streptococcus pneumoniae from 1998 to 2008 in Casablanca (Morocco).Methods: The antibiotic resistance levels of 955 consecutive nonduplicate isolates were studied using E test and disc diffusion methods. Results were interpreted following Clinical and Laboratory Standards Institute guidelines (2005). Analysis was done according to three periods (1998–2001; 2002–2005;
2006–2008), age, and site of infection. Results: Penicillin nonsusceptibility (PNS) increased significantly over time (15.6%, 17.8%, and 24.8%; p=0.003). Levels of PNS have changed as well: in 2006–2008, 9.1% of the isolates had an MIC ‡2mg/ml versus 7.7% in 2002–2005 and 3.4% in 1998–2001. The PNS increase was particularly marked in pediatric isolates (21.4%, 25.5%, and 43.3%; p=0.001). There was no significant dif- ference between the rates of PNS in invasive and noninvasive isolates from children, whereas in adults noninvasive isolates were more penicillin nonsusceptible. Amoxicillin and ceftriaxone nonsusceptible isolates were very rare. An increase of resistance rates was also noticed for erythromycin (9.4%, 12.2%, and 14.4%), tetracycline (20%, 18.6%, and 30.5%), and chloramphenicol (5.6%, 5.6%, and 8.1%). Trimethoprim-sulfa- methoxazole resistance rates remained stable (22.8%, 20%, and 23.8%). Proportions of dual nonsusceptibility to penicillin and erythromycin, increased from 5.6% to 8.9%. Multiple drug resistance (resistance to 3 or more antibiotic classes) was found in 0%, 2.4%, and 7.7% of all isolates, respectively. Conclusion: The results reported here maybe useful for guiding update of treatment recommendations and suggest the need for continuous surveillance. Increase of antibiotic resistance correlated with antibiotic consumption, stressing the need for elaboration of antibiotic policy in Morocco.
Introduction
S
treptococcus pneumoniae is responsible for high morbidity and mortality due to community acquired infections—mainly otitis media—community acquired pneumonia, and meningitis (9,10).Antibiotic resistance inS. pneumoniaehas been increasing regularly over the last three decades, with marked geo- graphic variations and very high levels in some areas (4).
This situation stresses the need for local data to guide treatment recommendations.
Data from North Africa, and especially Morocco, are scarce, and the rare published studies are sporadic and in- clude relatively small numbers of isolates (3,11).
In Casablanca (Morocco), the surveillance of antibiotic resistance inS. pneumoniaestarted in 1994 (1,2) and showed relatively low levels of penicillin nonsusceptibility (PNS), 12.5% and 9.2%, respectively.
We report on an 11-year study ofS. pneumoniaeantibiotic resistance conducted at the Ibn Rochd University Hospital of Casablanca (1998–2008).
Materials and Methods
The Ibn Rochd University Hospital of Casablanca (Morocco) is a tertiary care hospital comprising of 1,600 beds of which 240 are pediatric. This bed capacity repre- sents 57.9% of public health acute care beds of the Grand Casablanca.
From January 1998 to December 2008, all the isolates of S. pneumoniaerecovered at the microbiology laboratory were included. Duplicate isolates were excluded from this study.
Isolates recovered from patients’ £14 years of age were considered pediatric isolates. Isolates recovered from nor- mally sterile sites (cerebrospinal fluid, blood, pleural fluids, and articular fluids) were considered invasive. Resistance
Laboratoire de Microbiologie, Centre Hospitalier Universitaire Ibn Rochd, Casablanca, Morocco.
MICROBIAL DRUG RESISTANCE Volume 18, Number 2, 2012 ªMary Ann Liebert, Inc.
DOI: 10.1089/mdr.2011.0130
157
rates have been analyzed according to three periods: 1998–
2001, 2002–2005, and 2006–2008.
Isolation and identification of S. pneumoniae have been realized by standard methods (a hemolysis, optochin sus- ceptibility, and bile solubility). Antibiotic susceptibility test- ing was done following Clinical Laboratory Standard Institute guidelines (6). Oxacillin (1mg), erythromycin, tetra- cycline, and trimethoprim-sulfamethoxazole were tested by disk diffusion with antibiotic disks from Biorad on Mueller Hinton Agar (BioMerieux) supplemented with 5% sheep blood. Minimal inhibitory concentrations for penicillin G, amoxicillin, and ceftriaxone have been determined on 5% sheep blood Mueller Hinton Agar with E tests from AB Biodisk.
The breakpoints used for interpretation were those re- commended by the Clinical and Laboratory Standards In- stitute in 2005: £0.06 and ‡2mg/ml for penicillin; for amoxicillin £2 and ‡8mg/ml for nonmeningeal isolates; for ceftriaxone £0.5 and ‡2mg/ml for meningeal isolates and
£1 and ‡4mg/ml for nonmeningeal isolates.
Quality control was done withS. pneumoniaeATCC 49619.
Data were analyzed with WHONET5 and EpiInfo 6.4 software. Statistical comparisons were done by the Chi- square test andp£0.05 was considered significant.
Results
During the survey period, a total of 995 nonrepetitive isolates were studied: 33% (n=315) were recovered from children, and 55.6% (n=531) originated from invasive in- fections (Table 1). The numbers of isolates from each period were very similar (Table 2).
PNS rates, all ages included, increased over time, slightly in the beginning from 15.6% during the first period (1998–
2001) to 17.8% during the years 2002–2005 and more signif- icantly (p=0.003) in the third period (2006–2008) with 24.8%.
Furthermore, the level of PNS has changed as well: 3.4% of the isolates had an MIC ‡2mg/ml in 1998–2001 versus 7.7%
in 2002–2005 and 9.1% in 2006–2008.
PNS rates in adults remained stable during the three study periods whereas the rates of PNS were significantly higher in isolates recovered from children (21.4% vs. 25.5% and 43.3%;
p=0.001).
There was no significant difference between the rates of PNS in invasive and noninvasive isolates when all age groups or children were considered (Table 3). In adults, noninvasive isolates were more penicillin nonsusceptible (p=0.03).
Nonsusceptibility to amoxicillin and ceftriaxone was very rare, accounting for less than 1% each (Table 4). During the whole study period, only five isolates were amoxicillin re- sistant (two high level and three low level). Eight isolates were ceftriaxone resistant (three high level and five low level).
Trends in resistance to antibiotics other than penicillin (Table 4) showed that over time, resistance to trimethoprim- sulfamethoxazole remained relatively stable, around 20%, whereas the rates of resistance to chloramphenicol slightly increased (5.6% vs. 5.6% and 8.1%). Resistance to erythro- mycin was more marked (9.4% vs. 12.2% and 14.4%), whereas resistance to tetracycline increased significantly (20% vs. 18.6% and 30.5%).
Proportions of dual nonsusceptibility, defined as penicillin intermediate or resistant together with erythromycin resis- tance, increased from 5.6% to 8.9%. Multiple drug resistance (resistance to three or more antibiotic classes) was found in 0% versus 2.4% and 7.7% of all isolates, respectively.
Penicillin nonsusceptibleS. pneumoniaeisolates were more resistant to other antibiotic classes than penicillin susceptible Table1. Origin of955Streptococcus pneumoniae
Isolates from1998to2008in Casablanca ( Morocco) Children (n) Adults (n) Total (n)
Invasive samples 252 279 531
CSF 144 127 271
Blood 77 95 172
Biological fluids 31 57 88
Noninvasive samples 63 361 424
Respiratory tract samples 46 297 343
Pus 15 58 73
Otitis media samples 2 6 8
Total 315 640 955
Table2. Penicillin Nonsusceptibility Rates inStreptococcus pneumoniaeIsolates According to Age
1998–2001 2002–2005 2006–2008
All ages
n 311 331 313
Total % PNSSP (I+R) 15.6 (12.2+3.4) 17.8 (10.1+7.7) 24.8 (15.7+9.1) Children
n 89 117 109
Total % PNSSP (I+R) 21.4 (14.3+7.1) 25.5 (13.2+12.3) 43.3 (28.9+14.4) Adults
n 222 214 204
Total % PNSSP (I+R) 13 (12+1) 14 (9.3+4.7) 14.9 (8.7+6.2)
PNSSP, penicillin nonsusceptibleStreptococcus pneumoniae.
Table3. Penicillin Nonsusceptibility Rates (%) inStreptococcus pneumoniaeAccording
to Type of Isolates
Invasive (n=531) Noninvasive (n=424) p
All ages 19.8 19.1 0.79
Adults 10.7 16.6 0.03
Children 29.8 33.3 0.58
158 BENBACHIR ET AL.
ones for erythromycin, tetracycline, trimethoprim-sulfa- methoxazole, and less markedly for chloramphenicol (Table 5). Among penicillin susceptible isolates, no one showed a decreased susceptibility to amoxicillin or ceftriaxone.
Discussion
The 11-year survey of antibiotic resistance inS. pneumoniae conducted at the Ibn Rochd University Hospital of Casa- blanca (Morocco) showed an increase of resistance to peni- cillin, erythromycin, tetracycline, and chloramphenicol.
Resistance to amoxicillin and ceftriaxone was marginal. Pe- nicillin nonsusceptible isolates are more resistant to other antibiotics than susceptible isolates, making therapeutic op- tions more problematic. Increases in dual and multidrug resistance were noticed as well, making antibiotic choice even more difficult.
The increase of antibiotic resistance inS. pneumoniaehas been attributed to several factors, including sociocultural and economic factors and differences in regulatory practices (8).
Among these factors, the role of antibiotic consumption has been amply demonstrated (9,12). A recent European study showed that variations of antibiotic consumption are well correlated toS. pneumoniaePNS rates at country level (12).
Antibiotic consumption should be considered according to the volume and the pattern use (12): the much lower rates of PNS in S. pneumoniae in Germany compared with France have been linked to the lower volume of overall antibiotic use and to the relative higher use of narrow spectrum pen- icillins and much lower use of broad spectrum penicillins in Germany. In Morocco, antibiotic consumption has sharply increased: from 7.01 DDD/1,000 inhabitants (DID) in 1999 to 9.96 DID in 2004 (7). In Casablanca, the economic capital of Morocco, in 2004 the antibiotic consumption was 2.4 times higher than the mean for the whole country and the volume of large spectrum penicillins ( J01CA of the WHO ATC classification) almost tripled (5.43 DDI vs. 14.23 DID) be-
tween 1994 and 2004. The correlation between antibiotic use and antibiotic resistance in S. pneumoniae showed in this survey was suggested as well for amoxicillin resistance in Escherichia coli responsible for community acquired urinary tract infections in Casablanca (7).
Antibiotic resistance rates vary considerably according to geographic location. In Morocco, other data are available only from the capital Rabat: a study conducted between 1997 and 2001 on 90 isolates (11) reported slightly lower rates (7.8% of PNSP) than to those observed in Casablanca in 1994–1997 (1). A more recent study (2006–2007) of 85 respi- ratory isolates showed 40%, 14.1%, and 13% for penicillin, amoxicillin, and cefotaxime nonsusceptibility (3). The rea- sons for such higher rates and such sharp trends are not clear, apart from the respiratory origin of the isolates. On the other part, multicentric surveys in the Mediterranean region showed a very heterogeneous situation (4). Other studies showed that remarkably different rates can be found in re- gions from the same country (5).
Young age is one of the multiple risk factors linked to antibiotic resistance in S. pneumoniae (9). Results from our series are concordant, since PNS rates were much more higher in pediatric isolates (43.3% vs. 14.9%).
Resistance is more frequent in noninvasive isolates, espe- cially from respiratory tract (9). In our series, similar results were noticed only in adults. The discrepant result found in children may be due to the fact that only 20% of the isolates tested in this age group were noninvasive and that the per- centage of isolates from otitis media was very low.
The data reported here maybe useful for guiding the elaboration of local treatment recommendations, and for monitoring the antibiotic resistance trends after the intro- duction of the pneumococcal vaccine in the Moroccan na- tional immunization program.
Data on antibiotic resistance ofS. pneumoniaein Morocco are now available only from the administrative and eco- nomic capitals and need to be completed with results from other regions, which suggests the establishment of a national network of laboratories using the same protocols to allow for comparison.
Author Disclosure Statement
This study was funded in part by Glaxo Smith Kline Beecham, Morocco.
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Address correspondence to:
Naima Elmdaghri, Ph.D.
Laboratoire de Microbiologie Centre Hospitalier Universitaire Ibn Rochd Casablanca 20000 Morocco E-mail:naimaelmdaghri@yahoo.fr
160 BENBACHIR ET AL.
