{"id":48216,"date":"2023-03-21T11:10:24","date_gmt":"2023-03-21T11:10:24","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=48216"},"modified":"2023-04-01T06:16:56","modified_gmt":"2023-04-01T06:16:56","slug":"antibiotic-resistance-of-streptococcus-pneumoniae-neisseria-meningitidis-haemophilus-influenzae-and-staphylococcus-aureus-in-morocco-national-data-meta-analysis","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no1\/antibiotic-resistance-of-streptococcus-pneumoniae-neisseria-meningitidis-haemophilus-influenzae-and-staphylococcus-aureus-in-morocco-national-data-meta-analysis\/","title":{"rendered":"Antibiotic Resistance of Streptococcus Pneumoniae, Neisseria Meningitidis, Haemophilus Influenzae and Staphylococcus Aureus in Morocco, National Data: Meta- Analysis."},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Antibiotic resistance is nowadays one of the serious problems in the field of global health. It is reaching significant proportions in all regions of the globe. Each day, new resistance mechanisms appear and spread around the world, compromising\u00a0 ability to treat the most common infectious diseases 1<\/sup>. <\/strong>Antibiotic resistance is reaching high levels worldwide, including Morocco and other neighboring African countries 2<\/sup>, with some bacteria becoming alarmingly multi-resistant to antibiotics 3<\/sup>. <\/strong>A bacterium is said to be resistant when it escapes the action of the supposedly active antibiotic prescribed to the patient, which is manifested by a relative or absolute clinical failure of the antibiotic therapy. In the majority of infections, a clinical failure results in the absence of improvement (fever, general condition) after approximately 72 hours of treatment and the prescription of a second antibiotic.4,5<\/sup><\/p>\n

There are several types of bacterial resistance, for example: natural bacterial resistance, acquired bacterial resistance, resistance by chromosomal mutation, resistance by gene acquisition, cross-resistance, co-resistance and selection 6<\/sup>. Two major reasons influencing this development are the widespread use of antibiotic therapy and the epidemic spread of resistant bacteria. However, other bacterial species long spared by this phenomenon and responsible for community infections (Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), Haemophilus influenzae (H. influenzae) and Staphylococcus aureus <\/em>(S. aureus<\/em>)) have in turn evolved in the direction of resistance 7<\/sup>.<\/strong><\/p>\n

S. pneumoniae <\/em>is a species of bacteria of the genus Streptococcus<\/em>, it is an important pathogen. It is responsible for many infections: for example, it has increased mortality during the Spanish flu pandemic. Its original name was diplodocus pneumoniae<\/em> in 1926, it was named Streptococcus pneumoniae<\/em> in 1974 due to its chain-like growth in liquid media. Because of its involvement as a pathogen in pneumonia, it has long been referred to simply as pneumococcus. Pneumococcal infections are particularly dangerous and very often require hospitalization, with mortality rates ranging from 8 to 15%.8<\/sup>. S. pneumoniae, <\/em>a major cause of community acquired invasive infection for newborns and children. Invasive pneumococcal infections, including meningitis, remain worrisome with a mortality rate of over 8% and a significant risk of complications. Of more than 90 serotypes, only a limited number are responsible for pneumococcal infections. The incidence of serotype may vary depending on the age of the patient, geographic region, and time of surveillance. The advent and introduction of pneumococcal conjugate vaccines has resulted in significant progress in the prevention of pneumococcal 9<\/sup>.<\/p>\n

N. meningitidis, <\/em>known as meningococcus, is a gram-negative diplococcal bacterium known for its role in meningitis. Meningococci are germs found only in humans, in the nasopharynx, where they can cause mild nasopharyngitis or an asymptomatic carrier state. One can remain a carrier for several months or even years. In a normal population, 5-10% of carriers are found, but this rate can reach 50-75% in certain dense communities (barracks, boarding schools). Out of approximately 400 carriers, only one person becomes a victim of a serious meningococcal infection, this is most often presented as acute purulent meningitis.<\/em> The meningococcus could move from the nasopharynx to the meninges by following the path of the olfactory nerves. However, the meningococcus reaches central nervous system (CNS) through bloodstream. Indeed, meningococcal disease almost always present at the beginning of meningitis. This sepsis may be asymptomatic, or it may add to the meningeal syndrome a purpuric eruption (found, depending on the epidemic, in 10 to 50% of cases of meningitis), or in 5 to 10% of cases, it may present as purpura fulminans, rapidly fatal, even before meningitis develops. These superacute forms are referred to as Waterhouse-Friderichsen syndrome. In these cases, the endotoxin, by contracting the intrahepatic veins, causes the accumulation of blood upstream of these veins, resulting in capillary hemorrhages (in the adrenals among others), intravascular thrombosis and circulatory collapse 10,11<\/sup>.<\/strong><\/p>\n

H. influenzae,<\/em> called Pfeiffer’s bacillus, is a bacterium of the family: Pasteurellacae<\/em> and class: Gammaproteobacteria.<\/em> The cells are coccobacilli or small immobile Gram-negative rods. Richard Pfeiffer (1858-1945) was the first to describe them in 1892 from the influenza pandemic of 1889-1892. For a long time, he was believed to be responsible for influenza, until 1931, when Richard Shope isolated a virus from filtrates of pig lung shreds during a swine influenza similar to the human one 12,13<\/sup>. <\/strong>H. influenzae <\/em>is a species sensitive to many families of antibiotics, and has not been spared the evolution of antibiotic resistance. The level of acquired resistance for aminpenicillins, tetracycline and trimethoprim places H. influenzae <\/em>in the species inconsistently susceptible to these antibiotics, this species is naturally resistant to lincosamides and is classified as resistant to macrolides with a 16 atom cycle 14<\/sup>.<\/p>\n

S. aureus <\/em>is most pathogenic species of the genus Staphylococcus<\/em>. It is responsible for localized suppurative infections, food poisoning, and in some extreme cases, infections that could be fatal (immunocompromised patients, cardiac prostheses). S.aureus <\/em>presents itself as a clustered shell (Grape clusters), Gram positive and catalase positive. Its name derives from the golden tint that its carotenoid concentration provides it 15<\/sup>. The S. aureus<\/em> species is commensal to humans (it is present in 15 – 30% of individuals known as healthy carriers in whom it has an ecological protection role), is an opportunistic pathogen in certain locations, under certain circumstances. S.aureus<\/em> a good resistance to natural purification mechanisms (oxidation, desiccation, which explains its direct but also indirect transmission). S.aureus<\/em> is a germ that has developed a remarkable level of resistance against multiple antibiotics, complicating treatment. Historically, S. aureus<\/em> resistance appeared within two years after introduction penicillin 3<\/sup>.<\/strong> Controlling infections caused by antibiotic-resistant bacteria in humans requires regular monitoring of bacterial resistance and control of antibiotic use\u00a016<\/sup>.<\/p>\n

The frequency of the appearance of resistance and multi-resistance is most often conditioned by an increased use of antibiotics. The pressure of these molecules on the bacterial flora seems to be at the origin of the emergence of bacterial resistance. Therefore, on the recommendation of the World Health Organization (WHO), structures for monitoring antibiotic resistance and committees on the proper use of these molecules have been set up in most countries of the world. The objective of these structures is to periodically take stock of bacterial resistance in order to better adapt antibiotic therapy 17,18<\/sup>.<\/p>\n

This paper aim is to make a meta-analysis from the studies done in Morocco on antibiotic resistant bacteria during the last nine years (2011-2020). We were interested in the following bacteria: (S. pneumoniae, N. meningitidis, H. influenzae <\/em>and S. aureus<\/em>) and the evolution this resistance.<\/p>\n

Materials and methods<\/strong><\/p>\n

A thorough meta-analysis of past studies on the topic of bacterial resistance to antibiotics was carried out using national data in Morocco, for relatively common pathogens occasionally responsible for most infectious pathologies (S. pneumoniae, N. meningitidis, H. influenzae and S. aureus<\/em>).<\/p>\n

Type and period of the study<\/strong><\/p>\n

This Meta-analysis on antibiotic resistance in Morocco, national data on studies conducted in the last nine years (2011-2020).<\/p>\n

S<\/strong>earch strategy and criteria for choosing studies<\/strong><\/p>\n

\u00a0<\/strong>Exploitation standards<\/strong><\/p>\n

Collecting articles for our meta-analysis using keywords: bacteria, antibiotic, resistance, S. pneumoniae, N. meningitidis, H. influenzae, and S. aureus<\/em>. Searched for articles and studies in the literature regarding bacterial resistance to antibiotics carried out in Morocco between 2010 and 2020, and we made no distinction regarding the publication’s language.<\/p>\n

Elimination standards<\/strong><\/p>\n

Published data on bacterial resistance to antibiotics, articles or studies that are on animals, outside the selected period, connected to our study but in different directions, and that are not on national data, were excluded. A meta-analysis was performed A meta-analysis was performed\u00a0 for 15 articles published using GraphPad Prisma 19<\/sup>.<\/p>\n

Statistical analysis<\/strong><\/p>\n

For the statistical analysis, we used three different programs including: GraphPad Prisma 9 Review Manager 5.4 and Microsoft Excel, each of which has its own benefits and traits.<\/p>\n

-GraphPad Prisma 9: for repeat and elimination criteria, and to graph years and regions of publication. A p value<\/em> <<\/u>0.05 was regarded as significant for statistical analyzes with a 95% confidence interval (95% CI)<\/p>\n

-Review Manager 5.4: to compare similar studies.<\/p>\n

-Microsoft Excel to create tables, collect and compare data.<\/p>\n

Results and Discussions<\/strong><\/p>\n

Results<\/strong><\/p>\n

Studies published in the period of (2011-2020) in Moroccan regions on antibiotic resistance<\/p>\n\n\n\n
\"Vol16No1_Ant_Abd_fig1\"<\/a><\/td>\nFigure 1:\u00a0Number of studies published in Morocco in period of (2011-2020) on bacterial resistance to antibiotic.<\/strong><\/p>\n

Click here to view Figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Vol16No1_Ant_Abd_fig2\"<\/a><\/td>\nFigure 2:\u00a0Number of studies published in Moroccan cities on bacterial resistance to antibiotic in period of (2011-2020).<\/strong><\/p>\n

Click here to view Figure\u00a0<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Studies characteristics that were considered in our meta-analysis<\/strong><\/p>\n

The 15 studies’ primary characteristics (in four Moroccan regions) within scope of this systematic review. Essentially all of these were based on laboratory controls, analytical research and diagnostic surveys as illustrated in (Figure 3).<\/p>\n\n\n\n
\"Vol16No1_Ant_Abd_fig3\"<\/a><\/td>\nFigure 3: PRISMA Graph for the selection of studies: shows the number of researches or studies included in our search of literature on bacterial resistance to antibiotic, the processing of the data, and the elimination criteria, which led to the selection of 15 studies for our meta-analysis.<\/strong><\/p>\n

Click here to view Figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Characteristics of the studies included in our analysis on antibiotic resistance<\/strong><\/p>\n

In each article, indicated the region and year of the study, the germs studied, the antibiotics, the most resistant bacteria, the number of references on which each research was based and the number of samples in each study. And we added comments for each reference.\u00a0<\/strong><\/p>\n

Table <\/strong>1<\/strong>: Summary of studies that were listed in our meta-analysis<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
References<\/strong><\/td>\nYear of publication<\/strong><\/td>\nRegion<\/strong><\/td>\nN. of Samples<\/strong><\/td>\nMicrobe<\/strong><\/td>\nTypes of Antibiotics<\/strong><\/td>\nResistance<\/strong><\/td>\nComments<\/strong><\/td>\n<\/tr>\n
Bouskraoui et al<\/em> 20<\/sup><\/strong><\/td>\n2011<\/td>\nMarrakech<\/td>\n302<\/td>\nStreptococcus pneumoniae<\/em><\/td>\nPG<\/td>\nPG<\/td>\npenicillin resistance of carrier strains in children under 2 years old<\/td>\n<\/tr>\n
N. Mdaghri et al<\/em>.21<\/sup><\/strong><\/td>\n2012<\/td>\nCasablanca<\/td>\n185<\/td>\nNeisseria meningitidis<\/em><\/td>\nPG<\/td>\nPG<\/td>\nIn this study, the only antibiotic, penicillin G, gave significant resistance<\/td>\n<\/tr>\n
Benbachir et al<\/em>.22<\/sup><\/strong><\/td>\n2012<\/td>\nCasablanca<\/td>\n955<\/td>\nStreptococcus pneumoniae<\/em><\/td>\nPNS, AMC, CRO, CHL, ERY, TET and TSU<\/td>\nPNS, AMC, CRO, ERY<\/td>\nAntibiotic resistance rates vary considerably by geographic location at MIC>2\u03bcg\/ml<\/td>\n<\/tr>\n
Diawara et al<\/em>. 23<\/sup><\/strong><\/td>\n2016<\/td>\nCasablanca<\/td>\n655<\/td>\nStreptococcus pneumoniae<\/em><\/td>\nMLSB<\/td>\nMLSB<\/td>\nMulti-resistant S.pneumoniae. <\/em>Strains include both (vaccine and non-vaccine) serotypes. More observationnel studies are needed<\/td>\n<\/tr>\n
Diawara et al<\/em>.24<\/sup><\/strong><\/td>\n2017<\/td>\nCasablanca<\/td>\n361<\/td>\nStreptococcus pneumoniae<\/em><\/td>\nPGand \u00a0AMP<\/td>\nPG<\/td>\nThe ratio was 22.2% overall for PG resistance in the research<\/td>\n<\/tr>\n
Ghita Y et al.<\/em> 25<\/sup><\/strong><\/td>\n2017<\/td>\nFes<\/td>\n123<\/td>\nHaemophilus influenzae<\/em><\/td>\nNo resistance<\/p>\n

sensitive<\/td>\n

sensible<\/td>\nH.influenzae, <\/em>plays a major role in lower respiratory infections, these infections are a real public health problem.<\/td>\n<\/tr>\n
Moumni M B et al<\/em>.26<\/sup><\/strong><\/td>\n2018<\/td>\nFes<\/td>\n277<\/td>\nNeisseria meningitidis<\/em><\/td>\nCET<\/td>\nsensible<\/td>\nFollowing this study, we can conclude that the therapeutic regimens using 3rd generation cephalosporins in the treatment of community meningitis are effective. We also suggest the reinforcement of the vaccination program against H. influenzae<\/em> b<\/em>.<\/td>\n<\/tr>\n
EL Amin G et al.,27<\/sup><\/strong><\/td>\n2019<\/td>\nRabat<\/td>\n2436<\/td>\nStreptococcus pneumoniae and \u00a0Neisseria meningitidis<\/em><\/td>\nPG<\/td>\nPG<\/td>\nNosocomial meningitis represents 73.8% of documented meningitis in this series. Many of them are related to neurosurgery or consecutive to the placement of a CSF shunt.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Continue table (<\/strong>1<\/strong>): Summary of studies that were listed in our meta-analysis<\/strong>:<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
References<\/strong><\/td>\nYear of publication<\/strong><\/td>\nRegions<\/strong><\/td>\nN. of Samples<\/strong><\/td>\nMicrobe<\/em><\/strong><\/td>\nTypes of Antibiotics<\/strong><\/td>\nResistance<\/strong><\/td>\nComments<\/strong><\/td>\n<\/tr>\n
Rhars A et al.<\/em> 28<\/sup><\/strong><\/td>\n2019<\/td>\nRabat<\/td>\n100<\/td>\nStaphylococcus aureus<\/em><\/td>\nPEN, CIP et ERY<\/td>\nPEN, CIP<\/td>\nThe need to adapt probabilistic treatment regimens to the local epidemiology.<\/td>\n<\/tr>\n
Kouara S et al.<\/em>\u00a029<\/sup><\/strong><\/td>\n2019<\/td>\nFes<\/td>\n46<\/td>\nStaphylococcus aureus<\/em><\/td>\nPEN, CIP et \u00a0ERY<\/td>\nPEN, CIP, ERY<\/td>\nThis class of antibiotics still retains its place in the treatment of staphylococci<\/td>\n<\/tr>\n
Nzoyikorera N et al<\/em>\u00a030<\/sup><\/strong><\/td>\n2019<\/td>\nCasablanca<\/td>\n74<\/td>\nStreptococcus pneumoniae<\/em><\/td>\nPG<\/td>\nPG<\/td>\nThe data from this study on adult MS show variability in serotypes and provide information on the antibiotic susceptibility status of pneumococcus in adults<\/td>\n<\/tr>\n
\n

Raghani A et al<\/em>. 31<\/sup><\/strong><\/p>\n<\/td>\n

2019<\/td>\nRabat<\/td>\n4232<\/td>\nStreptococcus pneumoniae<\/em><\/td>\nPG<\/td>\nPG<\/td>\nThe importance of the frequency of pneumopathies as well as the isolation of resistant germs incites us to improve the hygiene conditions, the means of prevention and the reasoned prescription of antibiotics<\/td>\n<\/tr>\n
\n

Saoud M Z et al.<\/em><\/strong> 32<\/strong><\/sup><\/p>\n<\/td>\n

2019<\/td>\nRabat<\/td>\n119<\/td>\nStaphylococcus aureus<\/em><\/td>\nPEN, CIP et ERY<\/td>\nPEN, CIP et ERY<\/td>\n\n

All prescribed antibiotics were resisted by S. aureus<\/p>\n<\/td>\n<\/tr>\n

Ait Mouss et al.<\/em><\/strong> 33<\/strong><\/sup><\/td>\n2020<\/td>\nCasablanca<\/td>\n245<\/td>\nNeisseria meningitidis<\/em><\/td>\nPG et 3GCs<\/td>\nPG<\/td>\n\n

All isolated strains are sensitive to third generation cephalosporin.<\/p>\n<\/td>\n<\/tr>\n

Ousaid et al<\/em>.\u00a03<\/sup><\/strong><\/td>\n2020<\/td>\nCasablanca<\/td>\n115<\/td>\nStaphylococcus aureus<\/em><\/td>\nOXA, AMP, AMX,<\/p>\n

CTX, SEF et ERY<\/td>\n

OXA, AMP, AMX, CTX et SEF<\/td>\nIn Morocco and neighboring countries, the problem of antibiotic resistance is recognized and well documented.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Abbreviations: PEN\u00a0: penicillin, PG\u00a0: Penicillin G, SEF\u00a0: Cefpodoxime, CHL\u00a0: Chloramphenicol, ERY\u00a0: erythromycin, TET\u00a0: Tetracyclin, OXA\u00a0: Oxacillin, AMP\u00a0: ampicillin, CIP\u00a0: Ciprofloxacin, CTX\u00a0: Cefotaxime, AMX\u00a0: amoxicillin, CET\u00a0: Ceftriaxon, MLSB\u00a0: macrolide,\u00a0 lincosamides , streptogramin B et C3G\u00a0: cephalosporins 3rd generation.<\/p>\n

Epidemiological profile of invasive germs in the pediatric <\/strong><\/p>\n

Bacterial meningitis in the pediatric population remains a worrying pathology due to its frequency and severity, studies made on the antimicrobial resistance of the most frequent bacteria in hospitals in Morocco, and these studies have concluded that the most frequent bacteria: S. pneumoniae; N. meningitidis and H. influenzae.<\/em><\/p>\n

According to these studies, which are presented in the table below, the prevalence of S. pneumonia<\/em>e was 13%, N. meningitidis <\/em>was 9.7%, and H. influenzae<\/em> was 5.4% in Casablanca in 2012 (based on 185 samples).<\/p>\n

In 2018, in Morocco, (out of 277 samples), S. pneumoniae<\/em> infection was confirmed 29%, N. meningitidis<\/em> infection was 33% and H. influenzae<\/em> infection was 8%.<\/p>\n

In 2016, a study was conducted in Rabat on 25 samples, half of the samples were infected with S. pneumoniae<\/em> at 48%, N. meningitidis<\/em> at 24% and H. influenzae<\/em> at 8%.<\/p>\n

According which studies (2012, 2018), ceftriaxone was used in the treatment in both studies and the outcome was favorable in all patients. Both studies concluded that C3Gs are the most effective treatment for bacterial meningitis and suggested that the vaccination program against H. Influenzae<\/em> b should be strengthened.<\/p>\n

Table <\/strong>2<\/strong>:<\/strong> Epidemiological profile of invasive germs in the pediatric.<\/strong>\u00a0<\/em><\/strong><\/p>\n\n\n\n\n\n\n
References<\/strong><\/td>\nYears<\/strong><\/td>\nRegions<\/strong><\/td>\nN. of samples<\/strong><\/td>\nS. pneumoniae<\/em><\/strong><\/td>\nN. meningitidis<\/em><\/strong><\/td>\nH. influenzae<\/em><\/strong><\/td>\n<\/tr>\n
Mdaghri N, et al<\/em> 2012<\/strong><\/td>\n2012<\/td>\nCasablanca<\/td>\n185<\/td>\n13%<\/td>\n9.7%<\/td>\n5.4%<\/td>\n<\/tr>\n
EL Amin G et al 2019<\/em><\/strong><\/td>\n2016<\/td>\nRabat<\/td>\n25<\/td>\n48%<\/td>\n24%<\/td>\n8%<\/td>\n<\/tr>\n
Moumni M B,<\/strong><\/p>\n

et al<\/em><\/strong> 2018<\/strong><\/td>\n

2018<\/td>\nFes<\/td>\n277<\/td>\n29%<\/td>\n33%<\/td>\n8%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Evolution of S. pneumoniae<\/em> resistance to antibiotics<\/strong><\/p>\n

The period of realization of the two studies is about seven years, where the resistance of bacteria was studied on both penicillin and erythromycin, at the beginning of the two studies the rate of bacterial resistance to penicillin was 25% and after about seven years was 31%.The rate of resistance to erythromycin was 15% and after seven years was 21%, therefore, there is a remarkable increase in bacterial resistance to the aforementioned antibiotics, which imposes attention to the use antibiotic in treatment S. pneumoniae<\/em> infection and evaluation effectiveness treatment and antibiotic resistance heterogeneity.<\/p>\n\n\n\n
\"Vol16No1_Ant_Abd_tab3\"<\/a><\/td>\nTable <\/strong>3<\/strong>: Resistance of S.pneumoniae<\/em> to antibiotics<\/strong><\/p>\n

Click here to view Table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0Resistance of S. pneumoniae<\/em> to penicillin G<\/strong><\/p>\n

Through previous studies carried out from 2011 until 2020 on 302 samples, S. pneumoniae<\/em> was the most resistant to Penicillin G, in 2011 the percentage of resistance to Penicillin G was at 2.7%, and in the second study carried out on 101 samples this resistance evolved to 100% in 2020.<\/p>\n

Table <\/strong>4<\/strong>:<\/strong> Resistance of S. pneumoniae<\/em> to penicillin G: (SPRPG).<\/strong>\u00a0<\/strong><\/p>\n\n\n\n\n\n\n\n\n
References<\/strong><\/td>\nYears<\/strong><\/td>\nRegions<\/strong><\/td>\nN. of samples<\/strong><\/td>\nS<\/em><\/strong>.<\/em><\/strong> \u00a0<\/em><\/strong>pneumoniae<\/em><\/strong><\/td>\nRPG<\/strong><\/td>\n<\/tr>\n
Bouskraoui Met al 2011<\/em><\/strong><\/td>\n2011<\/td>\nMarrakech<\/td>\n302<\/td>\n45.8%<\/td>\n2.7%<\/td>\n<\/tr>\n
Raghani A et al.<\/em>2019<\/strong><\/td>\n2012-2018<\/td>\nRabat<\/td>\n4232<\/td>\n1%<\/td>\n10.6%<\/td>\n<\/tr>\n
Diawara et al<\/em>,\u00a0 2017<\/strong><\/td>\n2014<\/td>\nCasablanca<\/td>\n361<\/td>\n100%<\/td>\n22.2%<\/td>\n<\/tr>\n
Nzoyikorera N et al<\/em>.2019<\/strong><\/td>\n2016-2018<\/td>\nCasablanca<\/td>\n74<\/td>\n32%<\/td>\n18.75<\/td>\n<\/tr>\n
Ousaid et al<\/em>, 2020<\/strong><\/td>\n2020<\/td>\nCasablanca<\/td>\n101<\/td>\n86%<\/td>\n100%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0Evolution of N.meningitidis<\/em> resistance to penicillin G<\/strong><\/p>\n

Three studies on non-tuberculous bacterial meningitis in pediatric in two Moroccan regions (Casablanca and Fes), found that resistance of N. meningitidis<\/em> to penicillin G was 4.3 in 2000, 11.1% in 2012, 16.6% in 2016, and 24% in 2019.<\/p>\n

Table <\/strong>5<\/strong>:<\/strong> Resistance of N. meningitidis <\/em>\u00a0to penicillin G: (NMRPG).<\/strong><\/p>\n\n\n\n\n\n\n
References<\/strong><\/td>\nYears<\/strong><\/td>\nN. of samples<\/strong><\/td>\nRegions<\/strong><\/td>\nRPG<\/strong><\/td>\n<\/tr>\n
N. Mdaghri, et al<\/em> 2012<\/strong><\/td>\n2012<\/td>\n180\/18<\/td>\nCasablanca<\/td>\n11.1%<\/td>\n<\/tr>\n
EL Amin G et al<\/em> 2019<\/strong><\/td>\n2016<\/td>\n600\/6<\/td>\nFes<\/td>\n16.6%<\/td>\n<\/tr>\n
K. Ait Mouss et al<\/em> 2020<\/strong><\/td>\n2019<\/td>\n245<\/td>\nCasablanca<\/td>\n24%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Evolution of H. Influenzae<\/em> resistance to antibiotics<\/strong><\/p>\n

Epidemiological profile of lower respiratory infections with H. influenzae<\/em><\/strong><\/p>\n

A study carried out in the period 2011-2016 on 123 strains of H. influenzae<\/em> responsible for lower respiratory infections, this study showed that the strains that are resistant to amoxicillin are sensitive to the combination amoxicillin-clavulanic acid 28% of cases, and the resistance to other antibiotics 16% to trimethoprim -sulfamethoxazole, 4.8% to fluoroquinolones 2.5% to tetracyclins, and no resistance to 3rd generation cephalosporins was observed.<\/p>\n

Table\u00a06: Epidemiological profile of lower respiratory infections with H. influenzae.<\/em><\/strong><\/p>\n\n\n\n\n
References<\/strong><\/td>\nYears<\/strong><\/td>\nRegion<\/strong><\/td>\nN. of Samples<\/strong><\/td>\nRAMX<\/strong><\/td>\nRTRM &RSU<\/strong><\/td>\nRFLQ<\/strong><\/td>\nRTET<\/strong><\/td>\nC 3 G<\/strong><\/td>\n<\/tr>\n
Ghita Y<\/strong> et al<\/em> <\/strong>2017<\/strong><\/td>\n2011 -2016<\/td>\nFes<\/td>\n123<\/td>\nS:AMC28 %<\/td>\n16%<\/td>\n4,8%<\/td>\n2,5%<\/td>\nS<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Abbreviations: R: Resistance, S: Sensibles, AMX: amoxicillin, SU: sulfamethoxazole, FLQ: fluoroquinolones, TET: Tetracyclin, AMC: amoxicillin-clavulanic and TRM: The resistance of trimethoprim<\/p>\n

Epidemiological profile meningitis of H. influenzae<\/em> bacterial<\/strong><\/p>\n

The data of the retrospective studies carried out in Rabat over a period of three years based on CSF analysis of 95 positive cases were documented (59 adults and 36 children) of which the percentage of H. Influenzae<\/em> cases was 8% (2 cases) and the antibiotic resistance was not documented, and in the second study carried out in Fes, showed that CSF analysis of 24 positive cases, of which the percentage of H. Influenzae<\/em> cases was 8%, and the antibiotic resistance was not documented. It can be concluded that there is a lack of study of the resistance of H. Influenzae<\/em> to antibiotics in these two studies Table 7.<\/p>\n

Table 7: Epidemiological profile meningitis of H. influenzae<\/em> bacterial<\/strong><\/p>\n\n\n\n\n\n
References<\/strong><\/td>\nYears<\/strong><\/td>\nRegions<\/strong><\/td>\nN. of Samples<\/strong><\/td>\nH.influenzae<\/em><\/strong><\/td>\n<\/tr>\n
El amin G et al<\/em> 2019<\/strong><\/td>\n2016 – 2018<\/td>\nRabat<\/td>\n600<\/td>\n8%<\/td>\n<\/tr>\n
Moumni M B, et al<\/em> 2018<\/strong><\/td>\n2018<\/td>\nFes<\/td>\n277<\/td>\n8%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0Evolution of S. aureus<\/em> resistance to antibiotics:<\/strong><\/p>\n

S. aureus <\/em>is the main cause of nosocomial infections and can affect several parts of the body and the emergence of resistant strains is a major problem in the public health of all the world that continues to increase according to the data of previous studies.<\/p>\n

A study conducted over a period of 2016-2018 in Rabat, on 117 samples taken in consulting rooms and emergency cases with an average age of 47 years, where S. aureus<\/em> was 92%, and tests were performed to determine its resistance to antibiotics, the percentage of resistance to penicillin G was 92%, to ciprofloxacin at 16.5%, and erythromycin at 14.6%.<\/p>\n

Another study in Rabat conducted from 2017-2019 (Table 8) and the mean age of patients 49 year, and the samples were on patients with abscesses, diabetic foot and cellulitis, 29% of these samples were to S. aureus<\/em>, and tests were performed showing that resistance to penicillin G was 89.6%, and to ciprofloxacin 6.9%, and resistance to erythromycin was not tested.<\/p>\n

In another study conducted from 2018-2019 in Fes, on 46 samples of urine and venous catheters in people with an average age of 46 years, all samples contained S. aureus<\/em> and were resistant to erythromycin to 88%, and ciprofloxacin 4% and penicillin G 2%.<\/p>\n

Table 8: Resistance of S. aureus<\/em> to antibiotics<\/strong><\/p>\n\n\n\n\n\n\n
References<\/strong><\/td>\nYears<\/strong><\/td>\nRegions<\/strong><\/td>\nInfectious pathologies<\/strong><\/td>\nN. of Samples<\/strong><\/td>\nRPENG<\/strong><\/td>\nRCIP<\/strong><\/td>\nRERY<\/strong><\/td>\n<\/tr>\n
Saoud M Z et al<\/em>.2019<\/strong><\/td>\n2016-2018<\/td>\nRabat<\/td>\nSurgical operations and emergencies<\/td>\n117<\/td>\n92%<\/td>\n16.51%<\/td>\n14.61%<\/td>\n<\/tr>\n
Rhars A et al<\/em> 2019<\/strong><\/td>\n2017-2019<\/td>\nRabat<\/td>\nDiabetic foot abscess and cellulitis<\/td>\n100<\/td>\n89.6<\/td>\n6.9%<\/td>\n–<\/td>\n<\/tr>\n
Kouara S et al 2019<\/em><\/strong><\/td>\n2018-2019<\/td>\nFes<\/td>\nIntravenous catheters and urine cultures<\/td>\n46<\/td>\n2%<\/td>\n4%<\/td>\n88%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Abbreviations: PEN\u00a0G: penicillin G, ERY: erythromycin CIP: ciprofloxacin.<\/p>\n

Discussion<\/strong><\/p>\n

In our analysis of national data on bacterial resistance to antibiotics, we chosen 15 articles conducted over the previous ten years in four Moroccan regions, analyzed and compared the data from these studies to learn about antibiotic-resistant germs and the kinetics of this resistance, rapid emergence of resistant bacteria is occurring global, including in Morocco and neighboring countries, jeopardizing the effectiveness of antibiotics which have revolutionized medicine and let millions of people live longer 34<\/sup>. Misuse of these medications has been linked to the challenge of antibiotic resistance. In addition, paucity of development of new drugs due to weaker economic incentives and onerous regulatory requirements by the pharmaceutical industry, is a serious problem 35<\/sup>. The usage of antibiotics has a massive effect on these parameters, which has been extensively proven in Morocco 36<\/sup>.<\/p>\n

Based our meta-analysis on the evaluation of the evolution of resistance of S. pneumoniae, N. meningitidis, H. influenzae, <\/em>and S. aureus<\/em>.<\/p>\n

According the results obtained from the studies carried out in Morocco, we can say for the different bacteria, the prevalence of resistance increases with the years, in fact, in 2012 it was (13%, 9.7%, 5.4%) respectively S. pneumoniae, N. meningitidis and H. influenzae<\/em>, in 2016 (48%, 24%, 8%) and in 2018 (29%, 33%, 8%), and we did not find documents on the prevalence of S.aureus<\/em>.<\/em><\/p>\n

We noticed that the evolution of resistance regarding S. pneumoniae<\/em> was impacted by the introduction of the vaccine, rate of resistance S. pneumoniae<\/em> to antibiotic erythromycin before vaccination was 76% and after the introduction of the vaccine decreased to 61%, and the incidence of pneumonia was 17.7% and after vaccination decreased to 10.2%. The resistance of S. pneumoniae<\/em> to penicillin G, increased from 2.7% in 2011 to 100% in 2020,in addition, the study documented high rates of resistant to penicillin\u00a0 of S. pneumoniae<\/em>\u00a0 in Spain [37], in Algeria, Egypt, Morocco and Senegal [3]. Increase in antibiotic resistance for S. pneumoniae<\/em> has been attributed to several factors, differences in regulatory practices, economic factors and\u00a0 including sociocultural factors in France and Germany 37<\/sup>.<\/p>\n

For N. meningitidis<\/em>, there is an increase in resistance to penicillin G in Morocco where in 2012 was 11.1% to 24% in 2019. In USA the rate of resistance was 10.3% 36<\/sup>. <\/strong>N. meningitidis <\/em>resistant to Penicillin G have become frequent and total resistance is increasing in Belgium to 4.8% 38,39<\/sup>, in Canada, 21.7% [40], and over the past 2 decades, an increase in penicillin G resistance has been observed in many parts of the world, with a higher rate in Europe 41,42<\/sup>. Penicillin resistance in N. meningitidis <\/em>due to beta-lactamase production remains relatively rare. Isolates with resistance and reduced susceptibility to penicillin G due to alterations in the PENA gene (encoding penicillin binding protein 2) are reported, in 2016, a penicillin resistant clade of isolates MENW: CC11 with altered PENA genes was identified in Australia. most recent recently,\u00a0 increase in penicillin resistant invasive isolates of MENW:CC11 has been noted in England 43<\/sup>. Currently in France, the progressive, of the number of strains of decreased sensitivity with penicillins, the appearance of resistant strains to the penicillin G, make reconsider the problem of the sensitivity and resistance N. meningitidis<\/em> to penicillin G 44<\/sup>.<\/strong><\/p>\n

Studies conducted from 2011 to 2016 in Morocco on H. influenzae<\/em> resistance to antibiotics, we found that resistance for trimethoprim -sulfamethoxazole, fluoroquinolones, and tetracycline antibiotics is (16%, 4.8%, 2.5%) respectively, and that amoxicillin-resistant H. influenzae<\/em> strains are susceptible to the combination of amoxicillin and clavulanic acid in 28% of cases and no resistance to C3Gs. Comparing the percentages for Qatar, Saudi Arabia and Islamic Republic of Iran, we found a high prevalence of \u03b2-lactam resistant isolates, respectively17.4% 45<\/sup> ,43,6\u00a0%46<\/sup>, 34\u00a0% 47<\/sup> and 35,7\u00a0% 48<\/sup> and two studies conducted in Rabat and Fes in (2016-2018), it was noted that no antibiotic resistance was documented. Indeed, resistance to ampicillin by production of \u00df-lactamases Type TEM-1 (Exceptional ROB-1) concerns nearly 35% of H. influenzae <\/em>strains in France. Decreased susceptibility by modification of the \u00df-lactam target is less frequent, reaching 8 to 10% of strains, but it can become a concern, affecting aminpenicillins and C3Gs to varying degrees, oral and injectable cephalosporins in Morocco 49<\/sup>, in France 50,51<\/sup>. in the United Kingdom and Germany 52,53<\/sup>\u00a0the antibiotic resistance is often multiple 37,54<\/sup>.<\/p>\n

H. influenzae <\/em>can develop resistance to fluoroquinolones through a typical stepwise mutation process of the primary target, DNA gyrase and topoisomerase IV, using four mutations in the GYRA genes, by C and by E. Initial treatment can also lead to GYRA mutations, with additional mutations occurring in Spain and France 55<\/sup>.<\/p>\n

For the resistance of S.aureus<\/em> in Morocco, it was found that the resistance increased significantly in 2016-2018 (Penicillin G 92%, ciprofloxacin 16.5% and erythromycin 14.6%) and in 2017-2019 the resistance to penicillin G 89.6%, ciprofloxacin 6.9% and erythromycin was not tested. In 2018 – 2019, (Penicillin G 2%, ciprofloxacin 4% and erythromycin 88%). These studies showed the percentage of resistant S.aureus<\/em>.<\/p>\n

In Ireland a study showed that 10 strains of S. aureus<\/em>, (71.42%) were resistant to penicillin G, no strain was resistant to meticillin, gentamycin, rifampicin, teicoplanin or vancomycin 56<\/sup>. In USA today, more than 95% S. aureus<\/em> is resistant to penicillin. Additionally, ampicillin and anti-pseudomonal penicillins 57<\/sup>.<\/p>\n

The recommended treatment is generally betalactam (aminpenicillin or penicillin G) or a macrolide in case of allergy to penicillin in France, and in Belgium 58<\/sup>, in Canada It is noted that the incidence rate of S. aureus<\/em> strains has gradually increased from 4.0% prior to 2000 to 5.2% in 2010-2020. It appears that this increasing rate is directly related to the increase in S. aureus infections and a change in antibiotic.59<\/sup>. In China, very low rates of resistance to penicillin G have been noted (11%) 60<\/sup>.<\/p>\n

The results of meta-analysis on the evolution of the resistance of S. pneumoniae, N. meningitidis, H. influenzae, <\/em>and S. aureus<\/em> on the latest Moroccan national studies have shown the need for the implementation of a strategy national report on antibiotic resistant bacteria and that an effective plan is needed to combat this resistance.<\/p>\n

Conclusion<\/strong><\/p>\n

This meta-analysis on the studies and researches on bacterial resistance to antibiotics in the last ten years in Morocco, described the incidence and the evolution of bacterial resistance of very frequent germs such as S. pneumoniae, N. meningitidis, H. influenzae and S. aureus<\/em> reported between \u00a02011-2020. It can be concluded that for the bacteria that we were interested in, the percentage of resistance varies for each species and that the incidence of resistance increases with the years. This increase has been attributed to several factors, include economic factors and socio-cultural, without neglecting role of antibiotic consumption, which has been amply demonstrated to fight against this resistance it is necessary to respect systematic surveillance measures, a good management the use of antibiotic as well as to respect rules and health protocol.<\/p>\n

Competing interests<\/strong><\/p>\n

Authors declare that they have no competing interests. The views expressed in this paper are those of the authors and do not represent the official views of their organizations.<\/p>\n

Funding Sources<\/strong><\/p>\n

This study did not receive any funding.<\/p>\n

References<\/strong><\/p>\n

    \n
  1. OMS, \u201cOrganisation Mondiale de la Sant\u00e9, Premier rapport de l\u2019OMS sur la r\u00e9sistance aux antibiotiques: une menace grave d\u2019ampleur mondiale 2014. Disponible sur: (http:\/\/www.who.int\/mediacentre\/news\/releases\/2014\/amr-report\/fr\/,\u201d OMS 2014.<\/li>\n
  2. Abduladeem G. M. Al-Selwi and Amina. Barkat, \u201cAntibiotic prescription in Morocco, national data: Meta-analysis,\u201d Pharm. Negat. Results<\/em>, vol. 13, no. 4, pp. 1074\u20131082, Nov. 2022, doi: 10.47750\/pnr.2022.13.04.148.<\/li>\n
  3. Ousaid, J. Akrim, and Y. Khayati, \u201cOveruse of antibiotics as a key driver to antibiotic resistance in Morocco: A short review with potential solutions,\u201d Int. Arab. J. Antimicrob. Agents<\/em>, vol. 10, no. 1, Art. no. 1, May 2020, doi: 10.3823\/843.<\/li>\n
  4. Haskouri S, \u201cr\u00e9sistance aux antibiotiques\u202f: m\u00e9canismes et \u00e9volution.,\u201d universit\u00e9 mohammed V facult\u00e9 de m\u00e9decine et de pharmacie de rabat, 2002.<\/li>\n
  5. Weiss K, \u201cla r\u00e9sistance bact\u00e9rienne la nouvelle guerre froide,\u201d M\u00e9decin Qu\u00e9.<\/em>, vol. 37, n\u00b0 3, pp. 41\u201349, 2002.<\/li>\n
  6. A. Sa\u00efd, \u201cEvolution de la r\u00e9sistance bact\u00e9rienne aux antibiotiques et conseils en antibioth\u00e9rapie,\u201d universit\u00e9 mohammed V facult\u00e9 de m\u00e9decine et de pharmacie de rabat, 2016.<\/li>\n
  7. Sekhsokh Yassine, \u201cR\u00e9sistance des bact\u00e9ries aux antibiotiques dans le milieu extrahospitalier dans la ville de Kenitra.Theses:142. universit\u00e9 Mohammed V facult\u00e9 de m\u00e9decine et de pharmacie de rabat,\u201d 2017.<\/li>\n
  8. M. . Morens, J. K. Taubenberger, and A. S. Fauci, \u201cPredominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness,\u201d J. Infect. Dis.<\/em>, vol. 198, no. 7, pp. 962\u2013970, Oct. 2008, doi: 10.1086\/591708.<\/li>\n
  9. Kayemba\u2010Kay\u2019s, A. M. Badran, C. Lagneaux, T. Kovacs, and A. Heron, \u201cStreptococcus pneumoniae serotype 19A meningitis in well\u2010vaccinated immunocompetent 13\u2010month\u2010old child: a case of PCV13 failure,\u201d Clin. Case Rep.<\/em>, vol. 4, no. 11, pp. 1023\u20131025, Sep. 2016, doi: 10.1002\/ccr3.660.<\/li>\n
  10. Lapeyssonnie and W. H. Organization, \u201cLa m\u00e9ningite c\u00e9r\u00e9brospinale en Afrique,\u201d Bull. World Health Organ. V 28 Suppl.<\/em>, 1963, Accessed: Nov. 06, 2021. [Online]. Available: https:\/\/apps.who.int\/iris\/handle\/10665\/72037<\/li>\n
  11. Erickson and P. De Wals, \u201cComplications and sequelae of meningococcal disease in Quebec, Canada, 1990-1994,\u201d Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am.<\/em>, vol. 26, no. 5, pp. 1159\u20131164, May 1998, doi: 10.1086\/520303.<\/li>\n
  12. P. Rubach et al.<\/em>, \u201cIncreasing Incidence of Invasive Haemophilus influenzae Disease in Adults, Utah, USA – Volume 17, Number 9\u2014September 2011 – Emerging Infectious Diseases journal – CDC,\u201d 2011, doi: 10.3201\/eid1709.101991.<\/li>\n
  13. E. Shope, \u201cSWINE INFLUENZA\u202f: III. FILTRATION EXPERIMENTS AND ETIOLOGY,\u201d J. Exp. Med.<\/em>, vol. 54, no. 3, pp. 373\u2013385, Jul. 1931, doi: 10.1084\/jem.54.3.373.<\/li>\n
  14. Dabernat H, \u201cDonn\u00e9es \u00e9pid\u00e9miologiques de la r\u00e9sistance aux antibiotiques des Haemophilus, m\u00e9ningocoques, Listeria.,\u201d Mdd Mal Infect<\/em>, no. 32, pp. 299\u2013306, 2002.<\/li>\n
  15. \u00a0Y. Liu et al.<\/em>, \u201cStaphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity,\u201d J. Exp. Med.<\/em>, vol. 202, no. 2, pp. 209\u2013215, Jul. 2005, doi: 10.1084\/jem.20050846.<\/li>\n
  16. Goldstein FW, Pan Y, and Gertner J, \u201cResistance to ceftriaxone and other beta-lactams in bacteria isolated in the community. The Vigil\u2019Roc Study Group – PubMed,\u201d 1995. https:\/\/pubmed.ncbi.nlm.nih.gov\/8585736\/ (accessed May 22, 2021).<\/li>\n
  17. Aboya Moroh J-L, \u201cR\u00e9sistance bact\u00e9rienne et phytomol\u00e9cules antimicrobiennes issues de Morinda morindoides. Agricultural sciences. Universit\u00e9 de Bretagne occidentale \u2013 Brest,\u201d Universit\u00e9 F\u00e9lix Houphou\u00ebt- Boigny, French, 2013.<\/li>\n
  18. Henriet and D. Guillemot, \u201cPharmaco-\u00e9pid\u00e9miologie des r\u00e9sistances, consommation des antibiotiques,\u201d M\u00e9decine Mal. <\/em>Infect.<\/em>, vol. 30, pp. s160\u2013s163, May 2000, doi: 10.1016\/S0399-077X(00)89084-8.<\/li>\n
  19. Moher, A. Liberati, J. Tetzlaff, D. G. Altman, and PRISMA Group, \u201cPreferred reporting items for systematic reviews and meta-analyses: the PRISMA statement,\u201d Int. J. Surg. <\/em>Lond. Engl.<\/em>, vol. 8, no. 5, pp. 336\u2013341, 2010, doi: 10.1016\/j.ijsu.2010.02.007.<\/li>\n
  20. Bouskraoui et al.<\/em>, \u201c\u00c9tude du portage rhinopharyng\u00e9 de Streptococcus pneumoniae et de sa sensibilit\u00e9 aux antibiotiques chez les enfants en bonne sant\u00e9 \u00e2g\u00e9s de moins de 2 ans dans la r\u00e9gion de Marrakech (Maroc),\u201d Arch. <\/em>P\u00e9diatrie<\/em>, vol. 18, no. 12, pp. 1265\u20131270, 2011.<\/li>\n
  21. Mdaghri, N. Jilali, H. Belabbes, Z. Jouhadi, M. Lahssoune, and S. Zaid, \u201cEpidemiological profile of invasive bacterial diseases in children in Casablanca, Morocco: Antimicrobial susceptibilities and serotype distribution,\u201d East. Mediterr. Health J. Rev. Sant\u00e9 M\u00e9diterran\u00e9e Orient. Al-Majallah Al-\u1e62i\u1e25\u1e25\u012byah Li-Sharq Al-Mutawassi\u1e6d<\/em>, vol. 18, pp. 1097\u2013101, Nov. 2012, doi: 10.26719\/2012.18.11.1097.<\/li>\n
  22. Benbachir, N. Elmdaghri, H. Belabbes, G. Haddioui, H. Benzaid, and B. Zaki, \u201cEleven-year surveillance of antibiotic resistance in Streptococcus pneumoniae in Casablanca (Morocco),\u201d Microb. Drug Resist.<\/em>, vol. 18, no. 2, pp. 157\u2013160, 2012.<\/li>\n
  23. Diawara et al.<\/em>, \u201cPhenotypic and genotypic characterization of Streptococcus pneumoniae resistant to macrolide in Casablanca, Morocco,\u201d Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis.<\/em>, vol. 40, pp. 200\u2013204, Jun. 2016, doi: 10.1016\/j.meegid.2016.03.003.<\/li>\n
  24. \u00a0Diawara et al.<\/em>, \u201cMolecular characterization of penicillin non-susceptible Streptococcus pneumoniae isolated before and after pneumococcal conjugate vaccine implementation in Casablanca, Morocco,\u201d Ann. <\/em>Clin. Microbiol. Antimicrob.<\/em>, vol. 16, no. 1, p. 23, Dec. 2017, doi: 10.1186\/s12941-017-0200-6.<\/li>\n
  25. \u00a0Ghita Y, Rajae, and Mustapha M, \u201c\u00c9pid\u00e9miologie et \u00e9valuation de la sensibilit\u00e9 des souches d\u2019Haemophilus influenzae isol\u00e9es d\u2019infections des voies respiratoires basses,\u201d J. Innov. Appl. Stud.<\/em>, vol. 20, no. 2028\u20139324, pp. 787\u2013791, 2017.<\/li>\n
  26. MOUMNI M B, YAHYAOUI G, and MAHMOUD M, \u201cMENINGITES PURULENTES EN MILIEU PEDIATRIQUE\u202f: EXPERIENCE DU LABORATOIRE CENTRAL DU CHU HASSAN II DE FES,\u201d Soci\u00e9t\u00e9 Marocaine Microbiol. M\u00e9dicale<\/em>, 2016.<\/li>\n
  27. L Amin G et al.<\/em>, \u201cProfil Epidemiologique des meningites bacteriennes,\u201d Soci\u00e9t\u00e9 Marocaine Microbiol. M\u00e9dicale<\/em>, p. P045, 2019.<\/li>\n
  28. Rhars A et al.<\/em>, \u201cEpidemiologie bacterienne des infections des parties molles,\u201d Soci\u00e9t\u00e9 Marocaine Microbiol M\u00e9dicale<\/em>, p. 11, 2019.<\/li>\n
  29. Kouara S, Filali M, Samouche M, Yahyaoui G, and Mahmoud M, \u201cProfil Bact\u00e9riologique des infections a Staphylocuccus aureus en milieu p\u00e9diatrique au chu de f\u00e8,\u201d Soci\u00e9t\u00e9 Marocaine Microbiol. M\u00e9dicale<\/em>, p. P067, 2019.<\/li>\n
  30. Nzoyikorera N et al.<\/em>, \u201cEpidemiologie des infections invasives a streptococcus pneumoniae chez l\u2019adulte a casablanca entre 2016-2018,\u201d Soci\u00e9t\u00e9 Marocaine Microbiol. M\u00e9dicale<\/em>, p. P076, 2019.<\/li>\n
  31. Raghani A et al.<\/em>, \u201cEpidemiologie bacterienne des pneumopathies\u202f: etude retrospective sur 7 ans,\u201d Soci\u00e9t\u00e9 Marocaine Microbiol. M\u00e9dicale<\/em>, p. P079Bis, 2019.<\/li>\n
  32. Saoud M Z et al.<\/em>, \u201cInfections profondes a staphylococcus aureus\u202f: \u00e0 propos de 117 cas,\u201d Soci\u00e9t\u00e9 Marocaine Microbiol. M\u00e9dicale<\/em>, p. P086, 2019.<\/li>\n
  33. Ait Mouss et al.<\/em>, \u201cEpidemiological profile of Neisseria meningitidis in Casablanca, Morocco: 2010-2019,\u201d Access Microbiol.<\/em>, vol. 2, no. 9, p. acmi000157, 2020, doi: 10.1099\/acmi.0.000157.<\/li>\n
  34. \u00a0A. Moghnieh, Z. A. Kanafani, H. Z. Tabaja, S. L. Sharara, L. S. Awad, and S. S. Kanj, \u201cEpidemiology of common resistant bacterial pathogens in the countries of the Arab League,\u201d Lancet Infect. Dis.<\/em>, vol. 18, no. 12, pp. e379\u2013e394, Dec. 2018, doi: 10.1016\/S1473-3099(18)30414-6.<\/li>\n
  35. A. Michael, D. Dominey-Howes, and M. Labbate, \u201cThe Antimicrobial Resistance Crisis: Causes, Consequences, and Management,\u201d Front. Public Health<\/em>, vol. 2, Sep. 2014, doi: 10.3389\/fpubh.2014.00145.<\/li>\n
  36. Brian H. Harcourt et al.<\/em>, \u201cPopulation-Based Surveillance of Neisseria meningitidis Antimicrobial Resistance in the United States,\u201d Open Forum Infect. Dis.<\/em>, vol. 2, no. 3, 2015, doi: https:\/\/doi.org\/10.1093\/ofid\/ofv117.<\/li>\n
  37. Fenoll, I. Jado, D. Vicioso, A. P\u00e9rez, and J. Casal, \u201cEvolution of Streptococcus pneumoniaeSerotypes and Antibiotic Resistance in Spain: Update (1990 to 1996),\u201d J. Clin. <\/em>Microbiol.<\/em>, vol. 36, no. 12, pp. 3447\u20133454, Dec. 1998, doi: 10.1128\/JCM.36.12.3447-3454.1998.<\/li>\n
  38. SBIMC, \u201cRecommandations de traitements anti-infectieux en milieu hospitalier.\u201d<\/li>\n
  39. Bertrand, F. Carion, R. Wintjens, V. Mathys, and R. Vanhoof, \u201cEvolutionary changes in antimicrobial resistance of invasive Neisseria meningitidis isolates in Belgium from 2000 to 2010: increasing prevalence of penicillin nonsusceptibility,\u201d Antimicrob. Agents Chemother.<\/em>, vol. 56, no. 5, pp. 2268\u20132272, May 2012, doi: 10.1128\/AAC.06310-11.<\/li>\n
  40. E. Rosenstein, S. A. Stocker, T. Popovic, F. C. Tenover, and B. A. Perkins, \u201cAntimicrobial resistance of Neisseria meningitidis in the United States, 1997. The Active Bacterial Core Surveillance (ABCs) Team,\u201d Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am.<\/em>, vol. 30, no. 1, pp. 212\u2013213, Jan. 2000, doi: 10.1086\/313599.<\/li>\n
  41. Muhamed-Kheir Taha, Julio A V\u00e1zquez, Eva Hong, Desiree E Bennett, and Sophie Bertrand, \u201cTarget gene sequencing to characterize the penicillin G susceptibility of Neisseria meningitidis,\u201d Antimicrob Agents Chemother<\/em>, vol. 51, no. 8, pp. 2784\u201392, 2007, doi: doi: 10.1128\/AAC.00412-07.<\/li>\n
  42. Merijn W Bijlsma, Vincent Bekker, Matthijs C Brouwer, Lodewijk Spanjaard, Diederik van de Beek, and Arie van der Ende, \u201cEpidemiology of invasive meningococcal disease in the Netherlands, 1960-2012: an analysis of national surveillance data,\u201d Lancet Infect Dis<\/em>, vol. 14, no. 9, pp. 805\u201312, 2014, doi: doi: 10.1016\/S1473-3099(14)70806-0.<\/li>\n
  43. Willerton et al.<\/em>, \u201cIncrease in penicillin-resistant invasive meningococcal serogroup W ST-11 complex isolates in England,\u201d Vaccine<\/em>, vol. 39, no. 19, pp. 2719\u20132729, May 2021, doi: 10.1016\/j.vaccine.2021.03.002.<\/li>\n
  44. Cavallo JD, Nicolas P, and Martet G, \u201cActualit\u00e9s sur la sensibilit\u00e9 de Neisseria meningitidis aux antibiotiques et en particulier aux b\u00eatalactamines. La Lettre de l\u2019Infectiologue.,\u201d Tome XIII<\/em>, vol. 9, pp. 429\u2013433, 1998.<\/li>\n
  45. Kassaa, M. Hamze, F. Dabboussi, H. Mallat, M. Achkar, and S. Hlais, \u201cPrevalence of type b Haemophilus influenzae and antibiotic resistance in 52 clinical isolates in north Lebanon,\u201d East. Mediterr. Health J. Rev. Sant\u00e9 M\u00e9diterran\u00e9e Orient.<\/em>, vol. 19, p. 108, 2013.<\/li>\n
  46. Mojgani, M. Rahbar, M. Taqizadeh, M. P. Ashtiani, and M. Mohammadzadeh, \u201cBiotyping, capsular typing, and antibiotic resistance pattern of Haemophilus influenzae strains in Iran,\u201d Jpn. J. Infect. Dis.<\/em>, vol. 64, no. 1, pp. 66\u201368, 2011.<\/li>\n
  47. Al-Binali and S. Al-Fifi, \u201cProfile of childhood meningitis in a hospital in South West Saudi Arabia.,\u201d Saudi Med. J.<\/em>, 2002.<\/li>\n
  48. F. Elsaid et al.<\/em>, \u201cClinical presentation of acute bacterial meningitis in Qatar,\u201d Neurosci. Riyadh Saudi Arab.<\/em>, vol. 7, no. 4, pp. 266\u2013271, Oct. 2002.<\/li>\n
  49. Dabernat H., \u201cHaemophilus influenzae. (Centre national de r\u00e9f\u00e9rence des Haemophilus influenzae). Surveillance nationale des maladies infectieuses 1998\u20132000. Saint-Maurice,\u201d Veille- Sanit.<\/em>, pp. 91\u20135, 2000.<\/li>\n
  50. Dabernat, M. Seguy, G. Faucon, and C. Delmas, \u201c\u00c9pid\u00e9miologie et \u00e9valuation de la sensibilit\u00e9 aux antibiotiques de souches d\u2019Haemophilus influenzae isol\u00e9es en 2004 en France,\u201d 2007, doi: 10.1016\/J.MEDMAL.2006.10.014.<\/li>\n
  51. Masson, \u201cActivit\u00e9 de 9 -lactamines sur 280 souches d\u2019Haemophilus influenzae<\/em> r\u00e9sistantes \u00e0 l\u2019ampicilline par b\u00eatalactamase et m\u00e9canisme non enzymatique,\u201d EM-Consulte<\/em>, 2022. https:\/\/www.em-consulte.com\/article\/164351\/activite-de-9-lactamines-sur-280-souches-d-haemoph (accessed Apr. 26, 2022).<\/li>\n
  52. Ball et al.<\/em>, \u201cAntibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence,\u201d J. Antimicrob. Chemother.<\/em>, vol. 49, no. 1, pp. 31\u201340, Jan. 2002, doi: 10.1093\/jac\/49.1.31.<\/li>\n
  53. Lode and M. Allewelt, \u201cRole of newer fluoroquinolones in lower respiratory tract infections,\u201d J. Antimicrob. Chemother.<\/em>, vol. 49, no. 5, pp. 709\u2013712, May 2002, doi: 10.1093\/jac\/dkf024.<\/li>\n
  54. \u00a0A. Needham, \u201cHaemophilus influenzae: antibiotic susceptibility.,\u201d Clin. Microbiol. Rev.<\/em>, vol. 1, no. 2, pp. 218\u2013227, Apr. 1988.<\/li>\n
  55. Teresa Bastida et al.<\/em>, \u201cLevofloxacin treatment failure in Haemophilus influenzae pneumonia – PubMed,\u201d 2003. https:\/\/pubmed.ncbi.nlm.nih.gov\/14718097\/ (accessed Apr. 07, 2022).<\/li>\n
  56. Maleb, M. Frikh, Y. B. Lahlou, B. Belefquih, A. Lemnouer, and M. Elouennass, \u201c\u00c9coulements vaginaux d\u2019origine infectieuse chez la femme adulte \u00e0 l\u2019h\u00f4pital militaire d\u2019instruction Mohammed V de Rabat (Maroc)\u00a0: \u00e9tude de 412\u00a0cas,\u201d Rev. Sage-Femme<\/em>, vol. 17, no. 3, pp. 122\u2013126, Jun. 2018, doi: 10.1016\/j.sagf.2018.03.004.<\/li>\n
  57. \u00a0J. Foster, \u201cAntibiotic resistance in Staphylococcus aureus. Current status and future prospects,\u201d FEMS Microbiol. <\/em>Rev.<\/em>, vol. 41, no. 3, pp. 430\u2013449, May 2017, doi: 10.1093\/femsre\/fux007.<\/li>\n
  58. Bergogne-B, \u201cFlores vaginales normales, vaginites et vaginoses bact\u00e9riennes\u202f: diagnostic et th\u00e9rapeutique,\u201d Flores Vaginales Norm. <\/em>Vaginites Vaginoses Bact\u00e9riennes Diagn. Th\u00e9rapeutique<\/em>, vol. 9, no. 2, pp. 139\u2013144, 2007.<\/li>\n
  59. Castanheira, A. A. Watters, R. E. Mendes, D. J. Farrell, and R. N. Jones, \u201cOccurrence and molecular characterization of fusidic acid resistance mechanisms among Staphylococcus spp. from European countries (2008),\u201d J. Antimicrob. Chemother.<\/em>, vol. 65, no. 7, pp. 1353\u20131358, Jul. 2010, doi: 10.1093\/jac\/dkq094.<\/li>\n
  60. \u00a0Jeffery Ho, Maureen V Boost, and Margaret M O\u2019Donoghue, \u201cTracking sources of Staphylococcus aureus hand contamination in food handlers by spa typing – PubMed,\u201d 2015. https:\/\/pubmed.ncbi.nlm.nih.gov\/25997877\/ (accessed Apr. 09, 2022).<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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