Sci-AfricJournalofScientificIssues,ResearchandEssaysVol.2(10),Pp.456-461,October,2014. (ISSN2311-6188)
ResearchPaper
Community-AcquiredPneumoniaCausedByHaemophilusInfluenzaeinaGroupof Non-VaccinatedAdultPopulationinEgypt.
MonaEmbarekMohamed1,MohamedA.El-MokhtarMahmoud1,AlaaThabetHassan2
1.DepartmentofMicrobiologyandImmunology, FacultyofMedicine,AssiutUniversity,Assiut, Egypt.
2.DepartmentofChestDiseases,FacultyofMedicine, AssiutUniversity, Assiut,Egypt.
Author’sE-mail:ccepted October24th,2014
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ABSTRACT
Community-acquiredpneumoniaisacommondiseaseandafrequentcauseofmorbidityandmortalityworldwide.HaemophilusinfluenzaeisaleadingcauseofCAP.ThecurrentstudywasconductedtodeterminetheserotypedistributionandantimicrobialsusceptibilitypatternsofHaemophilusinfluenzaeisolatedfromunvaccinatedadultpatientswithCAPat Assiut UniversityHospitals.MaterialsandMethods:FromSeptember2013toaugust2014,sputumsamplesfrom132adultpatientswithCAPwereanalyzedforthedetectionofHaemophilusinfluenzausingconventionalmethods.AntimicrobialsusceptibilityandserotypingofHaemophilusinfluenzaewasperformed.Results:Haemophilusinfluenzaeweredetectedin21(16%)CAP-patients.Non-typeableHinfluenzaewerethemostfrequentlyisolatedserotypethatfoundin15(71%)ofHinfluenzae-cases.Hinfluenzaetypebwasfoundin5(24%)cases.WhileHinfluenzaetypefwasfoundinone(5%)case.CasesweredetectedmainlyduringJanuary,February,andMarch.ResistancewashighestfortheB-lactamgroupofantibiotics.Conclusion:CAPhasadiseaseburdeninadultpatientsatAssiutUniversityHospitals,Egypt.HinfluenzaeisaleadingcauseofCAPwhichwasassociatedmostlywithnon-typeableserotypes.ResistancetopenicillinandotherantimicrobialagentsincreasedrapidlyduringthelastyearsamongH influenzaestrains.
Keywords:Haemophilusinfluenzae,community-acquiredpneumonia,serotyping, antimicrobialresistance.
INTRODUCTION
Community-acquiredpneumonia(CAP)wasdefinedaspneumoniaacquiredoutsidethehospitalsetting[1].Itisoneofthemostcommonacuteinfectionsrequiringadmissiontohospital.RiskfactorsforCAPincludeage,smoking,andco-morbidities[2].TheannualincidenceofCAPvariesfrom5–11per1,000populationwithhigherratesintheelderly[3].Haemophilusinfluenzae(H.influenzae)isoneofthecommoncausesofcommunity-acquiredlowerrespiratorytract(LRT)infectionsparticularlyCAPandinvasivedisease[4].Onthebasisoftheantigenicproperties,sixserotypesofencapsulatedH.influenzaearedistinguished(a,b,c,d,e,andf),andtherearealsononencapsulatedornon-typeableH.influenzae(NTHi)[5].Nowadays,non-typeableisolates(NTHi)account forthemajorityofLRTIaftertheintroductionofHib conjugatevaccines[6].Amainproblemisthat,CAP iscausedbydrug-resistantHinfluenzaestrains.Althoughbeta-lactams(aspenicillin)haslongbeenthemainstayoftreatmentofH.influenzaeinfections,strainswithdecreasedsusceptibilitytopenicillinhave becomeincreasinglyprevalentandarenow aseriousproblemworldwide[7].Therefore,periodicmonitoringofthepatternsofantimicrobialresistanceisnecessarytoguideeffectivetreatmentagainstHinfluenzae[8].TheincidenceofCAPanditscommoncomplications,suchastherequirementforintensivecareandcomplicatedpara-pneumoniceffusions,areincreasing,makingitessentialforallphysicianstohaveagoodunderstandingofthemanagementofCAP[1].
MATERIALSANDMETHODS
Studydesign
ThisisaprospectivestudythatcarriedoutatAssiutUniversityHospitals,Assiut, Egyptover12-monthsperiodfromSeptember2013toendAugust2014;aimingtodeterminetheserotypedistributionandantimicrobialsusceptibilityprofileofH.influenzaestrainscausingCAPamongagroupofadultpopulationunvaccinatedto H.influenzae.ThestudywasapprovedbythemedicalethicalcommitteeattheFacultyofMedicine,AssiutUniversity,andoralconsentsweretakenfromallsubjectspriortosamplecollection.
Studypopulation
Un-vaccinatedadultswithcommunity-acquiredpneumoniawhoattendedtheChestDepartmentwereeligibleforthestudy.Provedtuberculosispatientsandpatientswhowerereceivingantibioticswereexcludedfromthestudy.Pneumoniawasdefinedbysignsandsymptomssuggestiveoflowerrespiratorytractinfectiontogetherwithchestradiographicfindingsconsistentwithpneumoniaasdeterminedinitiallybytheclinicalphysician.
Questionnaires were fulfilledthatincludeddemographicandclinicaldata;age, gender,occupation,symptoms,admission,andassociatedriskfactors(e.g.smoking,immunosuppressivecondition,associatedcardiopulmonaryorsystematicco-morbidities).Smokinghistorywascalculatedasnumberofpack/year=numberofcigarettessmokedperday×numberofyearssmoked/20(1packhas20cigarettes)[9].Patientsunderwentthoroughclinicalexamination, chest x-ray,andpulmonaryfunctiontests.
Samplecollection
Sampleswereobtainedwithin24hoursafterthepatient´sadmissiontoensurecommunity-acquiredinfection.Validsputumsampleswerecollectedfrom132patientswithCAPthrougheffectivecoughingtoobtainlungsecretionsasdescribedpreviously[10].Frothysalivaandsecretionsfrompharynxwerediscardedandthepatientwasaskedtoproduceanotherspecimen.Sampleswerecollectedintowide-mouthedsterilescrew-cappedcupsthatcontainedbrainheartinfusionglycerolbrothasatransportmediumandtransportedtothelaboratoryattheMicrobiologyandImmunologyDepartment,FacultyofMedicine,AssiutUniversitywherebacteriologicaldiagnosiswasperformed.
IdentificationofH.influenzaestrains
Samples wereexaminedmicroscopicallyafterstainingwithGram´sstainandculturedonchocolateagar.Theagarplateswereincubatedaerobicallyat35–36°Cwith5%CO2for24-48hours.Thevalidsputumculturedefinedasthathadquantitativeculture
≥105colonyformingunits(CFU)/ml[11].Haemophilusinfluenzaeisolateswereidentifiedbasedoncolonialmorphology,Gram
staining,andstandardbiochemicalreactionsaccordingtotheBergey'sManualofSystematicBacteriology[12].
Serotyping ofH.influenzaestrains
SerotypingwasperformedbyHaemophilusinfluenzaeagglutinationkitcontaining6poolantisera(a-f)(Difco,USA)accordingto manufacturer´sinstructions.Briefly,a loopfulofgrowthoftheorganismismixed with a dropoftheantiserumonanagglutinationslide,mixedthoroughlyandinspectedforagglutinationwithinoneminute.
Antibioticsusceptibilitytesting
ThesusceptibilitypatternsofH.influenzaeisolatestopenicillin,amoxicillin,amoxicillin/clavulanicacid,trimethoprim-sulfamethoxazole,clarithromycin,azithromycin,chloramphenicol,ceftriaxone,ciprofloxacin,levofloxacin,meropenem,andimipenem(Bioanalyse,Turkey)weredetermined.ThetestwasperformedusingthediskdiffusionmethodonMullerHintonchocolateagarasrecommendedbytheClinicalandLaboratoryStandardsInstitute(CLSI)guidelines[13].Theresultswereinterpretedassusceptible(S),intermediate(I),orresistant(R).Multidrug-resistant(MDR)Hinfluenzaewasdefinedasacquirednon-susceptibilitytoat leastoneagentinthreeormoreantimicrobialcategories[14].
Statisticalanalysis
TheSPSSprogramversion19.0wasusedforthestatisticalanalysisofdata.Datawerepresentedasmeanandstandarddeviationornumberandpercentageasappropriate.TheX2testwasusedtoanalyzecategoricalvariablesandaPvalue˂0.05wasconsideredstatisticallysignificant.
RESULTS
Studypopulation
FromSeptember2013toAugust2014,atotalof132adultpatients(89malesand43females)mostly(74%)wereresidentsofAssiutProvincewithcommunity-acquiredpneumoniawereprospectivelyenrolledinthisstudy.Most(65%)patientswereadmittedattheChestdepartment(Table1).Themean ageofpatientsranged from28-72years(mean±SD;44.3±27.5years).Thirtyeight(29%)patients were heavysmokers(P<0.01),19(14%)patients wereex-smokers,14(11%)patients weremoderatesmokers,and12(9%)patients were mild smokers.Allfemales(43)enrolledinthestudyinadditionto sixmales werenon-smokers(Table1).
Ofthe132patients,lobarpneumoniawasthemostdetectedanatomicaltypein75(57%)patients(P<0.005),49(37%)patientshadbronchpneumonia,3(2.3%)patientshadmultilobarpneumonia,andonepatient(0.8%)hadinterstitialpneumonia.Three(2.3%)patientssufferedfrompleuraleffusionandonepatient(0.8%)showed cavitation(Table1).
Table1:DemographicandclinicalcharacteristicsofCAPpatients(n=132)
Patients’characteristics / N (%)Sex
Female / 43(33)
Male
Geographicalarea / 89(67)
Assiut / 98(74)
Qena / 15(11)
Sohag / 10(7.6)
NewValley / 5 (4)
Aswan / 4 (3)
Siteofadmission
Chestdepartment / 86(65)
Chestintensivecareunit / 46(35)
Smokingindex
0 (non-smoker) / 49(37)
Ex-smoker / 19(14)
20(mildsmoker) / 12(9)
20-30(moderatesmoker) / 14(11)
>30 (heavysmoker) / 38(29)
Radiographicfindings
Lobar75(57)
Bronchopneumonia49(37)
Interstitial1 (0.8)
132patients
Multilobarpneumonia3 (2.3)
Cavitation1 (0.8)
Pleuraleffusion3 (2.3)
Abbreviations:CAP=community-acquiredpneumonia
Characteristics ofHinfluenzaeserotypes
Atotalof21H influenzaestrainsweredetected.Non-typeableH influenzae (NTHi)werethemostfrequentlyisolatedserotypethatfoundin15(71%)ofHinfluenzae-cases.Hinfluenzaetypebwasfoundin5(24%)cases.WhileHinfluenzaetypef(Hif)were found inone(5%)case(Fig1).
Characteristics ofHinfluenzaecases
Hinfluenzaeweredetectedin21(16%)CAPpatients.CasesweredetectedmainlyduringJanuary,February,andMarch(19%each),duringDecemberandMay(14%each),November, April,andDecember(5%each)(Figure1).
Figure1:SeasonaldistributionofHinfluenzaestrainsincasesofCAP
Abbreviations:CAP=community-acquiredpneumonia;Hib=Hinfluenzaetypeb;Hif=Hinfluenzaetypef;NTHi=nontypable Hinfluenzae
Seventeen(81%)patientsweremalesand4(19%)werefemaleswithagerangedbetween29-72years(mean±SD;48.6±
11.8years).Most(67%)H.influenzae-caseswereadmittedtotheChestdepartment.Six(28.5%)ofHinfluenzae-casesweremoderatesmokers,5cases(24%)wereheavysmokers,5cases(24%)werenonsmokers,fourcases(19%)weremildsmokers,whileonecase(4.5%)wasex-smokerthathad a previoussmokingindexof27(Table2).Themost(62%)anatomicalpneumonic-typesignificantlyassociatedwithH.influenzaeinfectionwasbronchopneumoniathatwasdetectedin13patients.Lobarpneumonia,werefoundin6(28%)patients,bothofinterstitialpneumoniaandmultilobarpneumoniaweredetectedinone(5%)patienteach(Table2).
TenH.influenzae-cases(48%)sufferedfromassociatedcardiopulmonaryconditions.Respiratoryfailure(RF)wasfoundin2(9.5%)patients.Lungcancer,DCP,lungcollapse,respiratoryfailure,pleuraleffusion,cardiacischemia,cardiomyopathy,pulmonaryembolism,pulmonarycavitation,andhydropneumothoraxwerefound inone(5%)caseeach.Four(19%)patients weremechanicallyventilated.Othersystematicco-morbiditiesasdiabetesmellitus(DM),hypertension,renalimpairment,anddeepvenousthrombosis(DVT)weredetectedin 5 (24%)cases(Table 2).
Table2:ClinicalcharacteristicsofH.influenzaepneumonia(no=21)
Patient / Age / Gender / Residence / Siteofadmission / Smokingindex / Underlying disease(bronchopulmonarycondition-immunosuppression) / Radiological findings
1 / 72
y / M / NewValley / ChestDepart. / 8 / Rightlungcancer / Ltlowerlobepneumonia
2 / 66
y / M / Assiut / ChestICU / 32 / DCP,MV / Bronchopneumonia
3 / 53
y / M / Assiut / ChestDepart. / 25 / none / Bronchopneumonia
4 / 41
y / M / Assiut / ChestDepart. / 21 / DM,hypertension / Ltlowerlobepneumonia
5 / 35
y / M / Qena / ChestICU / 0 / RF,MV / Bronchopneumonia
6 / 40
y / M / Assiut / ChestDepart. / 37 / Rtpleuraleffusionwithunderlyingcollapse / Rt lowerlobepnemonia
7 / 50
y / M / Assiut / ChestDepart. / 16 / none / Interstitialpneumonia
8 / 54
y / F / Assiut / ChestDepart. / 0 / DM,renalimpairment / Bronchopneumonia
9 / 60
y / M / Assiut / ChestDepart. / 22 / none / Bronchopneumonia
10 / 63
y / F / Sohag / ChestDepart. / 0 / none / Rtupperlobepneumonia
11 / 47
y / M / Assiut / ChestICU / Ex-smoker(previousindex27) / Cardiacischemia,massivehemoptysis,MV / Bronchopneumonia
12 / 29
y / M / Assiut / ChestDepart. / 39 / none / Bronchopneumonia
13 / 43
y / M / Assiut / ChestDepart. / 6 / none / Ltlowerlobepneumonia
14 / 55
y / M / Assiut / ChestDepart. / 32 / cardiomyopathy / Bronchopneumonia
15 / 51
y / M / Assiut / ChestICU / 30 / Pulmonaryembolism, Rt lowerlimb DVT,DM / Multilobarpneumonia
16 / 30
y / M / Aswan / ChestICU / 21 / RF,MV / Bronchopneumonia
17 / 54
y / F / Assiut / ChestDepart. / 0 / Pulmonarycavitation / Bronchopneumonia
18 / 58
y / M / Assiut / ChestDepart. / 35 / Lthydropneumothorax / Ltlowerlobepneumonia
19 / 41
y / M / Sohag / ChestDepart. / 29 / DM / Bronchopneumonia
20 / 46
y / M / Qena / ChestICU / 11 / none / Bronchopneumonia
21 / 33
y / F / Assiut / ChestICU / 0 / Lowerlimb DVT / Bronchopneumonia
Abbreviations:DCP=decompensatedCore-pulmonale;MV=mechanicalventilation;DM=diabetesmellitus;DVT=deepvenousthrombosis;F=female;ICU=Intensivecareunit;Lt=left;M=male;Rt=right;RF=respiratoryfailure.
Antimicrobialsusceptibilitypattern
ResistancetopenicillinwasthehighestinallH.influenzaeserotypes(P=0.000).Amongthe21H.influenzaeisolates,13(62%),8(38%),4(19%),3(14%),2(9.5%)strainswereresistanttotrimethoprim/sulfamethoxazole,chloramphenicol,amoxicillin,meropenem, andceftriaxone,respectively.Resistanceto amoxicillin/clavulanicacid, azithromycin, ciprofloxacin,andimipenemwasfoundinone(5%)H.influenzaestraineach.AllH.influenzaestrainsinthisstudywerefoundsensitivetoclarithromycinandlevofloxacin.NTHishowedthehighestresistancetoantibioticsversusHibandHif(P=0.01and0.001,respectively).ThreeH.influenzaestrainswere found to beMDR(Table3).
Table3:DistributionofthedetectedserotypesofH. influenzaand theirantimicrobialresistanceagainst12antimicrobials
Serotype / No(%)ofisolates / No(%)ofisolateswithindicated resistance / MultiresistantStrains(%)
P / AX / AMC / SXT / AZM / CLR / C / CIP / CRO / LEV / MER / IMP
NTHi / 15(71) / 14(93) / 2(13) / 1(7) / 10(67) / 1(7) / 0(0) / 6(47) / 1(7) / 2(13) / 0(0) / 2(13) / 1(7) / 2(13)
Hib / 5 (24) / 5(100) / 1(20) / 0(0) / 3(60) / 0(0) / 0(0) / 2(40) / 0(0) / 0(0) / 0(0) / 1(20) / 0(0) / 1(20)
Hif / 1 (5) / 1(100) / 1(100) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0)
Total / 21(100) / 20(95) / 4(19) / 1(5) / 13(62) / 1(5) / 0(0) / 8(38) / 1(5) / 2(9.5) / 0(0) / 3(14) / 1(5) / 3(14)
Abbreviations:NTHi=non-typableHinfluanzae;Hib=Hinfluenzatypeb;Hif=Hinfluenzatypef;P=penicillin;AX=amoxicillin;AMC=amoxicillin/clavulanicacid;SXT=trimethoprim/sulfamethoxazole;AZM=azithromycin;CLR=clarithromycin;C=chloramphenicol;CIP=ciprofloxacin;CRO=ceftriaxone;LEV=levofloxacin;MER=meropenem;IMP=imipenem.
DISCUSSION
Uptodate,thereisnoclearreportthatdescribestheprevalentHinfluenzaeserotypesincasesofCAP inAssiut.Thisstudydescribestheepidemiologiccharacteristics,antibioticsusceptibilitypatterns,andserotypeprevalenceofH.influenzaestrainsinunvaccinatedpatientswithCAPatAssiutUniversityHospitals,Assiut,Egypt.H.influenzaeplayacrucialroleintheetiologyofCAPasevidentinourstudy.ThisisreportedpreviouslyeitherinEgypt[15],intheArabianPeninsulalikeSaudiaArabia[16],orglobally[17,18, 19;20].
Non-typeableH.influenzae(NTHi)werethemostprominentserotypeassociatedwithCAPinthisstudyincontrasttothecapsulatedstrainsHibandHif.Thishadbeendetectedinotherstudies[21;22].ThisisexplainedbytheintroductionofHibconjugatevaccinesthatincreasedtheprevalenceofnon-capsulatedstrainsofH.influenzae[6].PrevalenceofH.influenzapneumoniawasmostlydetectedduringDecember,January,February,March,andMay.InfectionswithH.influenzae-pneumoniaoccuranytimebutmostoftenduringthewinterandearlyspringwhenrespiratoryillnessesaremorecommon[23].Inthisstudy,incidenceofpneumoniawashigherinmales(67%)thaninfemales(33%).Thisisreportedpreviously[24].Thesmokinghabitsinmalesmakethemmorepronetotheoccurrenceofpneumonia.Thepredispositionofcigarettesmokersfordevelopmentofrespiratoryinfectionscausedbymicrobialpathogensiswellrecognized[25].Smokingcigaretteshasasuppressiveeffectontheprotectivefunctionsofairwayepithelium,alveolarmacrophages,dendriticcells,naturalkiller(NK)cellsandadaptiveimmunemechanisms,inthesettingofchronicsystemicactivationofneutrophils.Cigarettesmokealsohasadirecteffectonmicrobialpathogenstopromotethelikelihoodofinfectivedisease,specificallypromotionofmicrobialvirulenceandantibioticresistance[25].About29%ofthepneumonia-casesinthestudyhadthesmokingindex>30.ApreviousmultivariateanalyseswereperformedinUSA[26]andSweden[27]documentedthatthehighsmokingindexareconsiderableriskfactorsfortheoccurrenceofpneumonia.About48%ofHinfluenzae-casesinthisstudywereassociatedwithcardiopulmonaryco-morbiditiesmostlyaffectingthelungtissue.Presenceofco-morbiditiesespeciallythoseassociatedwithreducedlungfunctionareassociatedwithhigherriskofpneumonia[24;28].Inourstudy,lobarpneumoniawasthemostcommonanatomicaltypedetectedinthe132enrolledcases.Althoughlobarpneumoniaisthemost anatomicaltypeassociatedwithCAP[29], bronchopneumoniawasreportedtobethemostanatomicaltypeofCAPthatassociatedwithH.influenzaeasevidentfromthisstudy.Foralongtime,β-lactamantimicrobialswerethefirsttherapeuticoptionfortreatingCAPduetoH.influenzae[30].Decreasedsusceptibilitiestoβ-lactamantibioticsamongallHinfluenzaeserotypesespeciallyNTHiinthisstudycouldbeexplainedbythefrequentpulmonaryco-morbiditiesfoundinthepatients´group.Hinfluenzaestrainsinthisstudyshowed,inaccordancewithotherstudies[31;32],goodresponsetoamoxicillin/clavulanicacid,third-generationcephalosporins,oxazolidinones,quinolones,andcarbapenems.Therefore,theyaregoodtherapeuticagentsfortreatmentofCAPduetoH.influenzae.AllHibstrainsinthisstudyshowedresistancetopenicillinand40%ofHibwereresistanttochloramphenicol.ThisisconsistentwithpreviousstudiesfromAfricawhereβ-Lactamaseproductionamong Hibisolatesisincreasing,asrecordedinthesereports[33].
CONCLUSION
CAPhasadiseaseburdeninadultpatientsatAssiutUniversityHospitals,Egypt.HinfluenzaeisaleadingcauseofCAPwhichwasassociatedmostlywithnon-typeableserotypes.ResistancetopenicillinandotherantimicrobialagentsincreasedrapidlyduringthelastyearsamongH influenzaestrainsinAssiutandotherProvincesinEgypt.
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