ArticlePDF Available

Antibiotics for whooping cough (pertussis)

July 2007
Cochrane Database of Systematic Reviews

July 2007

Authors:

Sultan M Altunaiji

Berlin Medical Centre

Nigel Curtis

The Royal Children's Hospital

John Massie

The Royal Children's Hospital

Content uploaded by John Massie

Content may be subject to copyright.

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Antibiotikabehandling af kighosteUgeskr Læger 2006;168(34):2802- 2805

EVIDENSBASERET MEDICIN

Stud.med. Peter Erik Pontoppidan & professor Birthe Høgh

H:S Hvidovre Hospital, Pædiatrisk Afdeling

Kighoste (pertussis, tussis convulsiva) forårsages af Bordetella

pertussis og regnes for at være den mest smitsomme bakterie-

infektion, vi har i Danmark. Kighostevaccination af spædbørn

har medført en betydelig reduktion i svær sygdom og død

hos mindre børn, men spædbørns død på grund af kighoste

forekommer stadig, specielt hos børn under tre måneder, hos

hvem der sjældent ses kigen, men apnøtilfælde og cyanose [1].

Hurtig diagnostik og behandling af kighostetilfælde for at

hindre smittespredning er vigtig.

Siden 1998 har man på Statens Serum Institut foruden

dyrkning af B. pertussis kunnet påvise bakterien med polyme-

rasekædereaktion [2]. Der anbefales makrolid antibiotika til

både profylakse og behandling [3]. Erythromycin er et almin-

deligt og udbredt valg af antibiotika ved kighoste. Desværre

har erythromycin mange bivirkninger specielt gastrointesti-

nale. Nye makrolider som clarithromycin og azithromycin

kan være et alternativ til erythromycin på grund af en bedre

bivirkningsprofil [4, 5].

Formålet med Cochrane-analysen

I den aktuelle Cochrane-analyse, Antibiotics for whooping

cough (pertussis), var formålet at undersøge fordele og bivirk-

ninger ved forskellige antibiotikaregimener i behandling af

kighoste og ved kighosteprofylakse af kontakter. Vedrørende

symptombehandling af kighoste henvises til en tidligere

Cochrane-gennemgang af Pillay 2003 [6].

Cochrane-analysens design og resultater

Cochrane-metaanalysen er baseret på en litteratursøgning

for randomiserede eller kvasirandomiserede, kontrollerede,

kliniske undersøgelser omhandlende behandling af kighoste

med antibiotika og antibiotikaprofylakse mod kighoste i

CENTRAL (2004), som også indeholder DARE. Der blev søgt

i MEDLINE (1966-2004) og EMBASE (1974-2003). Forfatterne

til Cochrane-gennemgangen har desuden søgt efter ikkepub-

licerede studier gennem eksperter, og de har taget kontakt til

forfatterne af de inkluderede studier. I perioden 1953-2002 er

der publiceret flere hundrede artikler, der omhandler antibio-

tikaanvendelse i forbindelse med kighoste, men kun 12 stu-

dier med i alt 1.720 deltagere opfyldte kriterierne for rando-

miserede eller kvasirandomiserede, kontrollerede, kliniske

undersøgelser.

Ti af de 12 undersøgelser omhandlede behandling af

kighoste og inkluderede 1.319 patienter, heraf var 1.151 børn,

og 168 var børn og voksne husstandskontakter. To under-

søgelser omhandlede antibiotikaprofylakse af husstandskon-

takter til B. pertussis-positive børn og inkluderede i alt 401

personer [7].

Antibiotikabehandling af kighoste

Klinisk effekt

Den kliniske effekt ved behandling med antibiotika er anført i

alle 12 studier. I studierne angives der dog forskellige mål for

den kliniske helbredelse/bedring. Det medfører, at det ikke

var muligt at samle resultaterne i en metaanalyse, men resul-

taterne måtte analyseres enkeltvis.

Der blev i et studie rapporteret om klinisk helbredelse hos

4-14% efter erythromycinbehandling, og i et andet studie,

hvor erythromycin blev givet i 14 dage, blev der rapporteret

om nedsat hoste på dag 14.

Mikrobiologisk eradikation

Mikrobiologisk eradikation efter antibiotikabehandling vari-

erede fra 0 til 100% i ni undersøgelser, der inkluderede i alt 610

patienter. Metaanalyse var ikke mulig, da der blev brugt for-

skellige typer af antibiotika. I et studie af erythromycin var

der negativ B. pertussis-dyrkning på syvende behandlingsdag

hos ni ud af ti patienter, hvorimod alle i den ubehandlede

gruppe stadig var B. pertussis-positive på syvendedagen.

Mikrobiologisk tilbagefald

Mikrobiologisk tilbagefald, defineret som positiv B. pertussis-

podning en uge efter ophør med antibiotika forudgået af en

negativ podning, blev rapporteret hos en ud af 72 (1,4%) i

gruppen, der blev behandlet med erythromycinestolat (i syv

dage) og hos 0 ud af 83 (0%) i gruppen, der blev behandlet

med erythromycinestolat (i 14 dage).

Komplikationer

Luftvejskomplikationer (bronkopneumoni, lobær pneumoni

eller bronkitis) i forbindelse med kighoste er anført i et studie.

Der fandtes ikke signifikant forskel i de to grupper, der blev

behandlet med hhv. aureomycin (chlortetracyclin) syv ud af

96 (7%) og chloramphenicol fem ud af 98 (5%).

Otitis media blev rapporteret hos ingen ud af 76 (0%), der

blev behandlet med clarithromycin (syv dage) og hos seks ud

af 77 (8%) behandlet med erythromycinestolat (14 dage).

Der var ikke nogen signifikant forskel på forekomsten af

luftvejskomplikationer, når man sammenlignede resultaterne

af clarithromycin- og erythromycinbehandling.

Bivirkninger

Bivirkninger er rapporteret i seks undersøgelser med i alt 975

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deltagere. Der kunne ikke foretages en metaanalyse, da der

blev anvendt forskellige antibiotika.

En undersøgelse viste, at tre dages azithromycinbehand-

ling sammenlignet med 14 dages erythromycinbehandling

medførte færre bivirkninger (relativ risiko (RR) 0,38; 95%

konfidensinterval (KI) 0,19-0,75).

Tilsvarende har man i en anden undersøgelse fundet, at

clarithromycinbehandling i syv dage havde færre bivirknin-

ger end erythromycinbehandling i 14 dage (RR 0,72; 95%

KI 0,53-0,97).

Komplians

I et studie fandt man, at kompliansen var bedre hos pa-

tienter, der fik erythromycinethylsuccinat, end hos pa-

tienter, der fik erythromycinestolat (RR 0,80; 95% KI 0,69-

0,94).

I et andet studie fandt man, at der var bedre komplians

med clarithromycin end med erythromycinestolat (vægtet

middeldifference 9,90; 95% KI 5,34-14,46).

I Danmark er erythromycin-ethylsuccinat, men ikke ery-

thromycinestolat et indregistreret lægemiddel.

Antibiotics for whooping cough (pertussis)

Altunaiji S, Kukuruzovic R, Curtis N, Massie J

This review should be cited as: Altunaiji S, Kukuruzovic R,

Curtis N, Massie J. Antibiotics for whooping cough

(pertussis). The Cochrane Database of Systematic Reviews

2005, Issue 1. Art. No.: CD004404.pub2.

DOI: 10.1002/14651858.CD004404.pub2.

A substantive amendment to this systematic review was last

made on 17 November 2004. Reviews are regularly checked

and updated if necessary.

Background

Whooping cough is a highly contagious disease. Infants are

the population at highest risk of severe disease and death.

Erythromycin for 14 days is recommended for treatment

and contact prophylaxis but this regime is considered incon-

venient and prolonged. The value of contact prophylaxis is

uncertain.

Objectives

To study the benefits and risks of antibiotic treatment of and

contact prophylaxis against whooping cough.

Search strategy

The Cochrane Central Register of Controlled Trials (CENTRAL)

(The Cochrane Library Issue 1, 2004); MEDLINE (January

1966 to February 2004); EMBASE (January 1974 to August

2003); conference abstracts and reference lists of articles

were searched. Study investigators and pharmaceutical

companies were appro ached for additional information

(published or unpublished studies). There were no constraints

based on lan guage or publication status.

Selection criteria

All randomised and quasi-randomised controlled trials of

antibiotics for treatment of and contact prophylaxis against

whooping cough were included in the systematic review.

Data collection and analysis

At least three reviewers independently extracted data and

assessed the quality of each trial.

Main results

Twelve trials with 1720 participants met the inclusion cri-

teria. Ten trials investigated treatment regimens and two

investigated prophylaxis re gimens. The quality of the trials

was variable. Results showed that short-term antibiotics

(azithromycin for three days, clarithromycin for seven days, or

erythromycin estolate for seven days) were equally effective

with long-term antibiotic treatment (erythromycin estolate or

erythromycin for 14 days) in the microbiological eradication

of Bordetella pertussis (B. pertussis) from the naso-pharynx.

The relative risk (RR) was 1.02, 95% confidence interval (CI)

0.98 to 1.05. Side effects were fewer with short-term treat-

ment (RR 0.66; 95% CI 0.52 to 0.83). There were no dif-

ferences in clinical improvement or micro-biological relapse

between short- and long-term treatment regimens. Contact

prophylaxis (of contacts older than six months of age) with

antibiotics did not significantly improve clinical symptoms

or the number of cases that developed culture positive

B. pertussis.

Authors' conclusions

Antibiotics are effective in eliminating B. pertussis from

patients with the disease, render ing them non-infectious,

but do not alter the subsequent clinical course of the illness.

Effective regimens include: three days of azithromycin, seven

days of clarithromycin, seven or 14 days of erythromycin

estolate, and 14 days of erythromycin ethylsuccinate. Consi-

dering microbiological clearance and side effects, three days

of azithro mycin or seven days of clarithromycin are the best

regimens. Seven days of trimethoprim/sulfamethoxazole also

appeared to be effective for the eradication of B. pertussis

from the nasopharynx and may serve as an alternative anti-

biotic treatment for patients who cannot tolerate a macrolide.

There is insufficient evidence to determine the benefit of

prophylactic treatment of pertussis contacts.

Abstract

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Subgruppeanalyse af tre studier over langtidsbehandling

(14 dage) versus korttidsbehandling (3-7 dage)

Mikrobiologisk eradikation

Subgruppeanalysen af 252 patienter viste, at 14 dages behand-

ling med erythromycin (uspecifikt salt) ikke var bedre end

korttidsbehandling med azithromycin i tre dage, erythromy-

cinestolat i syv dage eller clarithromycin i syv dage til at opnå

mikrobiologisk eradikation af bakterien B. pertussis (RR 1,02;

95% KI 0,98-1,05).

Mikrobiologisk tilbagefald

Mikrobiologisk tilbagefald er opgjort i en undersøgelse,

hvor en gruppe på 72 patienter blev behandlet med erythro-

mycinestolat i syv dage, og en anden gruppe blev behandlet i

14 dage. Undersøgelsens resultater viste, at syv dages behand-

ling ikke var forbundet med flere tilbagefald (RR 3,45; 95% KI

0,14-83,44).

Bivirkninger

I tre undersøgelser med i alt 443 deltagere blev der rapporteret

om bivirkninger. Metaanalysen viste færre bivirkninger ved

syv dages behandling end ved 14 dages behandling med ery-

thromycin (RR 0,66; 95% KI 0,52-0,83).

Antibiotika som profylakse mod kighoste

I profylaksestudierne var der lidt færre kighosteanfald hos

husstandskontakterne i behandlingsgruppen end i placebo-

gruppen, men forskellen var ikke statistisk signifikant. Blandt

vaccinerede og ikkevaccinerede kontakter fandt man, at in-

gen af de vaccinerede kontakter fik kighoste. Af de ikkevacci-

nerede kontakter, fik fire ud af 20 (20%) kighoste i behand-

lingsgruppen og to ud af 11 (18%) i placebogruppen (RR 1,10;

95% KI, 0,24-5,08).

Bivirkninger

Studierne viste flere bivirkninger (kvalme, opkast, diare og

mavesmerter) i gruppen, der fik erythromycinestolat, 49 ud af

144 (34%), end i placebogruppen, 26 ud af 166 (16%) (RR 2,17;

95% KI 1,43-3,31).

Komplians

Kompliansen var bedre i placebogruppen, 78 ud af 144

(54,2%), end i erythromycinestolat-gruppen, 108 ud af 166

(65,1%), hvilket var på grænsen til at være signifikant (RR 0,83;

95% KI 0,69-1,00).

Cochrane-analysens styrke og svagheder

På trods af at der i perioden 1953-2002 blev publiceret flere hun-

drede artikler, der omhandlede antibiotikaanvendelse i forbin-

delse med kighoste, var der kun 12 studier, der opfyldte kriteri-

erne for randomiserede eller kvasirandomiserede, kontrollerede,

kliniske undersøgelser. Det er slående, at det totale antal rando-

miserede, kontrollerede undersøgelser er så få. Mange af studi-

erne er små og inkluderer i gennemsnit 143 deltagere med en

spændvidde på 22-317. Dette er et problem, da studierne er for-

skellige med hensyn til antibiotika, definition af kighoste, inklu-

sionskriterier, intervention og endeligt resultat. Konsekvensen

er, at en metaanalyse kun var mulig at udføre på tre af studierne,

hvori man sammenlignede korttidsbehandling med langtidsbe-

handling. I flere af studierne var der initialt inkluderet flere indi-

vider, men i studiernes forløb viste kun 30-40 % sig at være B.

pertussis-positive ved dyrkning. Dette kan skyldes forskellige

faktorer, blandt andet at B. pertussis kun kan påvises i det kata-

ralske stadie og i de første to uger efter, at hosten er begyndt. Iso-

lation af B. pertussis kan være vanskelig, og andre mikroorganis-

mer som B. parapertussis kan give lignende kliniske billeder.

Kliniske perspektiver

Kighoste er anmeldelsespligtig for børn under to år, og disse

bør indlægges med overvågning, så længe de kræver assi-

stance ved anfald (optagning, ilt og sugning). Antibiotisk

behandling er indiceret til børn under et år, og forebyggelse af

smittespredning anbefales til ældre børn og voksne, hvis der i

hjemmet er børn under fem måneder.

Den hidtil anbefalede behandling med 14 dages erythro-

mycin kan eventuelt erstattes med et nyere makrolid såsom

clarithromycin eller azithromycin, men der foreligger endnu

ikke dokumentation for anvendelsen af nyere makrolider til

børn under seks måneder, hvorfor erythromycin fortsat er

førstevalgspræparat til forebyggelse og behandling i denne

aldersgruppe [8]. Forfatterne af Cochrane-review’et berører

ikke problematikken om, hvorvidt man bør anvende azithro-

mycin til børn under to år. Erythromycinethylsuccinat og

clarithromycin er indregistrerede lægemidler, og der er

ikke anført nogen nedre aldersgrænse for deres anvendelse,

hvorimod azithromycin kun er indregistreret lægemiddel i

Danmark til børn fra toårsalderen [9].

I et senere studie, der ikke indgår i Cochrane-analysen, af

417 børn i alderen fra et halvt år til 16 år har resultaterne

bekræftet, at azithromycinbehandling er ligeværdig med

erythromycinbehandling, men giver færre gastrointestinale

bivirkninger [10].

Følgende antibiotikaregimener kan anvendes til behand-

ling af kighoste:

– Erythromycinethylsuccinat (40-50 mg/kg/døgn fordelt på

3-4 doser i 14 dage).

– Azithromycin (10 mg/kg en gang dagligt i tre dage).

– Clarithromycin (15 mg/kg/døgn fordelt på to doser i syv

dage).

Konklusion

Kighoste skal primært forebygges med vaccination. Antibio-

tisk behandling har kun ringe effekt på det enkelte sygdoms-

forløb, men kan være med til at nedsætte smittespredningen.

Erythromycin har hidtil været anset for at være standard-

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behandling af kighoste, men clarithromycin og azithromycin

har vist samme effektivitet og færre bivirkninger og er derfor

at foretrække, men de er kun afprøvet i behandling af kigho-

ste for aldersgruppen over seks måneder. Azithromycin er

dog ikke indregistreret til børn under to år i Danmark, hvor-

for clarithromycin bør foretrækkes til denne aldersgruppe.

Korrespondance: Birthe Høgh, Børneafdelingen 531, H:S Hvidovre Hospital,

DK-2650 Hvidovre. E-mail: Birthe.Hoegh@hh.hosp.dk

Antaget: 29. november 2005

Interessekonflikter: Ingen angivet

Litteratur

1. Pedersen T, Fisker N, Andersen PH. Spædbarn død af kighoste. EPI-NYT

2005, uge 33.

2. Christiansen AH, Andersen PH. Kighoste 2004. EPI-NYT 2005, uge 22.

3. Christiansen AH, Andersen P, Dragsted D. Kighoste 2001 og kighosteprofy-

lakse. EPI-NYT 2002, uge 45.

4. Lebel MH, Mehra S. Efficacy and safety of clarithromycin versus erythromy-

cin for the treatment of pertussis. Pediatr Infect Dis J 2001;20:1149-54.

5. Aoyama T, Sunakawa K, Iwata S et al. Efficacy of short-term treatment of

pertussis with clarithromycin and azithromycin. J Pediatr 1996;129:761-4.

6. Pillay V, Swingler G. Symptomatic treatment of the cough in whooping cough.

The Cochrane Database of Systematic Reviews 2003, Issue 4. Art.

No. CD003257. DOI: 10.1002/14651858.CD003257.

7. Altunaiji S, Kukuruzovic R, Curtis N et al. Antibiotics for whooping cough

(pertussis). The Cochrane Database of Systematic Reviews 2005, Issue 1.

Art No. CD004404.pub2. DOI: 10.1002/14651858.CD004404.pub2.

8. www.aapredbook.aappublications.org. Section 3. Pertussis. okt. 2005.

9. www.lmk.dk. Makrolider. okt. 2005.

10. Langley JM, Halperin SA, Boucher FD et al. Azithromycin is as effective as

and better tolerated than erythromycin estolate for the treatment of pertussis.

Pediatrics 2004;114:96-101.

Laboratoriediagnostik af infektion

forårsaget af Borrelia burgdorferi

STATUSARTIKEL

Overlæge Ram B. Dessau, overlæge Jette M. Bangsborg,

overlæge Tove P. Ejlertsen Jensen, overlæge Klaus Hansen,

afdelingslæge Anne-Mette K. Lebech &

afdelingslæge Christian Østergaard Andersen

Dansk Selskab for Klinisk Mikrobiologi,

Dansk Selskab for Infektionsmedicin og

Dansk Selskab for Neurologi

Specifik paraklinisk diagnostik for infektioner med Borrelia

burgdorferi (Lyme-borreliose) blev mulig ved opdagelsen af

bakterien i 1982. Siden er diagnostikken blevet forbedret,

men den har stadig begrænsninger, og det er vigtigt at tolke et

laboratorieresultat i den kliniske sammenhæng (

Tabel 1).

Direkte metoder

B. burgdorferi (Bb) kan dyrkes fra klinisk prøvemateriale i spe-

cialmedium (Barbour-Stoenner-Kelly), hvilket giver mulighed

for en definitiv diagnose. På grund af spirokætens lange gene-

rationstid tager det imidlertid 2-6 uger, før en kultur er posi-

tiv. Metoden er vanskelig og arbejdskrævende, idet påvisning

af spirokæter foretages ved mørkefeltmikroskopi. Polymera-

sekæde (PCR)-assays til påvisning af Bb-DNA er blevet udvik-

let baseret på såvel kromosomale (f.eks. flagellin, 16S rRNA)

som plasmidbårne gener (f.eks. OspA). Generelt har sensitivi-

teten været varierende og et negativt PCR-resultat udelukker

ikke Lyme-borreliose. Ingen af de direkte metoder kan bruges

i rutinediagnostikken.

Indirekte metoder

Bb har talrige immunologisk relevante antigener. Generelt er-

kender immunsystemet et stigende antal Bb-antigener i løbet

af infektionen. Det tidlige immunrespons (fra tredje uge), der

primært er af immunglobulin (Ig)M-subklassen, er typisk ret-

tet mod flagelproteinet og det ydre membranassocierede

OspC eller mod VlsE. Fra seks uger efter infektionen ses anti-

stofdannelse (IgG) mod en række andre overfladeantigener.

Anvendelse af forskellige Borrelia-genospecies

i serodiagnostik

Der er konstatereret geografisk variation i forekomsten af de

tre humanpatogene genospecies af Bb (B. garinii, B. burgdorferi

sensu stricto og B. afzelii). Mange af de forskellige diagnostisk

interessante Bb-proteiner har interspeciesvariabilitet, men der

er ikke fundet klinisk relevante forskelle. For øjeblikket anses

det således for at være tilstrækkeligt at anvende antigen fra en

enkelt genospecies i ELISA-rutinediagnostik til antistofbe-

stemmelse.

ELISA

Den hidtidig største forbedring i de serologiske test er opnået

med udviklingen af andengenerations-assays baseret på op-

rensning af enkelte særligt immunodominante og mere speci-

fikke testantigener. Specielt assays baseret på oprenset flagel

og til dels OspC har vist en signifikant øget specificitet sam-

menlignet med assays baseret på sonikeret Bb. Den diagnosti-

ske sensitivitet af specifik Bb-immunglobulin (Ig)M-detektion

kan forbedres ved anvendelse af capture-ELISA-princippet.

Novel Strategies to Inhibit Pertussis Toxin

Article

Full-text available

Mar 2022

Katharina Ernst

Pertussis, also known as whooping cough, is a respiratory disease caused by infection with Bordetella pertussis, which releases several virulence factors, including the AB-type pertussis toxin (PT). The characteristic symptom is severe, long-lasting paroxysmal coughing. Especially in newborns and infants, pertussis symptoms, such as leukocytosis, can become life-threatening. Despite an available vaccination, increasing case numbers have been reported worldwide, including Western countries such as Germany and the USA. Antibiotic treatment is available and important to prevent further transmission. However, antibiotics only reduce symptoms if administered in early stages, which rarely occurs due to a late diagnosis. Thus, no causative treatments against symptoms of whooping cough are currently available. The AB-type protein toxin PT is a main virulence factor and consists of a binding subunit that facilitates transport of an enzyme subunit into the cytosol of target cells. There, the enzyme subunit ADP-ribosylates inhibitory α-subunits of G-protein coupled receptors resulting in disturbed cAMP signaling. As an important virulence factor associated with severe symptoms, such as leukocytosis, and poor outcomes, PT represents an attractive drug target to develop novel therapeutic strategies. In this review, chaperone inhibitors, human peptides, small molecule inhibitors, and humanized antibodies are discussed as novel strategies to inhibit PT.

Inhibition of Pertussis Toxin by Human α-Defensins-1 and -5: Differential Mechanisms of Action

Article

Full-text available

Jun 2023
INT J MOL SCI

Whooping cough is a severe childhood disease, caused by the bacterium Bordetella pertussis, which releases pertussis toxin (PT) as a major virulence factor. Previously, we identified the human antimicrobial peptides α-defensin-1 and -5 as inhibitors of PT and demonstrated their capacity to inhibit the activity of the PT enzyme subunit PTS1. Here, the underlying mechanism of toxin inhibition was investigated in more detail, which is essential for developing the therapeutic potential of these peptides. Flow cytometry and immunocytochemistry revealed that α-defensin-5 strongly reduced PT binding to, and uptake into cells, whereas α-defensin-1 caused only a mild reduction. Conversely, α-defensin-1, but not α-defensin-5 was taken up into different cell lines and interacted with PTS1 inside cells, based on proximity ligation assay. In-silico modeling revealed specific interaction interfaces for α-defensin-1 with PTS1 and vice versa, unlike α-defensin-5. Dot blot experiments showed that α-defensin-1 binds to PTS1 and even stronger to its substrate protein Gαi in vitro. NADase activity of PTS1 in vitro was not inhibited by α-defensin-1 in the absence of Gαi. Taken together, these results suggest that α-defensin-1 inhibits PT mainly by inhibiting enzyme activity of PTS1, whereas α-defensin-5 mainly inhibits cellular uptake of PT. These findings will pave the way for optimization of α-defensins as novel therapeutics against whooping cough.

The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin

Article

Full-text available

Jan 2024

Pertussis toxin (PT) is a bacterial AB5-toxin produced by Bordetella pertussis and a major molecular determinant of pertussis, also known as whooping cough, a highly contagious respiratory disease. In this study, we investigate the protective effects of the chaperonin TRiC/CCT inhibitor, HSF1A, against PT-induced cell intoxication. TRiC/CCT is a chaperonin complex that facilitates the correct folding of proteins, preventing misfolding and aggregation, and maintaining cellular protein homeostasis. Previous research has demonstrated the significance of TRiC/CCT in the functionality of the Clostridioides difficile TcdB AB-toxin. Our findings reveal that HSF1A effectively reduces the levels of ADP-ribosylated Gαi, the specific substrate of PT, in PT-treated cells, without interfering with enzyme activity in vitro or the cellular binding of PT. Additionally, our study uncovers a novel interaction between PTS1 and the chaperonin complex subunit CCT5, which correlates with reduced PTS1 signaling in cells upon HSF1A treatment. Importantly, HSF1A mitigates the adverse effects of PT on cAMP signaling in cellular systems. These results provide valuable insights into the mechanisms of PT uptake and suggest a promising starting point for the development of innovative therapeutic strategies to counteract pertussis toxin-mediated pathogenicity.

Bordetella Pertussis Infection and Hearing Loss

Chapter

Nov 2023

Pertussis, also known as whooping cough, is an acute respiratory disease. The most common causative agent is Bordetella pertussis, and less frequently, other types of Bordetella may cause similar clinical manifestations and course. The first pertussis epidemic was reported in France by Guillaume de Baillou, and the illness was popularly called “Quinta” or “Quintana.” Baillou provided the first detailed clinical description of a whooping cough epidemic that occurred in 1578 [1]. Although pertussis affects all age groups, it has a more severe course in children, especially in unvaccinated individuals and infants. Vaccination is the most effective way to prevent pertussis. After whole-cell vaccines were introduced in 1940, the number of pertussis cases decreased. The acellular pertussis vaccine is more commonly used today. Bordetella pertussis infection in infants should initially be prevented by vaccination during pregnancy and cocoon strategy. The data on hearing loss (HL) associated with B. pertussis are limited.

Vaccines for Healthcare Personnel

Chapter

Jan 2023

Chapter Controlled Human Infection with Bordetella pertussis

Chapter

Mar 2023
CURR TOP MICROBIOL

Bordetella pertussis, a slow-growing Gram-negative coccobacillus and the causative agent of whooping cough, is one of the leading causes of vaccine-preventable death and morbidity globally. A state of asymptomatic human carriage has not yet been demonstrated by population studies but is likely to be an important reservoir for community transmission of infection. Such a carriage state may be a target for future vaccine strategies. This chapter presents a short summary of the characteristics of B. pertussis, which should be taken into account when developing a human challenge model and any future experimental medicine interventions. Three studies involving deliberate infection with B. pertussis have been described to date. The first of these was a scientifically and ethically unacceptable paediatric challenge study involving four children in 1930. The second was an investigation of a putative live vaccine using a genetically modified and attenuated strain of B. pertussis. Finally, a systematically constructed human challenge model using a wild-type, potentially pathogenic strain has been established. The latter study has demonstrated that deliberate induction of asymptomatic colonisation in humans is safe and immunogenic, with colonised participants exhibiting seroconversion to pertussis antigens. It has also shown nasal wash to be a more sensitive method of detecting the presence of B. pertussis than either pernasal swab or throat swab, and that B. pertussis carriage can be cleared effectively with Azithromycin. The development of this wild-type B. pertussis human challenge model will allow the investigation of host–pathogen and facilitate future vaccine development.Keywords Bordetella pertussis Human challengeCarriageImmune response

Yardstick for Managing Cough. Part 1: in Adults and Adolescent Patients >14 years of age

Article

Dec 2022

Nationwide statistics in the United States and Australia reveal that cough of undifferentiated duration is the most common complaint for which patients of all ages seek medical care in the ambulatory setting. Management of chronic cough is one of the most common reasons for new patient visits to pulmonologists. Because symptomatic cough is such a common problem and so much has been learned about how to diagnose and treat cough of all durations but especially chronic cough, this 2-part yardstick has been written to review in a practical way the latest evidence-based guidelines most of which have been developed from recent high quality systematic reviews on how best to manage cough of all durations in adults, adolescents, and children. In this manuscript, part 1 of the 2-part series, we provide evidence-based, and expert opinion recommendations on the management of chronic cough in adult and adolescent patients (>14 years of age).

Bordetella pertussis

Chapter

Jan 2010

JMM Profile: Bordetella pertussis and whooping cough (pertussis): still a significant cause of infant morbidity and mortality, but vaccine-preventable

Article

Full-text available

Oct 2021
J MED MICROBIOL

Whooping cough (pertussis) is a highly contagious respiratory bacterial infection caused by Bordetella pertussis and is an important cause of morbidity and mortality worldwide, particularly in infants. Bordetella parapertussis can cause a similar, but usually less severe pertussis-like disease. Bordetella pertussis has a number of virulence factors including adhesins and toxins which allow the organism to bind to ciliated epithelial cells in the upper respiratory tract and interfere with host clearance mechanisms. Typical symptoms of pertussis include paroxysmal cough with characteristic whoop and vomiting. Severe complications and deaths occur mostly in infants. Laboratory confirmation can be performed by isolation, detection of genomic DNA or specific antibodies. Childhood vaccination is safe, effective and remains the best control method available. Many countries have replaced whole-cell pertussis vaccines (wP) with acellular pertussis vaccines (aP). Waning protection following immunisation with aP is considered to be more rapid than that from wP. Deployed by resource-rich countries to date, maternal immunisation programmes have also demonstrated high efficacy in preventing hospitalisation and death in infants by passive immunisation through transplacental transfer of maternal antibodies.

Effects of Early Administration of Macrolides on Whooping Cough in Adolescents and Adults: A Single-center Retrospective Cohort Study

Article

Full-text available

Oct 2021

Objective This study aimed to elucidate the effects of early macrolide administration on genetically confirmed pertussis-induced cough in adolescents and adults. Methods This single-center, retrospective cohort study examined the effects of the early administration of macrolides and antitussive agents on cough secondary to pertussis. We divided the patients into two groups based on the median duration from the beginning of the cough to the initiation of macrolide administration: early macrolide administration group (EMAG) and non-early macrolide administration group (NEMAG). The clinical improvement of cough was defined as maintaining a cough awareness score of ≤3 points for 3 consecutive days. Patients The medical records of 40 patients diagnosed with pertussis (≥12 years old) who were able to maintain a cough diary and received no other antibiotics aside from macrolides were included in the study. A diagnosis of pertussis was made using the loop-mediated isothermal amplification (LAMP) test. Results The EMAG (24 patients) showed a significantly shorter total cough period than the NEMAG [16 patients; 20.0 (95% confidence interval (CI), 16-28) vs. 30.5 (95% CI, 27-40) days; log-rank test, p=0.002]. There was no significant difference in the post-administration cough periods between the EMAG and NEMAG [11.0 (95% CI, 7-19) vs. 13.0 (95% CI, 5-23) days; log-rank test, p=0.232]. Antitussive agents did not affect the cough. Conclusion The early administration of macrolides, but not antitussive agents, is effective for treating pertussis. Therefore, macrolides should be administered as soon as possible for this disease.

Azithromycin Is as Effective as and Better Tolerated Than Erythromycin Estolate for the Treatment of Pertussis

Article

Full-text available

Jul 2004
Pediatrics

Although universal immunization against Bordetella pertussis (whooping cough) infection has resulted in dramatic reductions in the incidence of pertussis, outbreaks continue to occur in countries with excellent vaccine coverage. Treatment of infection may ameliorate symptom severity during the catarrhal phase of pertussis but has no effect on established paroxysms, emesis, or apnea if given during the paroxysmal or convalescent phases. Erythromycin, recommended for treatment of pertussis to prevent transmission of infection, is poorly tolerated because of gastrointestinal side effects. We compared the safety and efficacy of erythromycin with azithromycin for treatment of pertussis in a large, randomized, controlled trial that enrolled children from primary care practices in 1 American and 11 Canadian urban centers. Children who were 6 months to 16 years of age and had cough illness that was suspected to be or was culture confirmed as pertussis were randomized to azithromycin (10 mg/kg on day 1 and 5 mg/kg on days 2-5 as a single dose) or erythromycin estolate (40 mg/kg/day in 3 divided doses for 10 days) with stratification by center. The primary outcome measure was bacteriologic cure of infection as determined by cultures of nasopharyngeal aspirates. Culture-positive participants had a second aspirate collected at the end of therapy (days 5-7 for azithromycin, days 10-12 for erythromycin) and 1 week after therapy. Bacteriologic cure was defined as negative cultures at the end of therapy. Bacteriologic relapse was defined as a positive culture 1 week after completion of therapy and after a negative end-of-therapy culture. Secondary outcomes were pertussis diagnosed by serology and polymerase chain reaction (PCR), treatment-associated adverse events, compliance, and presence of clinical symptoms at the end of the treatment course. Serology was performed using standard enzyme-linked immunosorbent assay methods. A participant was considered to have pertussis when the PCR was positive or a 4-fold increase in pertussis toxin antibody between baseline and follow-up visits was observed. PCR was performed using a 1046-bp ClaI DNA fragment from B pertussis. Adverse events (nausea, vomiting, diarrhea, any gastrointestinal complaint, or other) were determined by a parent-completed diary that was reviewed with study personnel during study visits. Compliance was measured by review of the parent medication diary during study visits and observation of medication containers by the pharmacist at study completion. Symptoms were determined by history collected by study personnel at enrollment and subsequently from the diary. The design of the study was an equivalence trial, aimed at demonstrating that the bacteriologic failure rates with the 2 therapies did not differ by >8%. For the safety analysis, all participants who received at least 1 dose of study drug were included. In the per-protocol efficacy analysis, all culture-positive participants with end-of-treatment cultures were considered. A total of 477 children were enrolled and randomly assigned to either azithromycin (n = 239) or erythromycin (n = 238). Of these children, 114 (24%) grew B pertussis from nasopharyngeal specimens (azithromycin group: 58 of 239 [24%]; erythromycin group: 56 of 238 [23%]); these children composed the efficacy cohort for the per-protocol and intention-to-treat analyses. Serology and PCR added 52 children to the number considered to have pertussis for a total of 35% (166 of 477) of all children who presented with cough illness. In the safety analysis (antibiotic side effects, compliance) and comparison of cough symptoms after treatment, all randomized children are reported in their assigned treatment group. At end of therapy, bacterial eradication was demonstrated in all 53 patients in the azithromycin group and all 53 patients in the erythromycin group with follow-up cultures available (eradication 100%; 95% confidence interval [CI]: 93.3-100). No bacterial recurrence was demonstrated in children with 1 week posttreatment nasopharyngeal cultures available (51 and 53 participants in the azithromycin and erythromycin arms, respectively [0%, 95% CI: 0-7.0; and 0%, 95% CI: 0-6.7]). No serious adverse events attributable to study drug were observed. Gastrointestinal adverse events were reported less frequently in azithromycin (18.8%; 45 of 239) than in erythromycin estolate (41.2%; 98 of 238) recipients (90% CI on difference: -29.0% to -15.7%) as a result of less nausea (2.9% vs 8.4%; 95% CI: -8.9% to -2.0%), less vomiting (5.0% vs 13.0%; 95% CI: -4.9% to -1.4%), and less diarrhea (7.1% vs 11.8%; 95% CI: -9.0% to -0.3%). Children who were randomized to azithromycin were much more likely to have complied with antimicrobial therapy over the treatment period. In the azithromycin group, 90% of children took 100% of prescribed doses, whereas only 55% of children in the erythromycin group took 100% of prescribed doses. In this large, multicenter, randomized trial, we found that azithromycin is as effective as erythromycin estolate for the treatment of pertussis in children. Gastrointestinal adverse events were much more common with erythromycin treatment than azithromycin. Compliance with therapy was markedly better with azithromycin than with erythromycin in this study.

Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin

Article

Dec 1996
J Pediatr

The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg per day for 2 weeks. The newly developed macrolides, clarithromycin and azithromycin, have been demonstrated to be superior to erythromycin because of improved absorption and a longer half-life. As a result, we conducted two separate comparison studies to evaluate the efficacies of clarithromycin, 10 mg/kg per day, twice a day for 7 days, and azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the standard erythromycin regimen. A total of 17 patients, including 10 infants 1 year of age or less, for whom pertussis had been confirmed by culture, were allocated to receive either clarithromycin or azithromycin treatment, and each patient was matched (age, sex, and immunization status) with historical control subjects who had been treated with erythromycin. Eradication rates examined at 1 week after treatment were as follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was detected in either group. All isolated strains of Bordetella pertussis were susceptible to clarithromycin, azithromycin, and erythromycin, and no change in drug susceptibility has been confirmed for the past 20 years in Japan. Because of the very low incidence of pertussis resulting from widespread use of acellular pertussis vaccination, this study did not enroll a large number of patients; however we conclude that short-term treatment with clarithromycin or azithromycin is expected to be equal or superior to the standard long-term erythromycin regimen for pertussis.

Efficacy and safety of clarithromycin versus erythromycin for the treatment of pertussis: A prospective, randomized, single blind trial

Article

Jan 2002

Pertussis is still a prevalent public health problem, and antibiotic therapy may decrease disease severity and limit communicability. Erythromycin is the recommended antibiotic for treatment and prophylaxis of pertussis; however, side effects of erythromycin limit its usefulness in some patients. Clarithromycin, a newer macrolide, has good in vitro activity against Bordetella pertussis and a better side effect profile. To compare the microbiologic and clinical efficacy and the clinical safety of a 7-day course of clarithromycin vs. a 14-day course of erythromycin in children with pertussis. Prospective, randomized, single blind (investigator), parallel group trial. Children from 1 month to 16 years of age presenting with a clinically defined pertussis syndrome were eligible for the study. After obtaining informed written consent, we randomized patients to receive either clarithromycin (7.5 mg/kg/dose twice a day for 7 days) or erythromycin (13.3 mg/kg/dose three times a day for 14 days). Nasopharyngeal cultures for B. pertussis were performed at enrollment and after end of treatment. Clinical assessments were performed at enrollment, at end of treatment and at a 1-month follow-up visit. Adverse event data were collected throughout the study. The clarithromycin (n = 76) and erythromycin (n = 77) groups were well-matched for age and previous pertussis immunization. Microbiologic eradication and clinical cure rates were 100% (31 of 31) for clarithromycin and 96% (22 of 23) for erythromycin. The clarithromycin group had significantly fewer adverse events [45% (34 of 76) for clarithromycin vs. 62% (48 of 77) for erythromycin; P = 0.035], and compliance with the medication regimen was significantly higher in these patients. A 7-day regimen of clarithromycin and a 14-day course of erythromycin were equally effective for treatment of pertussis. Clarithromycin was better tolerated than conventional erythromycin therapy.

Symptomatic treatment of the cough in whooping cough

Article

Feb 2003

Whooping cough is an important cause of childhood morbidity and mortality. There are 20 to 40 million cases of whooping cough annually world-wide, 90% of which occur in developing countries, resulting in an estimated 200 to 300 000 fatalities each year. Much of the morbidity is due to the effects of the paroxysmal cough. Corticosteroids, salbutamol (beta 2 - adrenergic stimulant), and pertussis-specific immunoglobulin have been proposed as standard treatment for the cough. Antihistamines have also been administered. No systematic review of the effectiveness of any of these interventions or others has been performed. To assess the effectiveness and safety of interventions used to reduce the severity of the coughing paroxysms in whooping cough in children and adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 2, 2003); MEDLINE (January 1966 to June 2003); EMBASE (1990 to June 2003) and LILACS (1982 to November 2001). We also scanned reference lists of identified trials and contacted authors of identified trials and relevant pharmaceutical companies. Randomised and quasi-randomised controlled trials of any intervention aimed at suppressing the cough in whooping cough; excluding antibiotics and vaccines. Two reviewers independently selected studies and extracted data. Our primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis, development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. Disagreements were resolved by discussion. Nine studies satisfied the inclusion criteria but four had insufficient data for meta - analysis of pre-specified outcomes. Studies were small and poorly reported. The largest study had a sample size of 49 and the smallest study 18. All studies were performed in industrialised settings. Eligible studies assessed diphenhyramine, pertussis immunoglobulin, dexamethasone and salbutamol. No statistically significant benefit was found for any of the interventions. Diphenhydramine did not change coughing spells (mean increase of coughing spells per 24 hours 1.9 with 95%CI - 4.7 to 8.5) and pertussis immunoglobulin no change in hospital stay (0.7 days 95% CI -3.8 to 2.4), and a mean reduction of 3.1 whoops per 24 hours [95% CI -6.2; 0.02]. Dexamethasone did not show a clear decrease in hospital stay (-3.5 days 95% CI - 15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours [-0.22 95% CI - 4.13 to 3.69]. Insufficient evidence exists to draw conclusions about the effects of any intervention for the cough in whooping cough.

Børneafdelingen 531, H:S Hvidovre Hospital, DK-2650 Hvidovre. E-mail: Birthe

Jan 2005

Korrespondance

Korrespondance: Birthe Høgh, Børneafdelingen 531, H:S Hvidovre Hospital, DK-2650 Hvidovre. E-mail: Birthe.Hoegh@hh.hosp.dk Antaget: 29. november 2005

Ingen angivet Litteratur 1

T Interessekonflikter Pedersen
N Fisker
Ph Andersen

Interessekonflikter: Ingen angivet Litteratur 1. Pedersen T, Fisker N, Andersen PH. Spaedbarn død af kighoste. EPI-NYT 2005, uge 33.

Spaedbarn død af kighoste. EPI-NYT

Jan 2005
33

T Pedersen
N Fisker
P H Andersen

Pedersen T, Fisker N, Andersen PH. Spaedbarn død af kighoste. EPI-NYT 2005, uge 33.

The Cochrane Database of Systematic Reviews

Jan 2005

S Altunaiji
R Kukuruzovic
N Curtis

Altunaiji S, Kukuruzovic R, Curtis N et al. Antibiotics for whooping cough (pertussis). The Cochrane Database of Systematic Reviews 2005, Issue 1. Art No. CD004404.pub2. DOI: 10.1002/14651858.CD004404.pub2.

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