Non-classical pneumococcal infections

(endocarditis, peritonitis, conjunctivitis,

sinusitis, neonatal sepsis)

Zsofia Meszner MD PhD

‘Heim Pál’ National Institute of Child Health

‘Szent László’ Hospital for Infectious

Diseases

Budapest, Hungary

2

Pneumococcal disease: it all starts with

nasopharyngeal carriage (NPC)

Acute Otitis

Media (AOM)

Pneumonia

Bacteraemia

Antibiotic resistance

Spread to other individuals

Meningitis

ECDC. Pneumococcal infection – Factsheet for health professionals. October 2011.

Non-classical pneumocococal infections

Common characteristics:

• Rare, difficult to find correct data as to incidence, prevalence in

childhood

• Diagnosis depends upon awareness, culturing practice, possibilities

and intention

IPD – non-IPD

• Pneumococcal endocarditis, peritonitis, neonatal sepsis are

IPD syndromes, as opposed to pneumococcal conjunctivitis and

sinusitis

Pneumococcal endocarditis*

*www.hindawi.com/journals/crim/2010/982521/fig1/

Pneumococcal endocarditis

• Incidence of infective endocarditis/IE in adults (USA) has

been reported to be 1.5-6.0 per 100,000 patient years*

• IE incidence in children in general population is

approximately three times lower2**

• Pneumococcal endocariditis is responsible for <2% of all

IE***

*Pasquali SK et al : Trends in endocarditis hospitalizations at US children’s hospitals: impact of the 2007

American Heart Association Antibiotic Prophylaxis Guidelines. Am Heart J. 2012, 163:894-899.

** Ravindranath Waikar et al. Cureus, 2019, 11(3):

*** Perier A, Int J Cardiol. 2019 Aug 1;288:102-106

Method:

• This multicentric observational retrospective study included adult patients

presenting with definite S. pneumoniae IE according to modified Dukes

criteria from four French university hospitals between 2000-2015.

• Survival rate at 90 days and 2 years after diagnosis, appropriateness of

antibiotherapy, and pneumococcal vaccination status were determined.

• Risk factors for mortality were studied by univariate analysis.

Results:

• 50/3886 (1,3% of all) IE had pneumococcal IE

• Mostly males - with a mean age of 60 ± 14 years.

• Predisposing conditions for IE or for invasive pneumococcal disease

(IPD) involved 24% and 78% of the cases, respectively.

• Only 2 patients were vaccinated against pneumococcus before IE and

13 (26%) after IE.

• Antimicrobial strategy was in accordance with the 2015 ESC Guidelines

in 28%.

• Cardiac surgery was performed in 56%, and was associated with better

survival (p = 0.012).

• In the 40/50 patients followed until 2 years, the survival rate was 67%,

deaths occurring mostly before 90 days.

• Age ≥ 65 was a risk factor for mortality (p = 0.011).

Conclusion:

• Pneumococcal IE remains rare but with a poor prognosis.

• Resort to surgery is yet to be determined, improves survival.

• Predisposing conditions for IPD are the main factors leading to

pneumococcal IE.

• They could be prevented by vaccine coverage improvement !!

• The Austrian syndrome* is a pathology caused by disseminated Streptococcus

pneumoniae infection and characterized for the triad of pneumonia,

endocarditis and meningitis.

• It has an estimated incidence of 0.9-7.8 cases per ten millions people each

year, and a mortality of 32%.

• Alcohol abuse, as the main risk factor, appears only in four out of ten patients.

• 14% of patients do not have any risk factor.

• Two out of three patients are males and it occurs in the middle aged of life.

• It is more frequently on native valve, aortic valve is injured in the half of the

cases. Severe regurgitation occurs in two per three patients.

• Appropriate antimicrobial treatment and early endocarditis surgery decrease

mortality.

• It is possible that Austrian syndrome epidemiology is changing by the

introduction of 13-valent pneumococcal conjugated vaccine in the

children´s calendar.* Described by Osler in 1881.

Anamnesis:

• a 3-week history of productive cough, rhinorrhea, non-bloody non-bilious emesis

• intermittent fevers with a maximum temperature of 102 °F

• treated for pneumonia twice in the past six months + recurrent ear infections

• was diagnosed to have moderate persistent asthma a year ago

• uncomplicated birth history

• no history of any structural heart disease or any other congenital defects

• the child was up to date with vaccines including four doses of pneumococcal

conjugate vaccine (PCV)13

• there was no family history of recurrent infections, immunodeficiency,

consanguinity, or cardiac problems

Diagnosis:

• Chest X-ray: opacification in the right lower lobe

• Cardiac echocardiography: 3-mm vegetation on the anterior mitral valve leaflet

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Primary blood culture:

• Streptococcus pneumoniae, serotype 3N sensitive to penicillin G and ceftriaxone

Outcome:

• Recovery after 4-w of AB treatment, Follow up echocardiogram one month:

resolution of vegetation

Discussion/literature:

• Mayo clinic* – between 1950-2011

– 97 IE, one case of pneumococcal endocarditis

• 5-year long study/Japan**

– 2/170 cases of pneumococcal endocarditis, both with no risk factors

• US Pediatric Multicenter Pneumococcal Surveillance Group*** prospective study,

eight major centers with invasive disease due to S.pneumoniae – between 1993-2003.

– 11 cases/3065 – only one child had no history of structural heart disease!

*Johnson JA et al: Infective endocarditis in the pediatric patient: a 60-year single-institution review. Mayo Clin Proc. 2012, 87:629-635.

**Ishiwada N et al: Pneumococcal endocarditis in children: a nationwide survey in Japan. Int J Cardiol. 2008, 123:298-301

***Givner LB et al: Pneumococcal endocarditis in children . Clin Infect Dis. 2004, 38:1273-1278

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Risk factors for Pneumococcal disease and

complications*

• Immunocompetent children– Chronic heart disease

– Chronic lung disease

– Diabetes mellitus

– CSF leaks

– Cochlear implants

• Children with functional or anatomic asplenia– Sickle cell disease and other hemoglobinopathias

– Congenital or aquired asplenia or splenic dysfunction

• Children with immunocompromised conditions– HIV infection

– Chronic renal failure and nephrotic syndrome

– Disease associated with treatment with immunosuppressive drugs or radiation therapy, or

solid organ transplantation

– Congenital immunodeficiency

*CDC MMWR Recomm Rep 2010;59(RR-11):1-18.

Summing up pneumococcal endocarditis

• rare condition, but may occur in any age

• majority of cases above 65ys

• in children extremely rare

• majority with risk factors/underlying heart conditions

• PCVs in pediatric immunization programs have an

impact on incidence

Note:

• there are occasional cases in immunocompetent,

otherwise healty children too

Pneumococcal peritonitis*

*IDCases, Volume 15, 2019, e00489

Pneumococcal peritonitis

• Tis a form of primary peritonitis(PP), what is a diffuse infective inflammation of the

peritoneal cavity in the absence of a localized source – mainly caused by Gram

negative bacteria, extremly rarely by pneumococcus

• ..is a rare occurrence and represents a clinical challenge because of its subtle and

non-specific clinical findings.

• ..in current literature generally „case reports” can be found

• ..in adults, the so called „primary peritonitis” without an identifiable intra-abdominal

source is extremely rare in healthy individuals;

• T PP is commonly seen in cases of nephrotic syndrome, cirrhosis and end-stage

liver disease, ascites, immunosuppression, and inflamed peritoneum due to pre-

existing autoimmune and oncological conditions

PP due to S. pneumoniae in children

• Pediatric cases are known for nearly a hundred years*

• PP due to pneumococcus occurs almost always in females

• S.pneumoniae may reach the peritoneal cavity by migration via the female genital

tract

• The symptoms usually mimick acute appendicitis

• PP is a rare complication of idiopathic nephrotic syndrome (INS) in children- may lead

to end-stage disease!

• Immunisation with the 13-valent pneumococcal conjugte vaccine is of great

importance!!

*Armitage TG, Williamson RCN. Primary peritonitis in children and adults. Postgrad

Med J 59: 21–4, 1983,.

Dugi DD 3rd, Musher DM, Clarridge JE 3rd, Kimbrough R. Intraabdominal infection

due to Streptococcus pneumoniae. Medicine (Baltimore). 2001;80:236–44

Neonatal sepsis due to pneumocaccal

infection:

„early onset”* vs. „late onset”

*https://parenting.firstcry.com/articles/neonatal-sepsis-causes-symptoms-treatment/

Burden of Pneumococcal Disease in Children

Adapted from CDC. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/pneumo.pdf.

Accessed September 10, 2008.

otitis media

pneumonia

Severity of

disease

No

nin

vasiv

eIn

vasiv

e

Each case of meningitis:

>x 1,000

>x 100

x 10

Incidence

Real “burden of disease” is underestimated because specific diagnosis of

pneumonia and otitis media is difficult; blood cultures, chest-x-ray, and

punctures are not routinely performed

meningitis

bacteremia/

sepsis

• Textremly rare, with high (approx. 60-70%) mortality

• Tis usually acquired intrapartum, from the colonization of the maternal

genital tract

• Tearly-onset presentation of symptoms, usually within the first 48 hours

after birth

• T the virulence seems to be higher for S.pneumoniae, which has in

addition a higher infant invasion/ maternal colonization ratio than

Streptococcus Agalactiae.

• Pneumococcal vaccination has not resulted in a significant decline of

neonatal cases.

• Strategies to prevent early- onset neonatal S.pneu sepsis (NSPS) are

evolving

• Some interventions worth considering for prevention:

– treatment for all pregnant women with a positive vaginal culture to

S.pneumoniae,

– clinicians’ increased awareness of SPNS and prompt aggressive

antibiotic treatment of affected neonates

– further surveillance studies

– assessment of risk factors for SPNS,

– as well as evaluation of other strategies such as vaccination during

pregnancy, aiming to protect these infants are needed.

Pneumococcal conjunctivitis*

* AAP Gateway

Pneumococcal conjunctivitis

• Symptoms

– redness; gray or yellow discharge; itching, burning, pain, or dryness; and crusting

in the morning.

• Diagnosis

– generally uncapsulated S.pneumoniae

• Unusal, though sometimes may cause outbreaks

– schools, college campuses

• Risk factors significantly associated with conjunctivitis*

– having close contact with someone with conjunctivitis

– attending a party

– living in a fraternity or sorority house

– wearing contact lenses, sleeping with them

– being a first-year student

*N Engl J Med 2003; 348:1112-1121

• 1,3% of all conjunctivitis cases are caused by bacteria– S.aureus > H,influensae > S.pneumoniae > M.catarrhalis

• Apart from the well-known „classical” pneumococcal syndromes,

S.pneumoniae– is also one of the top pathogens contributing to bacterial keratitis and conjunctivitis

– has several virulence factors that wreak havoc on the conjunctiva, cornea, and intraocular

system.

• Virulence factors playing a role– Pneumolysin (PLY) is a cholesterol-dependent cytolysin that acts as pore-forming toxin

– Neuraminidases assist in adherence and colonization by exposing cell surface receptors to

the pneumococcus

– Zinc metalloproteinases contribute to evasion of the immune system and disease severity.

• Outcome– Conjunctivitis – good; keratitis – possible scaring; endophtalmitis – visual loss!!

Pneumococcal sinusitis*

*www.medicinenet.com/sinusitis/article.htm

Rhinosinusitis - basic facts

• Tis not rare:

– affects many pediatric patients as well as 1 in 6 adults in any given year,

resulting in ambulatory care, pediatric, and emergency department visits.

• Tuncomplicated rhinosinusitis

– requires no imaging or testing and does not require antibiotic treatment.

• Tusing strict clinical diagnostic criteria

– may minimize unnecessary antibiotics.

• Twhen indicated

– amoxicillin with or without clavulanate for 5 to 10 days remains the first-line

antibiotic, despite increasing incidence of staphylococcal sinusitis in the post-

pneumococcal conjugate vaccine era.

• Temergency providers also need to recognize

– atypical cases in which uncommon but serious complications of sinusitis cause

both morbidity and mortality

Clinical manifestations

• acute catarrhale sinusitis – as part of any URTI

• acute purulent rhinosinusitis (ABRS)• bacterial – S.pneumoniae

• fungal

• dentogen

• chronic sinusitis• risk factors

• irritation

• alien bodies, etc.

The role of risk factors in rhinosinusitis

• Risk factors– „host” faktorok

• age

– infants – immunological/anatomical immaturity

– elderly – immunologically senile („senile” T ly)

• underlying diseases

– mucoviscidosis, diabetes mellitus, mucociliary defectT

– immunosuppressivev treatment, malignant disease

– anatomical defect – septum deviation, atresia

– polyp, tumor

– „environmental” – indirect „host” factors• environmental

– smog, smoke, swimming poolsT

• alien bodies, trauma, iatrogen (tooth extraction)

Acute bacterial rhinosinusitis - ABRS

• Antibacterial treatment is necessary only in selected

cases:

– non specific signs and symptoms of URTI (rhinorrhoea, cough,

mainly) persisting for the minimum of 10 days without

improvement

– acute sinusitis creates diagnostic difficulty due to the lack of

sensitive and specific tests to discriminate viral from bacterial

etiologies in primary care settings.

– the diagnosis of acute bacterial sinusitis is usually based on

clinical criteria, and it is uncommon in patients who have been ill

for less than 10-14 days. Sinus inflammation is common with a

viral URI, but these symptoms resolve after 7-10 days. Patients

who continue to have symptoms without improvement for 10-14

days may have a bacterial infection.

Acute bacterial rhinosinusisits - ABRS

• In rare cases, patients may present with more severe signs of acute

bacterial sinusitis. These often include fever, facial swelling, facial pain,

and maxillary tooth pain.

• Most cases of sinusitis are self-limited, but antibiotic treatment confers a

modest benefit. In uncomplicated cases, use a narrow spectrum drug such

as amoxicillin for initial treatment. Strains of pneumococci with

intermediate penicillin resistance can still be effectively treated with

amoxicillin.

• deteriorating general condition (e.g. high grade fever 39ºC, facial swelling

and pain, maxillary pain after 5-7 days)

• need to treat at once, if serious complications occur (ethmoiditis,

celullitis orbitae)

13-PCVs in NIPS have reduced the pneumococcal sinusitis burden

considerably

mészner

• Aims:

– All children 0 to <18 years old hospitalized for sinusitis, pneumonia, or

empyema in Stockholm County, Sweden, from 2003 to 2012 were

included in a population-based study of hospital registry data on

hospitalizations due to sinusitis, pneumonia, or empyema.

• Results:

– Hospitalizations for sinusitis decreased significantly in children

aged 0 to <2 years, from 70 to 24 cases per 100 000 population (RR =

0.34, P < .001)

• Conclusions:

– PCV7 and PCV13 vaccination led to a 66% lower risk of

hospitalization for sinusitis

Take home messages

• Non-classical pneumococal infection

– may generally be uncommon - though might lead to life threatening courses and

complications

• Pneumococcal endocarditis

– usually occurs with underlying conditions and risk factors

– unique cases may occur in otherwise healthy and immunocompetent children

• Pneumococcal peritonitis

– may mimick appendicitis in competent hosts

– nephrosis sy poses risk for it

– more often occurs in females

• Pneumococcal neonatal sepsis

– ‚early onset’ has an acceptable high mortality

– needs new strategies for prevention and treatment

• Pneumococcal conjunctivitis

– may have outbreaks

• Pneumococcal sinusitis– PCV childhood immunisation programs greatly reduced the burden

mészner

zsofia.meszner@heimpalkorhaz.hu