Household Transmission of Streptococcus pneumoniae, Alberta, Canada.

Proven or presumptive multidrug-resistant Streptococcus pneumoniae pneumonia was diagnosed simultaneously in three married couples in Alberta, Canada. The pair of isolates from each couple had identical antibiotic resistance profiles, serotypes, and pulsed-field gel electrophoresis patterns. One or more of these cases could have been prevented by S. pneumoniae vaccine.

Outbreaks of Streptococcus pneumoniae (antibiotic resistant and nonresistant) have been reported from child-care centers, nursing homes, hospitals, military camps, homeless shelters, and penal institutions (1-6). Simultaneous cases within households have rarely been reported (7-11); such cases require common exposure and transmission, as well as similar likelihood of disease in the hosts or increased virulence in the pathogen.

In December 1996 and January 1997, three married couples with multidrug-resistant S. pneumoniae (MDRSP) were admitted to Foothills Medical Centre in Calgary. The couples were not admitted on the same day. None of the couples lived with children, although couple C had daily contact with children. All patients received appropriate antibiotic therapy after their culture and antibiotic sensitivity results were known. We reviewed each patient's health record (Table) and were able to contact two of the three couples for further information.

Table. Clinical and laboratory features of three couples with Streptococcus pneumoniae pneumonia

                               Couple A

Feature               Patient 1              Patient 2

Age (yrs)           62                     61

Chronic             Hypertension           Gout 3
conditions          diabetes               previous
                                           MIs(a)

Smoker              No                     No

S.                  No                     No
pneumoniae
vaccine

Recent              None                   None
antibiotics

Others in           None                   None
home

Initial             URTI(d)                URTI(d)
complaints          symptoms,              symptom,
                    cough, fever           cough, fevers

Physical exam       Febrile,               Febrile,
                    [up arrow] HR(e),      [up arrow] HR(e),
                     [up arrow]RR(f)       [up arrow] RR(f)
                    severe [down           [down
                     arrow] breath          arrow] breath
                    distress,              sounds
                     [down arrow]
                    breath
                    sounds

Chest X-ray         Right upper lobe       Right lower
(admission or       consolidation          lobe
as noted)                                  consolidation

Admitting           Right lobe             Bilateral
diagnosis           pneumonia              pneumonia

Discharge           Right upper lobe       Right lower
diagnosis           pneumonia              lobe
                                           pneumonia

Complications       Empyema,               None
                    osteomyelitis

Source of           Day 1-blood            Day 1-blood
isolate

Gram stain          Not applicable         Not
                                           applicable

Other               None                   None
potential
pathogens
when
pneumonia
diagnosed

Antibiotic
susceptibility(1)
 Penicillin         2    R                 1.5   I
 Cefuroxime         4    R                 6     R
 Ceftriaxone        1    I                 0.5   S
 TMP[down           [is greater than       [is greater than
  arrow]SMX(m)       or equal to] 32 R      or equal to] 32 R

Erythromycin        0.25 S                 0.25  S
 Serotype           14                     14
 PFGE
pattern(n)          AA                     AA

                               Couple B

Feature             Patient 1              Patient 2

Age (yrs)           72                     71

Chronic             Hypertension           COPD(c)
conditions          CAD(b)

Smoker              Yes                    Yes

S.                  Unknown                Unknown
pneumoniae
vaccine

Recent              Unknown                Unknown
antibiotics

Others in           None                   None
home

Initial             URTI(d)                URTI(d)
complaints          symptoms,              symptoms,
                    cough, fever           cough, fever
                    chest pain             chest pain,
                                           eye
                                           discharge

Physical exam       Febrile,               Febrile,
                    [up arrow] HR(e),      [up arrow] HRe,
                    RRf [down              [up arrow] RRf
                    arrow] breath          [down arrow]
                    sounds, 3 [O.sub.2]    breath
                    saturation             sounds

Chest X-ray         Bibasilar              Extensive
(admission or       consolidation          right-sided
as noted)                                  consolidation

Admitting           Pneumonia              Lobar
diagnosis                                  pneumonia

Discharge           Pneumonia              Lobar
diagnosis                                  pneumonia

Complications       None                   None

Source of           Day 1-                 Day 1-
isolate             sputum (4+(i))         sputum (3+(i))

Gram stain          GPC                    GPC resem-
                    resembling             bling $.
                    S.                     pneu-
                    pneumoniae(j)          moniae(j),
                                           GNB(k)

Other               None                   H. influenzae
potential                                  (3 + (i))
pathogens
when
pneumonia
diagnosed

Antibiotic
susceptibility(1)
 Penicillin         1.5  I                 2    I
 Cefuroxime         3    R                 4    R
 Ceftriaxone        0.75 S                 0.38 S
 TMP[down           [is greater than       [is greater than
  arrow]SMX(m)       or equal to] 32 R      or equal to] 32 R

Erythromycin        16  R                  16   R
 Serotype           9V                     9V
 PFGE
pattern(n)          BB                     BB

                               Couple C

Feature               Patient 1              Patient

Age (yrs)           39                     37

Chronic             Recurrent              Recurrent
conditions          sinusitis              sinusitis

Smoker              Yes                    Yes

S.                  No                     No
pneumoniae
vaccine

Recent              >3 courses in          >3 courses
antibiotics         previous               in previou
                    year                   year

Others in           None                   None
home

Initial             Burn, recent           Burn, rece
complaints          URTId                  URTId,
                    symptoms,              symptoms,
                    cough fever            cough feve

Physical exam       Febrile,               Febrile,
                    [up arrow]             [up arrow]
                    dis-tress              dis-tress
                    on venti-              on venti-
                    lator,                 lator,

                    [down arrow] breath    [down arrow] breath
                    sounds,                sounds,
                    crepitations           crepitation

Chest X-ray         Day 3 -                Day 2 -
(admission or       extensive              extensive
as noted)           bilateral              bilateral
                    consolidation          consolidation

Admitting           Burn                   Burn
diagnosis

Discharge           Burn                   Burn
diagnosis           complicated            complicate
                    by                     by
                    pneumonia              pneumonia
                                           fatal sepsis

Complications       None                   Died

Source of           Day 3-ETTg             Day 2-BA
isolate             (4+(i))                ([10.sup.5]
                                           CFU[down arrow]mL(i))

Gram stain          GPC                    GPC
                    resembling             resembling
                    S.                     S.
                    pneumoniae(j)          pneumonia

Other               GNB(k)                 H. influenz
potential                                  ([10.sup.3]
pathogens                                  CFU[down arrow]mL(i))
when
pneumonia
diagnosed

Antibiotic
susceptibility(1)
 Penicillin         1.5  I                 1  I
 Cefuroxime         6    R                 4  R
 Ceftriaxone        0.75 S                 0.75 S
 TMP[down           [is greater than       [is greater than
  arrow]SMX(m)       or equal to] 32 R      or equal to] 32 R

Erythromycin        0.25  S                0.25 S
 Serotype           9V                     9V
 PFGE
pattern(n)          BC                     BC

(a) Myocardial infarction.

(b) Coronary artery disease.

(c) Chronic obstructive pulmonary disease.

(d) Upper respiratory tract infection.

(e) Heart rate.

(f) Respiratory rate.

(g) Endotracheal tube.

(h) Bronchoalveolar lavage.

(i) For sputum or ETT aspirates, 3+ & 4+ reflect growth on the third and fourth set of streaks, respectively, on the culture plan for BAL, sample fluid is an approximately 100-fold dilution of lung fluid.

(j) Gram-positive lancet-shaped cocci found singly, in pairs or in short chains.

(k) Gram-negative coccobacilli.

(l) Antibiotic susceptibilities reported as MIC (micrograms/mL) and as S (susceptible), I (intermediate) or R (resistant) (NCC criteria).

(m) TMP/SMX (trimethoprim/sulfamethoxazole).

(n) Pulsed-field gel electrophoresis.

S. pneumoniae were identified by standard methods. MICs were determined by E-Test (AB Biodisk, Solna, Sweden) and classified as susceptible (S), intermediate resistant (I), or fully resistant (R) to each antibiotic, according to National Committee for Clinical Laboratory Standards guidelines (12). Serotyping of S. pneumoniae was performed by the Quellung reaction technique at the National Centre for Streptococcus, Edmonton. Electrophoretic fingerprinting of S. pneumoniae was performed by pulsed-field gel electrophoresis (PFGE) of DNA digested with Sma 1 (BRL, Gaithersburg, MD). The PFGE patterns were classified as indistinguishable, related, or different according to criteria suggested by Tenover (13).

The diagnosis of S. pneumoniae pneumonia in couple A was confirmed by positive blood cultures, chest X-ray lobar pneumonia, and disease-compatible clinical findings. Patient 1 in couple A was a health records clerk at Foothills Medical Centre. Her illness was complicated soon after admission by empyema, which was drained; the fluid was S. pneumoniae-negative. Vertebral osteomyelitis was suspected from clinical evidence 18 days after admission and was confirmed by bone scan; no diagnostic culture was obtained. Osteomyelitis in this patient was presumably caused by S. pneumoniae. The initial 7-day course of cefuroxime (to which S. pneumoniae was resistant) may not have cleared the infection and thus allowed secondary seeding to bone.

Couple B (who could not be reached for further information) had had recent visitors from Texas (one a hospital worker) with upper respiratory tract infections. S. pneumoniae pneumonia was presumptively diagnosed in this couple on the basis of symptoms, signs, and chest X-rays compatible with the diagnosis of pneumonia, as well as sputum samples, which had gram-positive lancet-shaped cocci identified on Gram stain and grew S. pneumoniae. From the sputum of patient 2 in couple B, gram-negative bacilli were identified on Gram stain; Haemophilus influenzae was also isolated. Thus, this patient may have been coinfected, or primarily infected, with H. influenzae. The patient's blood cultures were negative; a blood culture was not performed on patient 1 in couple B.

Couple C was admitted with severe bums and inhalation injuries after the stove in their two-room trailer exploded. They had had recurrent sinusitis and other respiratory infections in the previous year since moving to their trailer, which had poor air circulation. Patient 1 of this couple was taking antibiotics at the time of admission, and patient 2 had recently completed a course of antibiotics. The diagnosis of pneumonia (patient 1 on day 3 of admission and patient 2 on day 2) was made on the basis of recent upper respiratory symptoms and fever, diminished breath sounds, crepitations, and disease-compatible chest X-ray findings (previous films had been normal), which made pneumonia more likely than noninfectious conditions such as acute lung syndrome. The presumptive diagnosis of S. pneumoniae as the etiologic agent in the case of patient 1, couple C, was made on the basis of the initial endotracheal tube aspirate, which had gram-positive lancet-shaped cocci identified on Gram stain and grew S. pneumoniae. Only gram-positive lancet-shaped cocci were identified from the initial bronchoalveolar lavage of patient 2 on Gram stain, and S. pneumoniae grew in much greater numbers than H. influenzae. Blood cultures, performed for couple C only after antibiotic therapy was started, were negative. Patient 2 died of septic shock 20 days after admission, with Candida albicans in his blood. The bronchopneumonia never resolved clinically, although S. pneumoniae was not isolated from any further cultures. Thus, S. pneumoniae may have been a contributing factor to, but not likely the direct cause, of this patient's death.

The identical susceptibility patterns, serotypes, and PFGE patterns indicate that both partners in each couple were infected with the same multidrug-resistant S. pneumoniae strain. Couples A and B apparently had community-acquired pneumonia. Although couple C contracted pneumonia 48 to 72 hours after admission, each partner entered the hospital already infected with MDRSP; the infecting organisms were identical, and no other recognized cases of nosocomial MDRSP occurred at Foothills Medical Centre at the time of their admission (they were admitted 1 month before couple B, who were also infected with serotype 9V MDRSP). Couple A may have been exposed to MDRSP as a result of one partner's work in a tertiary-care hospital; couple B as a result of one partner's exposure to a health-care worker with respiratory symptoms. At the time of these cases, the prevalence of penicillin-nonsusceptible S. pneumoniae infections in Calgary was approximately 10% (A.P. Gibb, unpub, data).

None of these patients had received S. pneumoniae vaccine, yet each had one or more risk factors for infection (advanced age, exposure to young children, smoking, and chronic lung or heart disease). Couple C had a history of recent antibiotic use, the predominant risk factor for antibiotic-resistant infections.

In Canada, the S. pneumoniae vaccine is recommended for all persons [is greater than or equal to] 65 years old and persons [is greater than or equal to] 2 years with identified risk factors (14). Despite the vaccine's reasonable effectiveness, its use has been very low in Canada until recently (fewer than 12 doses per 10,000 population distributed annually [15,16]). The vaccine has been provided free of charge to persons with medical indications, but not to healthy persons 65 years of age and older and not as part of a routine vaccination schedule (17). Some provinces (including Alberta, beginning in 1998) have begun to routinely provide the vaccine to all persons at risk. The current incidence of invasive S. pneumoniae infections in Calgary is 20 per 100,000 per year overall and 87 per 100,000 per year in those older than 64 years of age (J.D. Klein, unpub, data).

Outbreaks of S. pneumoniae disease occur in institutions with crowding, poor air quality, or increased host susceptibility (2,4,6). These factors may also exist within households (9,11). Couple C, for example, lived in a very crowded space with poor air circulation.

The rate at which secondary S. pneumoniae infections occur in household contacts of index patients with invasive disease is not known, but rare cases have been reported (7-11). Factors contributing to secondary infections include the likelihood of nasopharyngeal infection due to exposure to the index patient or a common source, susceptibility to the strain of the index infection, and likelihood that colonization will lead to disease rather than to development of asymptomatic immunity. Data on contemporaneous nasopharyngeal carriage of the outbreak strain by household contacts are limited. A recent study from Gambia found carriage in 8.5% of household contacts, compared with 21% in an older U.S. study (18,19). In healthy adults, the prevalence of circulating S. pneumoniae antibodies is low (4% to 34%, depending on the serotype); however, two thirds of adults have protective antibody within 1 month of colonization (20). Approximately 15% of children who acquire a new S. pneumoniae strain nasopharyngeally in a nonoutbreak setting acquire clinical disease (usually otitis media); this rate is unknown for adults (21). In contrast, during a recent nursing-home pneumonia outbreak, 23% of residents were infected with the S. pneumoniae outbreak strain, and 4% became ill (22). The median age of residents was 85 years; only 4% had received S. pneumoniae vaccine.

Increased use of S. pneumoniae vaccine may prevent MDRSP pneumonia within households and among persons living in crowded conditions.

Acknowledgments

We thank Sheila Robertson for performing the chart reviews, James Talbot and Marguerite Lovgren for serotyping, and Kevin Fonseca for directing the pulsed-field gel electrophoresis.

References

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(14.) National Advisory Committee on Immunization. Canadian Immunization Guide. 4th ed. Ottawa: Health and Welfare Canada, 1993.

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(17.) Epidemiology CDCA. Alberta immunization manual. Edmonton: Alberta Health; 1996.

(18.) Lloyd-Evans N, O'Dempsey T J, Baldeth I, Secka O, Demba E, Todd JE, et al. Nasopharyngeal carriage of pneumococci in Gambian children and their families. Pediatr Infect Dis J 1996;15:866-71.

(19.) Smillie WG, Jewett OF. The relationship of immediate family contact to the transmission of type-specific pneumococci. American Journal of Hygiene 1940;32:79-88.

(20.) Musher DM, Groover JE, Rowland JM, Watson DA, Struewing JB, Baughn RE, et al. Antibody to polysaccharides of Streptococcus pneumoniae: prevalence, persistence and response to revaccination. Clin Infect Dis 1993; 17:66-73.

(21.) Gray BM, Converse III GM, Dillon HC. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 1980;142:923-33.

(22.) Nuorti JP, Butler JC, Crutcher JM, Guevera R, Welch D, Holder P, et al. An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among unvaccinated nursing home residents. N Engl J Med 1998;338:1861-8.

James D. Kellner,(*)([dagger]) A. Patrick Gibb,([dagger])([double dagger]) Jenny Zhang,([sections]) and Harvey R. Rabin(*)([dagger]) (*) Foothills Medical Centre and Alberta Children's Hospital, Calgary, Alberta, Canada; ([dagger]) University of Calgary, Alberta, Canada; ([double dagger]) Calgary Laboratory Services, Alberta, Canada; and ([sections]) Provincial Laboratory of Public Health, Calgary, Alberta, Canada

Dr. Kellner is an assistant professor of Pediatrics and Microbiology and Infectious Diseases at the University of Calgary, Canada. His research interests include S. pneumoniae infections and antimicrobial resistance.

Address for correspondence: James D. Kellner, Division of Infectious Diseases, Alberta Children's Hospital, 1820 Richmond Road, SW, Calgary, Alberta T2T 5C7, Canada; fax: [phone]; e-mail: [e-mail].