Bacteremic pneumonia caused by penicillin-resistant pneumococci : Case report and review with a Canadian perspective

A Canadian adult with bacteremic pneumonia caused by a relatively penicillin-resistant (minimal inhibitory concentration 0.25 μg/mL) Streptococcus pneumoniae is reported, and the published literature regarding penicillin-resistant pneumococci in Canada reviewed. Although penicillin resistance has been reported infrequently to date, this case emphasizes the need for routine antimicrobial sensitivity testing of all pneumococci isolated from normally sterile sites, and for ongoing systematic surveillance for penicillin and other antibiotic resistance in Canada.

P ENICILLIN G REMAINS TI-l E ANTIMI CROBIAL AGENT OF choice for the treatment of pneumococcal infections.Since 1967, however.when a pn eumococcus that was re latively resistant to penicillin was first reported from Australia (1). a n increasing prevalen ce of both rela tive ly resistant (minimal inhibitory concentration IMIC] 0.12 to 1.0 pg/mL) and resistant (MIC greater than or eq ual to 1.0 pg/mL) pne umococci has been noted in many parts of the world (2).
To date, penicillin-resistant pn eumococci h ave been infrequently reported from Canada .The authors present t11e case of an adult from Vancouver.British Columbia who developed bacteremic pneumococcal pneumonia witl1 an isolate th at was relatively resistant (MIC 0.25 pg/mL).and review the published literatu re regarding penicillin-resistant pne umococci in Canada .

CASE PRESENTATION
A 68-year-old man was admitted to hospital witll a diagnosis of right lower lobe pneumonia.Past m edical history was significant for myocardia l infarction at age 33 years and for repair of pe rforated peptic ulcer one year prior to admission.He was a heavy smoker a nd consumed six to eight ounces of alcohol daily.The patient was on no m edica tion.had no t been recently hospital ized, and h ad not received any recent antimicrobial therapy.
Physical examination revealed a blood pressure of 110/70 mmHg , a heart rate of 130 beats/min a nd a tempe rature of 38.3°C.The respiratory rate was 23/ min, and there were findings consistent wiU1 right lower lobe conso lida tion.The remainder of U1e physical examination was normal.Investigations revealed a he moglobin of 122 g/L and a white blood cell coun t of 2 1. 9xl0 9 /L.Arteria l blood gas analysis on room a ir revealed pH 7 .51. p02 51 mmHg a nd pC02 28 mmHg.Gram stain of e>..rpectorated sputum revealed more t11an 25 epithelia l cells per low power field .and t11e specimen was deem ed unacceptable for culture.Ch est x-ray s h owed an infiltrate consistent witl1 right lower lobe pneumonia.
The patient was treated with oxygen, intravenous Uliamine and in travenous cefuroxin1e 1.5 g every 8 h.Blood c ul tures taken on a dmission grew Gram-positive cocci in ch ains 24 h la ter.Cefuroxime was discontinued and intravenous penicillin G two million units every 6 h was commen ced.1\vo days after a dmission.there was sudden clinical deterioration witl1 respiratory distress.decreased level of consciousness and cyanosis.The patient was transferred to the intensive care unit and required intubation and mech anical ventilation.Electrocardiography and cardiac en zymes were consisten t with ac ute myocardial infarction .Ch est x-ray showed new bilateral basilar infiltrates.and antibiotic therapy was changed to intravenous imipen em 1 g every 8 h to treat probable hospital-acquired aspiration pneumonia superimposed on the pneumococcal pneumonia.
Two sets• of blood cultures drawn on admission to hospital grew Streptococcus pne wnoniae.The organism was reported to b e resistant to penicillin and sensitive to an1picillin , e rythromycin, clindamycin .vancomycin.c hlora mphenicol.tetracycline and imipen em .lmipenem therapy was continued and t11e patient slowly recove red.Follow-up blood cultures on imipenem ilierapy we re ste rile .Unfortunately. 20 days after admiss ion. the patient suffered acute card iopu lmonary a rrest and died , despite a ttempts at resuscitation.Autopsy revealed t11e cau se of deatl1 to be a new myocardial infarction.Histopathological examination of the lungs revealed an organizing pneumonia with diffu se a lveolar dan1age.but no acute inflammato ry infiltrate.No Gram-positive cliplococci were demonstrated on tissue Gram smears .

MICROBIOLOGICAL METHODS AND RESULTS
Blood culture isolates of Strep pneumoniae were identified according to standard me t11ods.Susceptibility testing was performed at t11e Un ive rsity Hospital (Shaughnessy site) microbiology la boratory by modified Kirby-Bauer procedure using a 1 pg oxacillin disk on Mu eller-Hinton aga r supplemented witl1 5% lysed horse blood.MIC testing to penicillin was performed by micro-brotl1 dilution technique (Sensititre: Racliometer/ Copenh agen Co. Oh io) using a supplementation of 5% s h eep blood, as described by D'Amato et al (3).Entero• coccLLsjaecalis ATCC strain 29212 was u sed as a control.Two different morphotypes were observed on subculture to sheep blood agar which gave zon e s izes of 0 a nd 11. 5 mm.respectively.to a 1 pg oxacillin disk.Both were s uscepti ble to tetracycline.a mpicillin.eryUlromycin, clindamycin , vancomycin and imipen em.The MI C of penicillin for both morphotypes was 0.25 pg/mL.The organism was serotyped as type 14 by the National Centre for Streptococci at t11e Provincial Laboratory of Public Health in Edmonton.Alberta.

DISCUSSION
The first report of a penicillin-resistant pneumococcus came from Australia in 1967 (1).Since then.resistant stra ins have been reported from m any countries.a nd in som e a reas t11e prevalence of penicillin-resistant pneumococci is now extremely high.In Sout11 Africa.for example, 8 .4 to 62.2% of pneumococcal isolates have a n MIC greater than or equal to 0 .1 ~tg/mL (2) .OU1er areas witl1 hig h rates of res istance (MIC greater than or eq u a l to 0 .1 ~tg/mL) include Spain (19 .5 to 52%) (4.5).Israel (28 .4%)(6).Poland (26.7%) (2) and New Guinea (12.5 to 33 .3%)(7).Serial surveillance reveals that rates and degree of penicillin resistance are increas ing in m a ny of these areas .For example.Klugman and Koornhof (8) surveyed blood cult ure isolates in South Africa and found t11at, in 1979, 3.8% of isolates were penicillin resistan t (MIC greater than or equal to 0 .J pg/mL).while in 1986.14.1% of isolates were resistant.
Isolates with resistance to multiple antibiotics are also being reported with increasing frequency.
In the United States, ther e is considerable vaJiabili ty in the prevalence of penicillin-resistant pneumococci from region to region.The Centers for Disease Control conducted a national s urveillance stu dy from 1979 through 1985 and found that 126 of 340 0 isolates (3.7%) from normally sterile body sites (cerebrospinal l1uid, blood) were relatively penicillin resistant (MIC 0.1 to 1.0 ~g/mL) (9).There was only one isolate that was resistant (MIC 4 ~g/mL) .However, surveys of specific populations or geographic areas have demonstrated much higher rates of resistance, including 22 of 197 (11.2%) in Alaska (10) and 17 of 139 (12.2%) in Oklahoma City (11).
The first major Canadian sunrey of Strep pneumoniae was reported by Dixon et al (12) in which 6000 clin ical isolates obtained from northern Alberta and the adjacent Northwest Territories during 1974-76 were studied.Relative resistance to penicillin (MIC greater than or equal to 0.16 pg/mL) was detected in 143 isolates (2 .4%)which came from the nasopharynx (96).ear (32).eye (eight), sputum (five) and skin (two) .None of the organisms was isolated from blood or a normally sterile site.and the majority of isolates were from children under six years of age.None of the isolates demonstrated high level resistance.Another large survey of ourpatient isolates was performed in Ontario in 1988.revealing relative penicillin resistance (MIC 0 .12 ~g/mL to 1.0 ~g/mL) in eight of 551 specimens (1.5% ) (13).The eight relatively resistant isolates were all cultured from swabs of nose, eyes, ears and throat from ch il dren .
Invasive infection v.rith penicillin-resistant pneumococci has been reported from Canada.A survey of isolates from blood or other sterile body flu ids done in Quebec from 1984-86 revealed relative penicillin resistance (MIC 0.12 to 1.0 pg/mL) in six of 468 isolates (1.3%) (14).Furthermore, individual cases of serious This infant responded well to e1ytl1romycin therapy.Finally.Kibsey (18) reported the case of a five-year-old child who developed fatal bacteremic pneumonia with a multiply resistant Strep pnewnoniae (MIC 2 pg/mL).
Pneumococci with increased resistance to bela-lac-Lam antibiotics do not produce beta-lactamase enzymes.Rather, resistance is associated with alterations in penicillin -binding proteins ( 19).Optimal treatment of infections due to these organism s depends on tl1e degree of resistance.the site of infection , and U1e pattern of resistance to alternative antibiotics (20.21).HigT 1 dose pen icillin may be adequate for infection wiU1 relatively resistant strains outside of the central nervous system (22).However.meningitis will often fail to respond to even h igh dose penicillin therapy.Therefore central nervous system infections shou ld be treated wiU1 cidal d rugs that penetrate the blood -brain barrier.chosen on U1e basis of in vitro sensitivity data.lmipenem.cefotaxime or vancomycin are likely to be effective (2.23) .
In summa1y.to date.penicillin -res istant pneumococci are unusual in Canada.The present auU1ors have reported a case ofbacteremic pneumonia in a Canadian adult caused by Strep pneumoniae with relative resistance to penicillin.The case emphasizes tl1e importance of routine sensitivity testing for clinical isolates from sterile s ites.and also emphasizes the need for continuing surveillance of pneumococci for penicillin and oU1er antibiotic res istance in Canada.

resistant bacteremic pneumonia pneu
(16)ccal disease due to relatively penicillin-resistant organism s have been reported (1 5 .1 6).To date.onlythreeinstances of h igh level penicillin resistance have been desc1ibed.Lapointe and Joncas (16 .17)reportedan infant with m en ingitis due to a resistant Strep p neu mon iae (MIC 2 .0pg/mL)successfully treated with h igh dose ampicillin.Th e same a u tho rs also described U1e case of a three-week -old Inu it female wiU1 pneumonia.inwhicha res istant pne umococcus (MIC 2.0 pg/mL) was isolated from tracheal secretions(16).
CAN J INFE CT DIS VOL 3 N o 4 JULY/AUGUST 1992 Penicillin-