INFECTIONS : DIRECTIONS FOR THE ' 90 s Interim report on drug utilization review of community acquired , nursing home acquired and nosocomial pneumonia : Clinical , bacteriological and radiological spectrum

OBJECTIVES: To review the epidemiology of community acquired, nursing home acquired and nosocomial pneumonia in terms of clinical. bacteriological and radiological features and to examine the spectrum of and response to antimicrobial agents used in its management.

Vingt-el-un patients ( 1.5 %) onl mis fin a lcur lraitemenl con t.re l'avis medical cl 320 (25 %) sonl dccedes duranl lcur hospitalisation.donl 165 porlaienl la mention de pneumonie comme cause du deccs au certi fic al de cleces.CONCLUSIONS : La pncumonie clemeure une malaclie grave qui s•accompagne de Laux de morbidile ct de morlalile elcvcs.Ccux qui en souffrent cl qui rcquicrenl une hospitalisation sonl ages elgravcmen l malacles.Les palhogenes Jes plus frequents en general sont toujours S. pneumoniae el /-/.injluenzae.bicn que les organismes a Gram negalif ct S. aureus aienl egalemenl cle largemenl represenlcs dans Jes cas de pneumonie nosocomiale el acquise en foyer.Le pourccnlage eleve cl'infection Gram negative clans le groupe de pneumonie exlra-hospilaliere n'a pas etc clccrit.prccedemment cl pounail representer un changcmenl clans !'expression des palhogenes qui affeclent cc groupe.Trois des 53 cas de pncumonie exlra-hospitalicrc.chez qui P. aeruginosa avail ele identifie, onl ele ou la thoracocentese.II scmble quc le mode actucl de traitement anlim icrobicn soil approprie pour trniter la pneumonie, compte tenu du foncUonnemenl des palhogcncs en cause.Dans la presenle elude.l"cmploi pragmalique de ceflriaxone a raison de l g/24 h chez ces malades a scmble donner des rcsullals lhcrapcutiqucs semblablcs a ccux d"autres traitemcnls d"associalion.D ESPITETI IE ADVENT OF EFFECTIVE ANTIMI C ROBIAL AGENTS and increasingly better understanding of t.he pathogenesis and etiology of pneumonia.morbidity and mortality remain high .Accurate assessment of lhe overall burden of pneumonia on healU1 care cannot.be ascertained because a significant.percentage of pneumonia is managed on an out-patient basis.However, statistics from lhe Unit.eelSt.at.es suggest.lhat.over 3.3 million cases of community acquired pneumonia (CAP) occur annually (1).Alt.hough mortality is low in the out-patient.selling.it.is lhe fifth leading cause in !.hose over 65 years of age in lhe United States (2).Morla.lily is usually 25% in ll1ose requiring hospitalization.wit.11 highest mortality in cases where intensive care unit.(1cu) admission is required (3)(4)(5)(6)(7)(8)(9)(10). In one sludy of 30 palients with pneumonia treated in lhe 1cu, mortality was found lo be as high as 47% (l l).In most.reports, higher morbidity and mortality were seen in the elderly (5,7 , 12). and in those wilh concurrent.illnesses such as chronic obstructive lung disease, diabetes mellilus, chronic renal failure, congestive heart.failure and chronic alcohol abuse (5.7 -9).Our current.ability to improve longevity allows patients lo develop concomitant.medical illnesses and is likely responsible for t.he lack of significant improvement.in the overall prognosis of pneumonia.In the past decade.!.here has been an increase in ll1e pool of susceptible hosls.particularly patients wit.h compromised immune defence systems.Owing this period, !.here has been a marked increase in human immunodeficiency virus disease and an increase in numbers of survivors of organ t.ransplanlation who are on chronic immunosuppressive agents.Al lhe same lime.the development.of newer and more powerful anlimicrobial agents has met.wit.haparallel emergence of resist.antand new st.rains of infecling organisms.
Recent publication of guidelines for ll1e management of CAP (l 3-15) underscores ll1c importance of continually updating our knowledge of this persist.en!. but.everchanging disease.The current.study was undertaken lo review ll1e contemporary epidemiology of CAP.nursing home acquired pneumonia (NI IAP) and nosocomial or hospital acquired pneumonia (1 IAP) in a mixed primary lo lert.iaryselt.ing.We sought.lo characterize the patient.population al risk, lhe spectrum of clinical and roentgenographic presentation.the pattern of offending pathogens and ll1e response lo current.pragmatic antimicrobial regimens used in lhe management. of pneumonia in the hospital set.ling.

PATIENTS AND METHODS
Sample population: All palienls wiU1 a diagnosis of pneumonia identified by a compu ler database of a ll discharges from ll1e Well esley Hospital, Toronto.Ontario were selected from a ret.rospeclive review of hospital charts spanning the five-year period from April 1987 to March 1992.The Wellesley Hospital is a universilybased, 400-bed hospital that funclions moslly as a primary and secondary cent.re with annual lolal hospital pat.ienl discharge of 15,000 t.o 16,000.A small port.ion of discharges originates from a t.erliary referra l base due lo proximity t.oThe Princess Marga.relHospital , the major oncology referral hospital in southern Ontario, and to the existence in our hospital of l11e only bum unit in the cily.Palienls wilh a diagnosis of Pneumocystis carinii pneumonia were excluded from lhe study.Data c ollection: Informalion was manually exlraclecl from the charts and recorded on a database sheet.before final entry inlo a computer database program.Informal.iongathered included: first, palient demographic such as age and sex; second, concurrent.medical illnesses (defined as chronic obstructive pulomary disease, asthma, past and present smoking history, diabetes mellitus, chronic renal disease, congestive heart disease, underlying malignancy, immune deficiency-bot.11primary and iatrogenic, such as long term use of immunosuppressive agents -and chronic alcohol abuse); third , laboratory findings including complete blood cell count., serum sodium, chest.roentgenogram (in the majority of cases.ll1e official radiology report was used alll1ough at times only results of ll1e handwritten chart were reliable) and microbiological tests; fourth, duration and type of antimicrobial agents used a nd presence of adverse drug react.ions;fift.11, development. of complications (defined as lung abscess, e mpyema.pleural effusion, congestive heart.failure.bacteremia a nd pneumothorax): siA'i.h.need for oxygen ll1erapy and 1cu admission; sevent.11,length of slay in hospital and in ll1e 1cu; and finally, ultimate outcome (see below  There appears lo be a slight preponderance of males (784 cases or 60%) compared with females (516 cases or 40%).Mean age was 65 years (range 16 to 103).One thousand two hundred and sixty (97%) had at least one concomitant medical condition as defined at the start of the study; of these patients, the majority had two or more concurrent medical illnesses.Of the 1300 cases of pneumonia, 806 (62%) were CAP , 116 (9%) were NHAP and 378 (29%) were HAP.The three groups were similar  in terms presence of comorbid disease although lhe patients in lhe Nll/\P group were older and fewer had a history of smoking (Table 2).Chest roentgenogram was clone on 1273 (98%) patients on admission and was abnormal in 98% of these.although a surprising 2% of patients with HAP were reported to have a normal chest roentgenogram (Table 3).Focal radiographic abnormalities were most common.Among the three groups of CAP.NI LAP and I LAP.there was no difference in rocntgenographic presentation.
Of the initial 1300 patients reviewed, 60% had positive cu ltures, ie.785 cases had positive cultures of blood.sputum.bronchoalveolar lavage fluid with or without protected brush specimen or positive serology.Streptococcus pnewnoniae (154 isolates) and Haemophilus injluenzae (147 isolates) predominated overall.The pattern of organisms detected differed in the three groups.In the CAP group, S pneumoniae.H injl.uenzae and Staphylococcus aureus were the predominant organisms.There was also a high incidence of Pseudomonas aeruginosa.a surprising finding.In the 111\P group, S aureus and Gram-negative organisms were most common.The NI IAP group showed an equal d istribution of Gran1-positive and Gram-negative organisms (Table 4).
The high incidence of Gram-negative infection in th. e CAP group was unexpected and had not been previously reported.This phenomenon is mostly due to the finding of P aeruginosa in the CAP group (53 isolates).Although 24C Antibiotics used Aminoglycoside + beta- the majority (48) were detected on cultures of sputum and bronchoalveolar lavage fluid, lliree cases were detected on blood cu ltures.Ten patients had underlying bronchiectasis or cystic fibrosis and one had an underlying hematogenous malignancy.Although these 11 patients have a higher incidence of colonization with P aeruginosa, they were also at h igher risk of developing infection due to P aeruginosa (Table 5).Two hundred and seven (16%) of the 1300 patients required 1cu admission.Ninety-six (7%) patients developed complications as defined initially.Complications of pneumonia were highest in the ILAP group, occurring in 38 (10%) of the 378 patients.The complication rate was 6% in the CAP group and 8% in the NHAP group (Table 2).
Combination therapy with antimicrobial agents with coverage for Gram-positive and Gran1-negative agents was the most common antimicrobial regimen of choice.6).
Thirteen per of patients received ceftria.xoneeither alone (l O of 169) or in combination with other antimicrobials (159 of 169).The most frequent concomitant antibiotics wilh cefl1iaxone were clindamycin and erythromycin.The mosl common indication for use of ceft.riaxone over other antimicrobial regimens was lhe presence of renal impairment.The close of ceftriaxone was 1 g/24 h in about half the patients.High dose ceft.riaxone(3 lo 4 g/24 h) was used for those with suspected meningeal infection.Out.comes in those receiving 1 g/24 h and those receiving 2 g/24 h were comparable, with mortality of 37% in both groups.Overall mortality in the group receiving ceflriaxone was 40% (67 of 169) (Table 7) .This rale was higher than thal of the group receiving 0U1er antibiotics.which was. however, a much larger group (1081 versus 169) .Differences in adverse reactions and cure rat.es (Table 8) between the groups may be partially altribulable lo the fact thal patients who received ceftria.xoneformed a preselected group, primarily sicker patients and those willi renal impairment.Previous studies have shown signillcanUy higher mortality in patients with pneumonia and renal impairment (7 . 16).
Analysis of patients in whom P aeruginosa was identified revealed lhal the majority of cases were detected on culture of sputum or bronchoalveolar lavage fluid, allliough eight of the 100 isolates were from blood  'All other antimicrobial regimens were given in the intravenous form unless otherwise stated cultures (Table 5).Morlalily in th is subgroup was high (34%).with higher morlali ly seen in lhe 11Ar and NIIAP groups (50%) .Although overall morlalily in lhe CAP group wilh positive cul lures for P aeruginosa was lower (20%) lhan the group as a whole.lhe majority (40 of 42) received antibiotics.and 10 received effective anlipseudomonal therapy wilh am inoglycoside plus bela-lactam.Seven received ceft.riaxonceither alone or in combination with olher antimicrobials.Patient outcome in lhe different lreatmenl groups was compared (Table 7).Palienls who received monotherapy with s ingle agents had beller survival rates compared with the group as a whole.Patients receiving erylhromycin, eiU1er oral or parenteral.had a survival rale of 95% (52 of 55) .Those treated wit.h cefuroxime or ampicillin had survival rat.es of 81 and 80%.respectively.The worsl survival rates were seen in palienls treated with clindamycin and genlamycin (45%) and in those receiving no therapy al al l (54%).
In all, 959 (73%) patients were deemed lo have improved or been cured al the Lime of discharge.Twenty-one (1.5%) patients d ischarged themselves against medical advice and were presumed lo have survived.Three hundred and twenty (25%) palienls died during admission to hospital; of these, 165 deaths could be altribuled lo pneumonia on review of the death certillcale.

26C
Although a higher incidence of Gram-negative organisms is found in NHAP and HAP, S aureus is also a significant causative organism in these two subgroups.These findings are consistent.with other reports of nosocomial pneumonia (17)(18)(19)(20)(21)(22)(23)(24).The different mortality rates seen in association with the different antimicrobial regimens likely represent the severity of illness rather than the efficacy of the different treatment modali1.ies.ll is certain ly reasonable to assume that patients treated with erythromycin, cefuroxime or ampicillin alone represented those who were clinically more st.able,whereas I.hose receiving combination therapy, particular combinations that included anaerobic and / or Gram-negative coverage.were more ill.These were likely patients with risk factors for aspiration or having serious comorbid disease.
Most reports of microbiological investigations in the management of pneumonia have found a utility in I.he range of 50%.Although we have not.improved the yield of our investigations to identify the offending pathogen, routine cultures of sputum, blood in all patients requiring hospitalization and in select cases, bronchoalveolar lavage fluid.serological specimens and pleural fluid should be sent.Because antimicrobial agents are begun empil;cally in the majority of cases, these relatively inexpensive and simple investigations may help lo narrow the spectrum of antibiotics used and improve I.he precision of management.Furthermore, knowledge of culture and sensitivities may guide appropriate choice of oral step-down therapy.
Mortality directly attributed to pneumonia was 13% (165 of 1300).Overall mortality in our study is 25% and appears unchanged from previous reports.However.this population is sicker.They have more concomitant illnesses than previous groups that.have been described.Cases of pneumonia managed in I.he out-patient set.ting are logistically difficult to study but one can logically assume that these patients have a better outcome than their counterparts who require hospitalization.In this study.mortality is similar to that described in previous studies in which the patient populations were less ill (3-10).Therefore, it.is possible that our current.ability to manage this persistent illness is improving.Given lhe pallem of causative agents seen in our study, it appears that monolherapy with ampicillin, e1ythromycin or cefurox:ime in the relatively well CAP group is appropriate.For the sicker CAP and for the NI !AP and llAP groups, combination therapy with a bela-lactam and a Gram-negative or anaerobic agent or ceftriaxone are appropriale initial agents.A ceftriaxone dose of 1 g/24 h is comparable with the higher dose of 2 g/day and should be used.ErytJ1romycin is particularly appropriate as an initial agent in cases where M pneumoniae Legionella pneumophila is suspected or where it is more prevalent.
Although our sludy is retrospective and therefore has many of the problems associated with these types of studies.its strength resides in U1e large number of palienls and ils current setting.The most recent large scale published reports (4.5) of CAP ended in 1987 and had considerably fewer patients lhan the current study, which began in 1987.
It is important lo update periodically our knowledge of the epidemiology and pathogenesis of pneumonia for several reasons.The eme rgence of res islanl organisms and the rapid development of new antimicrob ia l agenls can quickly outdale our current management.In addition, a rational approach lo choice of emp iri cal agents used requires up lo dale knowledge of the pattern of offend ing organisms and the population at risk.This study supports our current approach lo the managemenl and lrealmenl of CAP.NIIAP and IIAP.

CAP
Community acquired pneumonia; HAP Hospital acquired pneumonia; NHAP Nursing home acquired pneumonia CAN J INFECT DIS VOL 5 SUPPL C AUGUST 1994 Drug utiliza tion review Our five -year review of all patients discharged with a diagnosis of pneumonia from hospital from April 1987 lo March 1992 contains the most recent comprehensive data available.Data from the initial 1300 of 1782 cases 25C CHow eta! us Y•DONOTCGn CAN J INFECT DIS VOL 5 SUPPL C AUGUST 1994 USE O LY• DO OT COPY Drug utilization review ). Pneumonia was considered t.o be community acquired if t.he diagnosis was made within l11e first.72 h of admission, hospital acquired if made after 72 hand nursing home acquired if ll1e patient.was a resident.of a nursing home and the diagnosis was ma de within U1 e flrsl 72 h.
Microbi ological dat a : All microbiological data were extracted from t.he official microbiology department.USE O LY• DO OT COPY

TABLE 1
Total pneumonia cases during fiscal years 1987 to 1992RESULTSDuring the five-year period (April 1987 through March 1992).therewere74,435 patient discharges from the Wellesley Hospital.One thousand seven hundred and eighty-two cases (2.6% of all discharges) had a diagnosis of pneumonia.The first.1300 of the 1782 cases identified are reported (Table1).

TABLE 4 Most common pathogens identified from cultures in 1300 patients* Total CAP NHAP HAP
•rhese results include cultures of sputum, blood, bronchoalveolar lavage and/or protected brush specimens, pleural fluid and serology.CAP Community acquired pneumonia; HAP Hospital acquired pneumonia; NHAP home pneumonia

TABLE 8 Outcome and adverse drug reaction in the different treatment groups
The current data are likely a reflection of the I.rend to treat.more patients in an ambulat01y setting.Since studies have shown that patients with pneumonia and concurrent illness have more severe disease (8,9), it.is reasonable to assume that.those admitted t.o hospital represent the sicker end of the spectrum.
(80% versus 75%).With a trend towards increased ambulatory patient management, those with CAP requiring hospitalization over the past.several years are likely sicker and have more comorbid illness than those managed as out-patients.Our data likely reflect a change in the pattern of pathogens affecting this subpopulation with CAP.