AND
0066-4804/87/060876-07$02.O0/O
Copyright C 1987, American Society for Microbiology
One hundred seven patients with community-acquired pneumonia thought to be of bacterial etiology by the
admitting physician but whose initial sputum Gram stain was inadequate to direct specific therapy were
randomized to receive either intravenous ampicillin or cefamandole as empiric therapy. Patients were excluded
if the initial sputum Gram stain was highly suggestive of infection with Streptococcus pneumoniae, Staphylococcus aureus, or an enteric gram-negative bacillus. The two study groups had comparable demographic and
presenting clinical features. The mean age of the patients evaluable for determination of clinical efficacy was
69 years, and >75% had at least one serious underlying medical disorder. In the 90 evaluable patients, there
were 11 therapeutic failures (12%), including 5 deaths (5%). Cefamandole, a broad-spectrum antibiotic, was
not more efficacious than ampiciHlin in producing a satisfactory clinical response or in shortening the duration
of parenteral therapy. Patients received an average of only 4 days of intravenous antibiotics before changeover
to oral therapy and were hospitalized for a mean of 7 days. No patient experienced a relapse of pneumonia
following successful completion of parenteral drug therapy. We conclude that cefamandole is not a more
effective agent than ampicillin for empiric therapy of community-acquired bacterial pneumonia of uncertain
etiology.
interest in using a broader-spectrum agent, such as cefamandole. Since broad-spectrum agents are more expensive than
ampicillin, it would be useful to document the clinical value
of using a broader-spectrum agent during empiric therapy of
pneumonia. Accordingly, this study was undertaken to compare the safety and efficacy of ampicillin versus cefamandole
in a prospective double-blind fashion as empiric therapy for
patients hospitalized for treatment of community-acquired
presumed bacterial pneumonia.
(This research was presented at the 25th Interscience
Conference on Antimicrobial Agents and Chemotherapy
[D. J. Weber, S. B. Calderwood, A. W. Karchmer, and
J. E. Pennington, Program Abstr. 25th Intersci. Conf. Antimicrob. Agents Chemother., abstr. no. 893, 1985].)
*
Corresponding author.
t Present address: Infectious Disease Division 229H, University
for
reasons
877
independent samples.
RESULTS
Characteristics of study group and bacteriologic evaluation.
One hundred seven patients were randomized to receive
either intravenous ampicillin or cefamandole; 90 patients
were evaluable for clinical efficacy (Table 1). Evaluable
patients in the ampicillin and cefamandole groups were
comparable in demographic features and presenting clinical
and laboratory findings.
An initial expectorated sputum sample was obtained in 85
evaluable patients (94%) (Table 1). A potential bacterial
pathogen was identified in purulent sputum from 40 of these
85 patients (47%). In the remainder, only normal respiratory
flora were recovered by culture; while some of this latter
878
WEBER ET AL.
TABLE 1. Characteristics and presenting features of patients evaluable for clinical efficacy
Cefamandole
Ampicillin
Characteristic/feature
54
53
Total patients randomized
6
11
Unevaluable for clinical efficacy
48
42
Evaluable for clinical efficacy
Significancea
NS
Demographics
Male: female (no.)
Age (yr)
Wt (kg)
30:12
68.8 16.9
65.3 11.8
29:19
68.9 + 15.3
69.1 t 20.0
NS
NS
NS
Presentation
Days symptomatic, median (first, third quartile)
Admission temp (C)
NS
Underlying diseases
Patients with pulmonary diseases (no.)b
Asthma
Chronic obstructive lung disease
Restrictive lung disease
Patients with other disorders (no.)b
Ethanol abuse
Congestive heart failure
Diabetes mellitus
Cancer in remission
Neurologic impairmentc
Patients with at least one underlying disease (no.)
18 (43%)
5
15
2
25 (60%)
5
6
5
6
10
33 (77%)
17 (35%)
3
15
1
24 (57%)
7
4
8
4
8
36 (75%)
NS
34:8
15.0 5.9
32:9
1.3 0.6
41:7
13.3 5.1
36:9
1.3 0.5
NS
NS
NS
NS
8
7
1
1
4
19
2
11
8
0
0
0
26
3
Laboratory findings
Chest radiograph, infiltrate-one lobe: multilobar
Leukocyte count (1,000/mm3)
Bands, <15%.: >15%d
Creatinine (mg/dl)
Initial sputum culture (no. of patients)
Streptococcus pneumoniae
Haemophilus influenzae
Staphylococcus aureus
Escherichia coli
Mixed pathogens
Normal flora only
Sputum not obtained
NS
NS
879
Ampicillin
Cefamandole
Significancea
42
37:5
48
42:6
NS
2
3
0
14.9 + 5.4
3.7 1.4
1 (<1, 2)
7.1 + 6.2 (5)
3
2
1
17.0 8.8
4.2 2.2
2 (<1, 3)
7.4 + 4.2 (6)
NS
NS
NS
Ampicillin
8.8
2.7
Cefamandole
8.6
27
4
3
3
20
13
3
6
34
1
0
2
36
2
3
1
28
Improved
Unavailable
Late superinfection
a Not significant; P > 0.10.
33
0
6
3.5
880
WEBER ET AL.
presented with superinfection 2 to 3 days following completion of their oral antibiotics. One patient presented with H.
influenzae (beta-lactamase negative) tracheobronchitis, one
presented with a Pseudomonas maltophilia (ampicillin and
cefamandole resistant) pneumonia, and the final patient, who
had received only 5 days of antibiotics, developed a new
pulmonary infiltrate of unknown etiology.
DISCUSSION
Our study group was not designed to evaluate the etiology
of community-acquired pneumonia but rather to compare
two antibiotic regimens for empiric therapy of suspected
bacterial pneumonia. We excluded patients in whom the
Gram stain of initial sputum was thought by the admitting
physician to be highly suggestive of infection due to Streptococcus pneumoniae, Staphylococcus aureus, or an enteric
gram-negative bacillus since these patients should receive
specific antimicrobial therapy. We focused instead on the
large group of patients admitted to a hospital for antibiotic
therapy of presumed bacterial pneumonia of uncertain etiology. We also included patients in whom initial sputum Gram
stains suggested infection with H. influenzae, as either
ampicillin or cefamandole is commonly used in this situation.
The demographic makeup and presenting clinical and
laboratory features of our study group were similar to
previous reports of patients hospitalized with pneumonia,
except that our patients were somewhat older (5, 9, 14, 15,
18, 36, 40, 46, 56, 61). Of note was a 75% overall frequency
of underlying diseases known to predispose to pneumonia.
Thus, our study group may be considered a high-risk patient
population.
The etiology of pneumonia remained uncertain in over
one-half of the patients in our study. These were the patients
who were unable to produce an adequate sputum sample
uncontaminated with oral secretions, a common problem in
clinical practice. All of these patients, however, were felt to
have acute bacterial pneumonia by the admitting physician
and to require empiric antibiotic therapy. Of the patients in
this group who failed therapy with one of the study drugs,
only one was subsequently discovered to have an atypical
pneumonia, mycoplasma, despite extensive serologic and
invasive workup. In 40 patients, a presumed bacterial pathogen was isolated from sputum culture that correlated with
interpretation of sputum Gram stains when reviewed by one
of the investigators. In most of these patients, reading of the
initial sputum Gram stain by the admitting physician was
confounded by small amounts of contamination with respiratory tract flora, inability to obtain sputum during the first
several hours of hospitalization, or misinterpretation of the
organisms present. As in similar series, the most common
Six percent of our patients died, often from causes unrelated to respiratory insufficiency or sepsis. Several other
antibiotic trials of patients hospitalized with communityacquired respiratory infections have reported mortality rates
ranging from 4 to 11% and have noted that most deaths
resulted from the patients' underlying disorders (10, 20, 22,
25, 26, 31, 53, 58). The mortality rate for our patients is lower
than the 8 to 24% reported for patients hospitalized with
community-acquired pneumonia but not specifically entered
in a therapeutic trial (14, 15, 21, 40, 46, 61, 66). This
difference may reflect the fact that antibiotic trials, including
ours, often exclude patients with immunosuppression or
neutropenia or those who are severely ill and unable to give
informed consent. Our overall response rate of 88% is
similar to that reported in previous trials that used cefamandole alone for the treatment of lower respiratory tract
infections (26, 41, 42, 44, 53) or in comparison with cefotiam
(6), ceftizoxime (25, 35, 39, 58), cefonicid (24, 65), ceftazidime (16, 31), or cefoperazone (20).
The patient groups randomized to ampicillin and cefamandole therapy were comparable with regard to demographic,
clinical, laboratory, and radiographic characteristics on admission. Despite the inclusion of numerous elderly and
high-risk patients, cefamandole did not prove more efficacious than ampicillin when used as empiric therapy for
patients hospitalized with presumed bacterial pneumonia.
Side effects and superinfections were infrequent, and their
incidence did not differ between the ampicillin and cefamandole groups. Previous antibiotic trials have demonstrated
that cefamandole is as efficacious as penicillin for pneumococcal pneumonia (54, 55) and as efficacious as ampicillin for
lower respiratory infection due to H. influenzae (10). Further, broad-spectrum cephalosporins have not been shown
to be more efficacious than cefamandole for communityacquired pneumonia (6, 16, 20, 24, 25, 31, 35, 39, 58, 65).
Thus, cost considerations appear to favor the empiric use of
ampicillin over cefamandole for the majority of patients
hospitalized with presumed bacterial pneumonia of uncertain etiology. However, cefamandole or another broadspectrum antibiotic may be desirable as an initial empiric
agent in patient subgroups known to be at high risk for
infection due to Staphylococcus aureus or gram-negative
bacilli. These groups might include presumed bacterial pneumonia following viral influenza, patients cared for in extended-care facilities, neutropenic or immunosuppressed patients, or patients readmitted after recent hospitalization.
The rapid defervescence noted in our patients and the
relatively short duration of intravenous antibiotics used for
adequate clinical response (4 days) are worthy of comment.
Despite the older age of our patients and the high frequency
of concurrent serious medical and pulmonary disorders,
patients were hospitalized an average of only 7 days. No
patient who met our criteria for a successful response to
parenteral study drug subsequently developed a relapse of
pneumonia after a change to oral antibiotic or in the follow-up period. Only three patients, all in the cefamandole
group, developed superinfection following combined intravenous and oral antibiotic therapy.
We conclude that (i) cefamandole is not more effective
than ampicillin as initial empiric therapy in patients hospitalized with presumed bacterial pneumonia whose Gramstained sputum smear is inadequate to direct specific therapy
and (ii) patients who respond promptly to treatment with
intravenous antibiotics may often be switched to oral antibiotic therapy as early as 3 to 4 days after admission, without
significant risk of relapse of their pneumonia. Treatment of
the majority of patients with uncomplicated communityacquired bacterial pneumonia does not require an extended
period of intravenous antibiotics.
ACKNOWLEDGMENTS
We gratefully acknowledge the assistance of the houie staff and
private physicians at the participating institutions in identifying and
entering patients into this study. Ronald Romnard of Massachusetts
General Hospital, Paul Sesin of New England Deaconess Hospital,
and Kathleen Benfell of Brigham and Women's Hospital provided
expert help in carrying out the double-blind randomization protocol.
Linda Krilov assisted in data collection.
This work was supported by Eli Lilly & Co., Indianapolis, Ind.
LITERATURE CITED
1. Anhalt, J. P., L. D. Sabath, and A. L. Barry. 1980. Special tests:
bactericidal activity, activity of antimicrobials in combinations,
and detection of beta-lactamase production, p. 478-484. In
E. H. Lennette, A. Balows, W. J. Hausler, Jr., and J. P. Truant
(ed.), Manual of clinical microbiology, 3rd ed. American Society for Microbiology, Washington, D.C.
2. Barry, A. L., and C. Thornsberry. 1980. Susceptibility testing:
diffusion test procedures, p. 463-474. In E. H. Lennette, A.
Balows, W. J. Hausler, Jr., and J. P. Truant (ed.), Manual of
clinical microbiology, 3rd ed. American Society for Microbiology, Washington, D.C.
3. Bentley, D. W. 1984. Bacterial pneumonia in the elderly: clinical
features, diagnosis, etiology, and treatment. Gerontology 30:
297-307.
4. Berk, S. L., S. A. Holtsclaw, A. Kahn, and J. K. Smith. 1981.
Transtracheal aspiration in the severely ill elderly patient with
bacterial pneumonia. J. Am. Geriatr. Soc. 29:228-231.
5. Berntsson, E., J. Blomberg, T. Lagergard, and B. Trollfors.
1985. Etiology of community-acquired pneumonia in patients
requiring hospitalization. Eur. J. Clin. Microbiol. 4:268-272.
6. Beumer, H. M., W. P. Olislagers, M. Kahn, and J. D. van
Hamersveld. 1985. Clinical evaluation of cefotiam and cefamandole in respiratory tract infections. Int. J. Clin. Pharmacol.
Ther. Toxicol. 23:105-108.
7. Campos, J., S. Garcia-Tornel, and I. Sanfeliu. 1984. Susceptibility studies of multiply resistant Haemophilus influentzae isolated from pediatric patients and contacts. Antimicrob. Agents
Chemother. 25:706-709.
8. Crane, L. R., and A. M. Lerner. 1983. Gram-negative bacillary
pneumonia, p. 227-250. In J. E. Pennington (ed.), Respiratory
infections: diagnosis and management. Raven Press, New York.
9. Crofton, J. 1970. The chemotherapy of bacterial respiratory
infections. Am. Rev. Respir. Dis. 101:841-859.
10. Delgado, D. G., C. J. Brau, C. G. Cobbs, and W. E. Dismukes.
1979. Clinical and laboratory evaluation of cefamandole in the
therapy of Haemophilus spp. bronchopulmonary infections.
Antimicrob. Agents Chemother. 15:807-812.
11. Doern, G. V., J. H. Jorgensen, C. Thornsberry, D. A. Preston,
and the Haemophilus influenzae Surveillance Group. 1986. Prevalence of antimicrobial resistance among clinical isolates of
Haemophilus influenzae: a collaborative study. Diagn. Microbiol. Infect. Dis. 4:95-107.
12. Donowitz, G. R., and G. L. Mandell. 1983. Empiric therapy for
pneumonia. Rev. Infect. Dis. 5(Suppl.):40-51.
13. Donowitz, G. R., and G. L. Mandeil. 1985. Acute pneumonia, p.
394-404. In G. L. Mandell, R. G. Douglas, Jr., and J. E.
Bennett (ed.), Principles and practices of infectious diseases.
John Wiley & Sons, Inc., New York.
14. Dorff, G. J., M. W. Rytel, S. G. Farmer, and G. Scanlon. 1973.
Etiologies and characteristic features of pneumonias in a municipal hospital. Am. J. Med. Sci. 266:349-358.
15. Ebright, J. R., and M. W. Rytel. 1980. Bacterial pneumonia in
the elderly. J. Am. Geriatr. Soc. 28:220-223.
16. Engle, J. C., P. W. Lifland, and C. J. Schleupner. 1985.
Comparison of ceftazidime with cefamandole for therapy of
community-acquired pneumonia. Antimicrob. Agents Chemother. 28:146-148.
881
6B):32-37.
23. Gavan, T. L., and A. L. Barry. 1980. Microdilution test procedures, p. 459-462. In E. H. Lennette, A. Balows, W. J.
Hausler, Jr., and J. P. Truant (ed.), Manual of clinical microbiology, 3rd ed. American Society for Microbiology, Washington,
D.C.
24. Geckler, R. W., G. D. McCormack, and J. S. Goodman. 1984.
Comparison of cefonicid and cefamandole for the treatment of
community-acquired infections of the lower respiratory tract.
Rev. Infect. Dis. 6(Suppl. 4):847-852.
25. Grieco, M. M., M. Lange, J. A. Daniels, M. Den, N. Atnaram,
and H. Kornfeld. 1982. Single-blind controlled study of
ceftizoxime and cefamandole in the treatment of communityacquired pneumonia. J. Antimicrob. Chemother. 10(Suppl.
C):223-225.
26. Hoverman, I. V., and L. 0. Gentry. 1978. Cefamandole nafate in
the treatment of acute bacterial pneumonia. Curr. Ther. Res.
24:622-629.
27. Isenberg, H. D., J. A. Washington II, A. Balows, and A. C.
Sonnenwirth. 1980. Collection, handling, and processing of
specimens, p. 52-82. In E. H. Lennette, A. Balows, W. J.
Hausler, Jr., and J. P. Truant (ed.), Manual of clinical microbiology, 3rd ed. American Society for Microbiology, Washington,
D.C.
28. Joyce, S. M. 1985. Transtracheal aspiration, p. 80-83. In J. R.
Roberts and J. R. Hedges (ed.), Clinical procedures in emergency medicine. The W. B. Saunders Co., Philadelphia.
29. Kalinske, R. W., R. H. Parker, D. Brandt, and P. D. Hoeprich.
1967. Diagnostic usefulness and safety of transtracheal aspiration. N. Engl. J. Med. 276:604-608.
30. Karnad, A., A. Salvador, and S. L. Berk. 1985. Pneumonia
caused by gram-negative bacilli. Am. J. Med. 79(Suppl.
1A):61-67.
31. Keeton, G. R., B. Kehoe, S. W. Phillips, and H. Daya. 1983.
Ceftazidime and cefamandole in the treatment of pneumonia. J.
Antimicrob. Chemother. 12(Suppl. A):27-30.
32. Kilian, M. 1980. Haemophilus, p. 330-336. In E. H. Lennette,
A. Balows, W. J. Hausler, Jr., and J. P. Truant (ed.), Manual of
clinical microbiology, 3rd ed. American Society for Microbiology, Washington, D.C.
33. Klimek, J. J., E. Ajemian, S. Fontecchio, J. Gracewski, B.
Klemas, and L. Jimenez. 1983. Community-acquired pneumonia
requiring admission to hospital. Am. J. Infect. Control 11:79-82.
34. La Force, F. M. 1985. Community-acquired lower respiratory
tract infections. Am. J. Med. 78(Suppl. 6B):52-57.
35. LaFrock, J. L., A. Molavi, A. L. Lentnek, K. V. I. Rolston, P. H.
Chandrasekar, B. R. Smith, W. Kannangara, R. F. Schell, S. S.
Oakes, and B. B. Carr. 1982. Comparative study of ceftizoxime
and cefamandole in the treatment of bronchopulmonary infections. J. Antimicrob. Chemother. 10(Suppl. C):215-221.
36. Larsen, R. A., and J. A. Jacobson. 1984. Diagnosis of community-acquired pneumonia: experience of a community hospital.
Compr. Ther. 10:20-25.
37. Lode, H. 1986. Initial therapy of pneumonia. Am. J. Med.
882
WEBER ET AL.
80(Suppl. 5C):70-74.
38. Louria, D. B., H. L. Blumenfeld, J. T. Ellis, E. D. Kilbourne, and
D. E. Rogers. 1959. Studies on influenza in the pandemic of
1957-1958. II. Pulmonary complications of influenza. J. Clin.
Invest. 38:213-265.
39. Lyons, R. W., S. M. Brock, and B. Lahiri. 1982. Ceftizoxime
and cefamandole in adult patients with acute respiratory failure.
J. Antimicrob. Chemother. 10(Suppl. C):227-228.
40. MacFaIrlane, J. T., R. G. Finch, M. J. Ward, and A. D. MacRae.
1982. Hospital study of adult community-acquired pneumonia.
Lancet ii:255-258.
41. Mandell, G. L. 1980. Cefamandole treatment of pulmonary
infection caused by gram-negative rods. Scand. J. Infect. Dis.
Suppl. 25:107-111.
42. Mattson, K., O.-V. Renkonen, A. Kohvakka, and H. Kikitalo.
1980. Clinical experience with cefamandole in pneumonia.
Scand. J. Infect. Dis. Suppl. 25:103-106.
43. McKellar, P. P. 1985. Treatment of community-acquired pneumonia. Am. J. Med. 79(Suppl. 2A):25-31.
44. Meyers, B. R., G. Wormser, G. Gartenberg, P. Nicholas, and
S. Z. Hirschman. 1978. Cefamandole: a new cephalosporin for
therapy of hospitalized patients with infection. Mt. Sinai J.
Med. 45:722-728.
45. Morella, J. A., and M. Bohnhoff. 1980. Neisseria and
Branhamella, p. 111-130. In E. H. Lennette, A. Balows, W. J.
Hausler, Jr., and J. P. Truant (ed.), Manual of clinical microbiology, 3rd ed. American Society for Microbiology, Washington,
D.C.
46. Mufson, M. A., V. Chang, V. Gill, S. C. Wood, M. J. Romansky,
and R, M. Chanock. 1967. The roles of viruses, mycoplasmas
and bacteria in acute pneumonia in civilian adults. Am. J.
Epidemiol. 86:526-544.
47. Murray, P. R., and J. A. Washington II. 1975. Microscopic and
bacteriologic analysis of expectorated sputum. Mayo Clin.
Proc. 50:339-344.
48. Musher, D. M., K. R. Kubitschek, J. Crennan, and R. E.
Baughn. 1983. Pneumonia and acute febrile tracheobronchitis
due to Haemophilus influenzae. Ann. Intern. Med. 99:444 450.
49. National Center for Health Statistics. 1984. Vital statistics of
United States. 1979. National. Center for Health Statistics,
Hyattsville, Md.
50. National Committee for Clinical Laboratory Standards. 1972.
Performance standards for clinical laboratory standards. Approved standard. National Committee for Clinical Laboratory
Standards, Villanova, Pa.
51. National Committee for Clinical Laboratory Standards. 1981.
Performance standards for antimicrobial disc susceptibility
tests. Approved standard ASM-2, vol. 2, no. 2. National Committee for Clinical Laboratory Standards, Villanova, Pa.
52. Pennington, J. E. 1983. Community-acquired pneumonia and
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
acute bronchitis, p. 125-134. In J. E. Pennington (ed.), Respiratory infections: diagnosis and management. Raven Press,
New York.
Perlino, C. A., and M. E. Plaut. 1977. Cefamandole treatment of
bacterial pneumonia. Curr. Ther. Res. 22:807-813.
Petty, B. G., C. R. Smith, J. C. Wade, G. L. Conrad, J. J.
Lipsky, J. J. Ellner, and P. S. Lietman. 1978. Double-blind
comparison of cefamandole and penicillin in pneumococcak
pneumonia. Antimicrob. Agents Chemother. 14:13-16.
Plaut, M. E., and C. A. Perlino. 1978. Cefamandole vs. procaine
penicillin for treatment of pneumonia due to Streptococcus
pneumoniae: a random trial. J. Infect. Dis. 117(Suppl.):133-138.
Prout, S., P. D. Potgieter, A. A. Forder, J. W. Moodie, and J.
Matthews. 1983. Acute community-acquired pneumonia. S. Afr.
Med. J. 64:443-446.
Rein, M. F., J. M. Gwaltney, W. M. O'Brien, R. H. Jennings,
and G. L. Mandell. 1978. Accuracy of Gram's stain in identifying pneumococci in sputum. J. Am. Med. Assoc. 239:26712673.
Rodriguez, J., G. J. Vazquez, R. H. Bermudez, A. Luina, and
C. H. R. Ronda. 1982. A randomnized clinical trial of ceftizoxime
and cefamandole in the treatment of serious lower respiratory
tract infections. J. Antimicrob. Chemother. 10(Suppl. C):
209-213.
Saginur, R., and J. G. Bartlett. 1980. Antimicrobial drug susceptibility of respiratory isolates of Hemophilus influenzae from
adults. Am. Rev. Respir. Dis. 122:61-63.
Schwartzmann, S. W., J. L. Adler, R. J. Sullivan, and W. M.
Marine. 1971. Bacterial pneumonia during the Hong Kong
influenza epidemic of 1968-1969. Experience in a city-county
hospital. Arch. Intern. Med. 127:1037-1041.
Sullivan, R. J., W. B. Dowdle, W. M. Marine, and J. C.
Hierholzer. 1972. Adult pneumonia in a general hospital. Arch.
Intern. Med. 129:935-942.
Thorsteinsson, S. B., D. M. Musher, and T. Fagan. 1975. The
diagnostic value of sputum culture in acute pneumonia. J. Am.
Med. Assoc. 233:894-895.
Verghese, A., and S. Berk. 1983. Bacterial pneumonia in the
elderly. Medicine (Baltimore) 62:271-285.
Wallace, R. J., Jr., D. M. Musher, and R. R. Martin. 1978.
Haemophilus influenzae pneumonia in adults. Am. J. Med.
64:87-93.
Wallace, R. J., Jr., S. L. Niefield, S. Waters, B. Waters, R. J.
Awe, K. Wiss, R. R. Martin, and S. B. Greenberg. 1982. Comparative trial of cefonicid and cefamandole in the therapy of
community-acquired pneumonia. Antimicrob. Agents Chemother. 21:231-235.
White, R. J., A. D. Blainey, K. J. Harrison, and S. K. R. Clarke.
1982. Causes of pneumonia presenting to a district general
hospital. Thorax 36:566-570.