Community-Acquired Pneumonia (CAP) remains a considerable problem in terms of morbidity, mortality and use of hospital resources despite the remarkable advances in antibiotic therapy. This study describes the changes in the pattern of pneumonias, as manifested by new diseases, new modes of transmission and new manifestations of old diseases.peer-reviewe

Fenech, Frederick F.

Montefort, Stephen

English

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Maltese Medical Journal 47 Volume IT Issue II '90(91 COMMUNITY-ACQUIRED PNEUMONIA What is new in aetiology and treatment Stephen Monifort, Frederick F. F enech Community-acquired pneumonia (CAP) remains a considerable problem in terms of morbidity, mortality and use of hospital resources despite the remarkable advances in antibiotic therapy. It is estimated that in the u.K. 1 per HXX> in the general population is admitted with pneumonia annually (1) and pneumonia xcounts for about 10 times as many deaths (in U.K.) as all other infections combined (1). The mortality in published series has ranged from 6.7 - 18% in the British series (1) and 6-24% in the U.S.A, (1). These percentages change according to the organism causing the pneumonia and the age of the patient The past 20 years have been marked by striking changes in the pattern of pneumonias, a<; manifested by new diseases, new modes of transmission and new manifestations of old diseases. In Malta IDeumonia is also a common cause of hospital admission and we are at the moment carrying out a study to determine the frequency and the clinical pattern of the disease loca1Iy. Hospital cases are however only part of the total incidence of CAP as many cases are treated at home and never reach hospital. In fxt the incidence of CAP is unknown but estimates vary between 1-10 per 1(XX) of the population, (2,3) In the evaluation of a patient with pneumonia, the usual histo- pathological cla<;sification is of little value to the clinician. Indeed, having made the diagnosis, the major consideration is to interpret the clinical setting in which the pneumonia occurs in order to infer from this the most likely aetiological diagnosis, To do this one has to have some idea of common aetiological agents in the community as well as determine the condition of the host and the environment in which the pneumonia develops. Table 1 (1-7) summarises the aetiological frequencies of CAP in various studies reported over a 15 year period. There is a high incidence of unidentified causative micro organisms, probably due to antibiotics given prior to hospital admission, masking the infective organisms when sputum culture is attempted. In fact when other tests like counter immuno-electrophoresis (CIE) were carried out, (5), only in 2 to 4% of cases was the causative organism undetected. Strep. pneumonia was still the most common cause in almost all the series even though there was an increasing incidence of viral and mycoplasmal pncumonias, Mycoplasma, which Ixks a cell wall, occurs usually in epidemics which occur at intervals of 4-5 years. LegionelIa pneumophilia is also increasing in frequency. It is therefore important to monitor the pattern of aetiologies of pneumonias at regular intervals, as the frequency of various agents changes over the years. In a study from Yale (8), the changing pattern of causes of pneumonia between 1%9 to 1972 and 1979 to 1982 were comJXlfed. Table 2 showed that there was a decrease in bacterial causes from 63% to 48% as well as an increase in fungal and viral causes, These changes in incidence reflect changes in the pattern of medical practice over the years where there is an increase in patients with some degree of immunosuppression either because of the nature of the disease or as part of the therapy (9). S. MONTFORT MD MRCP(UK) F.F. FENECII MD FRCPG .1KPE n~cp FACP DEPT. OF MEDICINE, sr. LUKE'S HOSPlfAL TABLE 1 AETIOLOGIES OF COMMUNfTY-ACOUIRED PNEUMONIA 1971-1987 Author No of % % Viral or % % % % % % Patients Unknown Mycoplasma S Pneum. S Aureus H Inftu. Gram Neg .Legionella OTHER FEKETY 100 29 5 62 2 1971 SULLlVAN 292 36 7 35 6 5 11 1972 WHITE 210 52 29 11 4 2 1.5 1.5 4 1981 MACFARLANE 127 2.4 11 76 2.4 3 0.8 15 5.5 1982 McNABB 80 36 6.25 56 3.75 6.25 1.25 1.25 3.25 1984 MARRIE 301 34 20.3 8.6 4.6 6.3 2 3.9 20 1987 BTC STUDY 453 33 25 34 6 2 7 1987 Maltese Medical Journal 48 Volume IT Issue II '90(91 TABLE 2 INFECTIOUS PNEUMONIAS IN HOSPITALISED PATIENTS: THE CHANGING SPECTRUM AT THE YALE NEW HAVEN MEDICAL CENTRE Pathogenic Agents July 1969 to July 1979 to Isolated Jan.1972 (%) Jan. 1982 (%) Total bacterial causes 63.8% 48.6% Tolal fungal 7.2% 13.2% Total viral 17.5% 32.9% Total Patients Reviewed 935 1,175 (FICK R.B. et, THE AMERICA JOURNAL OF MEDICINE, 1983, 74,2) TABLE 3 CATEGORIES OF PATIENTS WITH PNEUMONIA TYPE I - PNEUMONIA IN A PREVIOUSLY HEALTHY PATIENT TYPE 11 - PNEUMONIA IN PREVIOUSLY UNHEALTHY LUNGS TYPE III - POST-INFLUENZAL PNEUMONIA TYPE IV - PNEUMONIA IN A COMPROMISED PATIENT TYPE V HOSPITAL ACQUIRED PNEUMONIA Table 3 shows the categories of patients in which different types of pneumonias occur in various groups of patients. This is helpful as it can give a good indication as to the likely aetiological causes of the pneumonia. The main causative agent'> of severe pneumonia in previously healthy patients, are likely to be either pneumococcal, mycoplasmal or viral. Table 4 Though the real prevalence of pneumococcal pneumonia in hospital practice is difficult to determine, becauscof pre-admission antibiotic therapy, it should still be considered as the most common cause of CAP in a previously healthy subjccL It is worrying to note that thereare emerging reports of pneumococci which are penicillin resistant (10) especially in South Africa and New Guinea where penicillin prophylaxis used to be given because of pneumococcal epidemics (11). In the last 15 years Legionella and a member of the Ol1amydia genus known as TWAR have also emerged as potential pathogens in this type of patient (12). A dramatic outbreak of pneumonia (182 cases with 29 deaths) in a Philadelphia Legionnaires convention in July 1976 led to the identification of a unique, fastidious, Gram-ve, aerobic, intracellular bacillus the following January. Retrospective studies identified this organism in cases of pneumonia occurring 25 years earlier. The commonest species (24 in all) is Legionella pneumophila and this has 12 subgroups. The incidence of Legionnaires' disease in various series of CAP ranges from 1-27%. In Malta there were some imported cases of Legionnaires' disease some of whom died. One case was in a man who had not gone abroad but the local source was not identified. Maltese sources are becoming more likely with the increasing use of air-conditioners. Legionella produces a lobar pneumonia or bronchopneumonia and can show CXR progression whilst the patient is on treatmenL An important feature is the lack of purulent sputum in the prc,,<;ence of a consolidation. Extrapulmonary involvement ranging from diarrhoea to changes in mental status may be seen in 25-75% of patients. All environmental sources of the organism are related to water and include cooling towers, condensers, humidifiers, air­conditioners, ncbulizers filled with tap water, aerosols created by showers or water fauccts. The primary method of environmental control has been 10 inerease water temperature and chlorination. The early administration of erythromycin (4g1 day IV for at least 3 weeks) _+ Rifampicin is most important as the overJ.l1 case fatality is 5-25% in previously healthy patients and up to 80% in immunocompromised patient'> (12). A newly described Chlamydia organism called 1WAR wa.<; shown 10 be the cause of 6% of pneumonias in 301 patient'> admitted to a Nova Scotia Hospital between 1981 and 1984 (7). It was the third most common cause in this study by Marrie, causing a mild pneumonia in teenagers; In patients with a pre-existing chronic lung condition, it can produce a severe illness. Its name is derived from the laboratory designation of the fIrst two isolates TW183 and AR39. It is distinct from C. trachomatis and C. psittaci and the drug of choice for its treatment is erythromycin. The diagnosis is made through micro- immunofluorescence using 1WAR as antigen. Patients with previously unhealthy lungs are susceptible to a different spectrum of organisms causing their pneumonias (Table 5). Pneumococcus together with Haemophilus influenzae is still the commonest organism causing pneumonia in chronic bronchi tics and in patients with non-cystic fibrosis bronchiectasis, while TABLE 4 LIKELY AETIOLOGICAL AGENTS OF PNEUMONIA IN PREVIOUSLY HEALTHY PATIENTS VIRUSES 	 INFLUENZA ADENO-VIRUS BACTERIA 	 PNEUMOCOCCUS LEGIONELLA MYCOPLASMA CHLAMYDIA, PSITIACI, lWAR COXIELLA BURNETI MYCO. TUBERCU.OSIS: RARE BUT LETHAL, HGHLY TREATABLE Maltese Mediml Journal 49 Volume IT Issue 11 '90(91 Finally the following therapeutic regimes TABLE 5 LIKELY AETKJLOGICAL AGENTS OF PNEUMONIA IN PATIENTS WrrH are suggested for the various types ofPREVIOUSLY UNHEALTHY LUNGS CAP. In patients who were previously healthy Erthromycin is a good choice asCOPD PATIENTS - PNEUMOCOCCUS AND NON-CYSTIC 	 HAEMOPHILUS all the common microorganisms involved FIBROSIS 	 BRANHAMELLA CATARRHALlS I including the potentially lethal Legionel\a BRONCHIECTASIS MYCOPLASMA 	 I are senslUve to it When resistance is VIRUSES 	 I encountered amoxicillin or tetracycline are good alternatives. (Table 8). CYSTIC FIBROSIS - PSEUDOtv1ONAS a PATIENTS 	 STAPHYLOCOCCUS au. In patients with previously unhealthyTABLE 6 COMMUNITY ACQUIRED PNEUMONIA IN IMMUNOSUPPRESSED lungs a different group of antibiotics PATIENTS (Table lOP) are suggested. a'> most of the organisms responsible are resistant to - PNEUMOCYSTIS C. erythromycin. A new and important - VIRAL ESPECIALLY CMV antibiotic group in this context are the 4­- FUNGI 	 - CRYPTOCOCCUS amino Quinoiones which are derivatives - CANDIDA of nalidixic acid. They are rapidly- NOCARDIA bactericidal acting on DNA gyrase (an- ZYGOMYCETES enzyme which manipulates bacterial DNA so a'> to be able to be 'packCcl' in the small - BACTERIA - GRAM-VE BACILLI bacterium); they have excellent WBC - STAPH. AUREUS and tissue compartment penetration and - MYCOBACTERIA have good bin-availability when given Pseudomonas and Staph. aureus are the The immccliate institution of treatment or<llly. There are no naturally occurring commonest micro-organisms in cystic with the most appropriate antibiotics is quino\ases and so resistance is very fibrosis patienL'>. vital if the prognosis is to be improvccl. In unlikely to occur quickly if at all. a 90- centre study with 450 patients (1) Ciprotloxacin is the best quinolone a'> Br.mhmnella catarrhalis used to he thought with CAP, there were no deaths in patienL'> regard,> the respiratory system (14) and of <L'> just a commensal but is being who received antibiotics before has a very wicle spectrum when compared inerca..,ingly rccob'l1isccl as a cause of lower hospiuliisation. It was also found that to other antibiotics. Sputum levels of respimtory trdct infcx;tion in this group of certain features predicted a worse ciprof1oxacin arc in the order of 70% of patienL'>. Thi.., is a Gmm-negative, aerobic prognosis in patienL'> with pneumonia. scrwn levels and even higher in lung diplococcus. TIle majority (50-70%) of (Table 7). Not all these features will be parenchyma greatly exeeecling the M.i.C. stmins produce B-lactmna<;es and arc thus present in the same patient but the presence of important respiratory pathogens. resisumt to penicillins but sensitive to of any of them should alert the physician Overall efficacy in chest infcx;tions is erythromycin, tetracycline or to hmpitalise the patient urgently. over 90%. Its empilical use in CAP ciprofloxacin (13). In post-influenzal TABLE 7 CLINICAL FEATURES ASSOCIATED WrrH INCREASED MORTALrrY Ipneumonias, onc must never forget iL, <L'>-'>ociation with SUlpho aureus, but again 1. AGE > 60 yearspneumex;occus is the commonest cause 2. RESPIRATORY RATE > 3D/min.of pneumonia in these patienL'>. 3. DIASTOLlC B.P. < 60 mm.Hg 4. CYANOSIS The number of immunosuppressed 5. MENTAL CONFUSION patienL, in the community today has 6. LOW Pa02 < 8 KPa increased because of drugs such as 7. VERY LOW OR VERY HIGH WBC COUNT steroici'i, organ trdm;plants, and clisc<lSCs with disturbed immunity - the best known TABLE 8 ANTIBIOTIC REGIME FOR COMMUNITY ACQUIRED PNEUMONIA IN being the acquired immunodeficiency A HEALTHY HOST syndrome (AIDS). Such pneumonias require urgent attention ,L, they carry a - PNEUMOCOCCUS worse Prob'l10Sls. - LEGIONELLA 	 ALL SENSITIVE TO ERYTHROMYCINThe aetiological agenL,> in these patienL, - MYCOPLASMAconstitute a different spectrum of micro­organisms, fungi, viruses and protozoa a'> - CHLAMYDIA causes of pneumonia. Gram-ve bacilli, staph. aurcus and mycobacteria especially - OTHER SUGGESTED ANTIBIOTICS IF MICRO-CRGANISM IS the atypical ones constitute the majority RESISTANT of the bacteria causing such infections. TETRACYCLINE (Table 6). AMOXICILLlN - -Maltese Medical Journal 50 Volume IT Issue 11 '90/91 (especially in patients with previously healthy lungs) is inadvisable in view of the ready availability of suitable alternatives, as well as the relatively poor susceptibility of pneumococcus. Aucloxacillin or amoxycillin + clavulinic acid are usually given in post-influenza! pneumonia due to the possibility of Staph. pneumonia Ciprofloxacin can also be used. In Pneumonias in immunosuppressed patients treatment must start treatment empirically without delay and changed if necessary according ID sensitivity results. Admission to hospital in such cases is mandatory. Table 10 shows recommendations of antibiotics regimes in immunosuppressed patients. These recommendations were modified from one by Masur (15). IN CONCLUSION, - Act fast in treating suspected pneumonia Though Strep.pneumonia is still the commonest cause, think of newer agents and consider host and environment in which pneumonia developed. - Though Erythromycin is still the first line drug, newer agents may be indicated. - Refer to hospital immunocompromised patients with clinical features of pneumonia. TABLE 9 ANTIBIOTIC REGIME FOR COMMUNITY ACQUIRED PNEUMONIA IN PATIENTS WITH PREVIOUSLY UNHEALTHY LUNGS AMOXICILLlN CLAVULANATE POTENTIATED AMOXCILLlN CIPROFLOXACIN CO-TRIMAXAZOLE CEPHALOSPORIN + AMINOGLYCOSIDE IN THE HOSPITAL ENVIRONMENT TABLE 10 RATlONAL ANTIMICROBIAL THERAPEUTlC REGIMENS FOR IMMUNOSUPPRESSED PATIENTS WITH EXTENSIVE PNEUMONIAS REGIMEN 	 SUSPECTED PATHOGENS LIKELY TO BE ADEOUATELY TREATED CO-TRIMOXAZOLE (high dose) OR TRIMETHOPRIM + DAPSONE PNEUMOCYSTIS C. OR PENTAMIDINE IV OR NEBULlZED ERYTHROMYCIN LEGIONELLA, MYCOPLASMA DHPG (ganciclovir) 	 CMV QUADRUPLE THERAPY 	 MYCOBACTERIA AMPHOTERICIN 	 FUNGAL INFECTION CEPHALOSPORIN 	 AEROBIC GRAM + ve COCCI AMINOGLYCOSIDE 	 AEROBIC GRAM - ve COCCI MODIFIED FROM MASUR et ai, JAMA. MARCH 22129. VOL. 253 NO.12. REFERENCES 9. WRBER B. CHANGING PATTERNS OF INFEC770US .DISEASE. mE AMF..RICAN JOURNAL OF MEDIC/NE, 1988, 84, 569·578. I. COMMUNflY ACQUlRFJJ PNEUMONIA IN ADULTS IN BRITISH HOSPITALS IN 1982 . 1983: A SURVEY OF 10. PALlARES R ET AL: RISK FACTORS ANDAEfIOWGY, MORTALflY, PROGRESSIVE FACTORS RESPONSE TO ANI'IBIOTIC mERAPY IN ADULTSAND OUTCOME. QUARTERLY JOURNAL OF WITH BACTERAEMIC PNEUMONIA CAUSED BYMEDICINE, 1987, 82, 195·220. PENICIlllN RESISTANT PNEUMOCOCCI. NFJM, 1987, 317, 18·22.2. FEKEIY FR, CALDWALL J, GUMP D ET AL, BAClERlA, VIRUSES AND MYCOPLASMA IN AClffE PNEUMONIA 	 IN ADULTS, 1971. 11 . CROFTON 1. DOUGLAS'S RESPIRATORY DISEASES, 4m EDJflON 1989 'PNEUMONIAS' PAGES 285 - 345. 3. SUILJVAN RJ, DOWDLE WR, MARRIE WN, HIERHOUER Je. ADULT PNEUMONIA IN A GENERAL 12. HELMS CM, WINF..R PJ, S1V1M R.4, RENNER ED, HOSPITAL. 	 ARCH. INr. MED. 1972, 129; 935- 942. JOHNSON W. COMPARATIVE FEATURES OF PNEUMOCOCCAL, MYCOPLASMAL AND 4. WHfIE RJ, BLAINEY AD, HARRISON KJ, CLARKE 	 LEGIONNAIRES DISEASE PNEUMONIA: ANNALS OF SKR, CAUSE OF PNEUMONIA PRESENTING TO A MlERNAL MEDICINE 1979, 90, 543-547. DISIRICT GENERAL HOSPITAL. moRAX, 1981,36,566­13. BROOK N, MANUEL RlVERA, J. LlSA LUMAN, WALlACE R: BRANHAMELLA CATARRHALlS AS A 570. WWER RESPIRATORY TRACT PATHOGEN IN AD. HOSPITAL STUDY OF ADULT COMMUNITY 5. MACFARLANE fT, FINCH RG, WARD Al, MACRAE PATIENTS WITH CHRONIC LUNG DISEASE. ACQUIRED PNEUMONIA. LANCET, 1982, 2, 255-258. ARCH. iNTERNAL MEDICINE, 1986, 146, 890·893. 14. WOLLSCHLAGER C, ROOFS, KHAN F, GURARNERI AF. ADULT COMMUNflY ACQUIRED PNEUMONIA 6. MCNABB WR, SHANSON DC, WILLIAMS WM, LAUT JJ, LA BOMBARDI V, AFZAL Q: A CONTROLLED IN CENTRAL WNDON, 1. ROY SOC. MED.)984, 77, COMPARATIVE STUDY OF CIPROFWXACIN VS 550·555. AMPICIUJN IN TREATMENT OF BACTERIAL RESPIRATORY TRACTS INFECTION. AMERICAN 7. MARRlE T GRAYSTON 1. WANG SAN.pEN, KUD 	 JOURNAL OF MEDICINE 82 , 1987, 164-168. CHO-CHOW. PNEUMONIA ASSOCIATED wrm mE 1WAR SIRA1N OF CHLAMYDIA. ANNALS OF lN1ERNAL 15. MASUR H, SHEUIAMER J, PARILW JE. mE MEDICINE, 1987, 106, 507-511 . MANAGEMENT OF PNEUMONIAS IN IMMUNOCOMPROMISED PATIENTS. JAMA, 1985, 8. CHANGING SPELTRUM OF PNEUMONIA - NEWS 	 256. 1769· 1773. MEDIA CREATION OR CUNICAL REALnY, 1983, AMERICAN JOURNAL OF MEDICINE, 74;2. The copyright of this article belongs to the Editorial Board of the Malta Medical Journal. The Malta Medical Journal’s rights in respect of this work are as defined by the Copyright Act (Chapter 415) of the Laws of Malta or as modified by any successive legislation. 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Community-Acquired Pneumonia : what is new in aetiology and treatment

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Community-Acquired Pneumonia : what is new in aetiology and treatment

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