Management of infective complications in patients with advanced hematologic malignancies in home care

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1 Leukemi (1997) 11, Stockton Press All rights reserved /97 $12.00 Mngement of infective complictions in ptients with dvnced hemtologic mlignncies in home cre C Girmeni, ML Moleti, C Crtoni, M Cedrone, C De Gregoris, V De Snctis, M Giovnnini, R Ltglit, P Niscol, C Romni, MB Rondinelli, S Tosti nd F Mndelli Deprtment of Cellulr Biotechnology nd Hemtology, University L Spienz, Rome, Itly A home cre service hs been implemented t our center with A home cre service (HCS) hs been recently implemented the im of offering domiciliry ssistnce to ptients with hem- t our Hemtology Center in Rome with the im of offering tologic mlignncies in dvnced phse. We report our experithe continuity of pllitive nd/or supportive cre t home to ence concerning the home mngement of these ptients in the setting of infective complictions. Of 151 ptients in home ptients with hemtologic mlignncies in dvnced phse cre, 70 (46%) developed totl of 109 febrile episodes, performnce sttus nd neutrophil count significntly ffecting the cerning incidence, predisposing cuses, prognostic fctors without hope of cure. This pper reports our experience con- incidence of infections. Fever ws of unknown origin in 51% of nd fesibility of home mngement of infective complicses nd microbiologiclly nd cliniclly documented infec- ctions in ptients with dvnced hemtologic mlignncies tions ccounted for 26 nd 23% of the cses, respectively. Orl in home cre. ciprofloxcin in ptients not neutropenic nd intrvenous ceftrixone plus mikcin in neutropenic ptients ws shown to be effective nd suitble for empiric home ntibcteril tretment; in fct, 65% of febrile episodes responded to the initil Ptients nd methods ntibcteril therpy with further 16% fter modifiction. Overll, 19.3% of the infective episodes were ftl, the prog- From September 1993 to Februry 1996, 151 ptients with nosis ppering to be similr to tht usully observed in the hemtologic mlignncies in dvnced phse ccepted to sme ctegory of ptients in n inptient setting. Our experireceive domiciliry ssistnce tht ws given until deth or, ence ppers to show tht home cre progrm could be the option of choice for ptients with dvnced cncer even in the less frequently, until improvement of the generl conditions. setting of infective complictions. It could improve the qulity Ptients with hemtologic mlignncies in dvnced phse of life of ptients nd of their fmilies, nd it could sve these were considered to be those in poor generl condition with subjects the risk of developing infections by resistnt disese in relpse nd/or resistnt, ineligible for ny tretment nosocomil isoltes. or with underlying situtions contrindicting n intensive Keywords: home cre; hemtologic mlignncies; infections chemotherpy (ie dvnced ge, other illnesses). Our HCS ws composed of severl physicins nd nurses, nd of welfre officer from our hospitl. An infectious dis- Introduction ese specilist, hert specilist, neurologist nd surgeon were vilble. Medicl exmintions, lbortory nlyses, One of the most distressing moments during the close mnintrvenous infusions, prenterl nutrition nd psychosocil gement of cncer ptients is when only pllitive or supportsupport were performed dily. In every medicl nd nursing ive therpy is indicted nd, ultimtely, ll hopes of cure re ccess, the evlution of generl clinicl conditions ws lost. The poor clinicl condition of these subjects nd the recorded ccording to Krnofsky s Scle of Performnce Sttus occurrence of severe complictions require close medicl sur- (KPS). 9 Hemtologicl nlyses, chemistry nd microbiologiveillnce with recurrent nd prolonged hospitliztions. The cl nlyses were sent to the lbortories of our Hospitl. No desire of cncer ptients to spend s much time s possible ntimicrobil prophylxis ws dministered, even in neutrot home during the pllitive or terminl phse of their illness penic ptients. A doctor on continuous duty ws vilble nd the high costs of hospitliztion, re the min motives 24 h dily, ll yer round. In the event of fever or other clinibehind the development of strtegies tht move trditionlly cl signs of infection, the doctor on duty performed clinicl inptient problems or therpies to the outptient setting. 1 5 evlution nd lbortory exmintions t the ptient s home Thus, different clinicl pproch could be justified in prior to dministering ntimicrobil therpy: complete ptients in dvnced phse of their mlignncy nd the instiphysicl exmintion nd cultures from blood nd, s clinitution of domiciliry ssistnce could be sfe nd cost-svclly indicted, from urine, stools nd ny other presumed site ing lterntive. Infective complictions ply mjor role in of infection. Blood cultures were repeted dily in the fce of the morbidity nd mortlity in ptients with progressive cnpersistent fever or if the ptient ws bcteremic, until cultures cer, prticulrly those with hemtologic mlignncies. The were negtive. Febrile episodes were clssified s microbiostndrd recommendtion is tht these ptients remin hospilogiclly documented infections with or without bcteremi, tlized until the compliction hs resolved. 6 8 Thus, home cliniclly documented infections on the bse of physicl mngement of serious infections in ptients with dvnced exmintion nd fever of unknown origin. Febrile episodes hemtologic mlignncies could represent n importnt medicliniclly considered noninfectious (such s neoplstic, cl nd ethicl problem, unless continuous ssistnce by chemotherpy-induced nd trnsfusion-induced fever) were skilled physicins nd nurses is vilble. not included in the study. In severely neutropenic ptients (PMN 500/mm 3 ) single dily dose empiric intrvenous therpy with ceftrixone (2 g) plus mikcin (20 mg/kg) ws Correspondence: C Girmeni, Deprtment of Cellulr Biotechnology nd Hemtology, University L Spienz, Vi Benevento 6, dministered (the first dose by the doctor nd subsequently by Rome, Itly; Fx nurses). In ptients not neutropenic orl therpy with cipro- Received 8 April 1997; ccepted 14 August 1997 floxcin ( mg twice dy) ws usully given; ptients

2 1808 Infections in ptients with hemtologic mlignncies in home cre with upper respirtory trct infection were treted with moxicillin (1 g/three times dy). Empiric ntibiotic therpy ws djusted on the bse of clinicl signs, the results of culture nd sensitivity tests, nd therpeutic response. Antibiotic tretment ws continued until 4 consecutive dys without fever or until microbiologicl nd/or clinicl evidence of infection disppered. Antibiotic tretment ws regrded s success if fever nd clinicl signs of infection (whenever present) resolved nd if the infecting microorgnisms (whenever isolted) were erdicted with the empiric or modified ntibiotic therpy. the study period, 70 (46%) developed totl of 109 febrile episodes of proven or presumed infective origin. Eighty-one (54%) ptients did not develop ny infective episode. One episode of infection occurred in 48 (69%) ptients, while two, three nd more thn three episodes occurred in 13 (19%), six (9%) nd three (4.3%) ptients, respectively. Only one ptient refused home cre nd ws hospitlized in the setting of n infective compliction. Fctors influencing the occurrence of infection Clinicl chrcteristics nd fctors influencing the occurrence Results of infection by compring ptients who developed with those tht did not develop n infective compliction re described Chrcteristics of ptients in Tble 2. The two groups of ptients were similr in sex, ge nd underlying disese. Previous intensive chemotherpy The men ge of the 151 ptients ws 58 yers (rnge, 4 94). nd hospitliztion within 15 dys before strt of home cre There were 80 (53%) mles nd 71 (47%) femles. The dur- did not influence the incidence of infections. The men durtion tion of home cre rnged from 1 to 335 dys, with n verge of home cre ws 52 nd 24 dys, in infected nd nonintion of 37 dys. Eleven ptients (7.3%) whose generl con- fected ptients, respectively (P = ). The incidence of dition improved were newly dmitted to mbultory cre, nd infections ws inversely correlted with the severity of generl 19 ptients (12.6%) were hospitlized due to worsening gen- conditions. Fifty-five percent of ptients with KPS 40 t the erl condition nd/or refusl of home cre. The remining 121 onset of home cre developed n infective compliction s (80%) ptients continued to be mnged t home until deth. compred with rte of 39% in ptients with KPS 40 One hundred (66%) ptients survived more thn 2 weeks from (P = 0.03). However, the men durtion of home cre ws the beginning of domiciliry ssistnce. Underlying diseses, 47.4 dys in ptients with KPS 40 nd 27.8 dys in ptients previous therpy, the generl condition t the onset of home with KPS 40, with n verge of nd infective cre, the number of neutropenic ptients with durtion nd episodes per dy, respectively. In 63 ptients the peripherl severity of neutropeni re presented in Tble 1. Acute leukemi PMN count ws persistently or occsionlly less thn nd lymphom were the most common underlying dis- 500 mm 3 ; the infection rte in these ptients ws 63%, s eses ccounting for 64% of dignoses. Fifty-four percent of compred with rte of 34% in the ptients whose peripherl ptients hd previously treted hemtologic disese in PMN count ws persistently 500 (P = ). relpse or unresponsive to cytotoxic chemotherpy nd 46% of ptients hd not been treted with intensive chemotherpy due to dvnced ge nd/or poor generl condition. Site of infection nd microbil isoltes Sites of infection, microbil isoltes nd ssocited mortlity Incidence of infection re described in Tbles 3 nd 4. Febrile episode ws of Of the 151 ptients with hemtologic mlignncies in unknown origin in 56 cses (51%) nd in 25 episodes (23%) the infection ws only cliniclly documented. Microbiologidvnced phse who received domiciliry ssistnce during clly documented infections occurred in 28 (26%) episodes, of which 17 were septicemis (14 without nd three with documented orgn involvement) (Tble 4). Nine episodes of Tble 1 Chrcteristics of 151 ptients with dvnced hemtolpulmonry infection occurred, this being the most frequent ogic mlignncies in home cre site of infection, nd six ptients died. Septic shock occurred Chrcteristic No. % in 11 ptients nd in eight cses (72%) it ws ftl. Overll, 21 (19.3%) infective episodes were ftl. An infective compliction ws the cuse or contributed to deth in 14% of ll Underlying disese Acute myeloid leukemi ptients in home cre. Acute lymphoid leukemi 14 9 P. eruginos ws isolted most frequently (nine cses), fol- Chronic myeloid leukemi lowed in order by S. ureus (five cses) nd E. coli (three Other myeloprolifertive disorders 9 6 cses). Susceptibility to ciprofloxcin, ceftrixone nd mik- Chronic lymphoid leukemi 10 7 cin, respectively, were 89, 56 nd 89% for P. eruginos; 71, Lymphom Other mlignncies nd 86% for stphylococci (43% of these strins were sus- Previous intensive chemotherpy ceptible to oxcillin nd 100% to vncomycin nd Yes teicoplnin); nd 71, 86 nd 86% for the other erobil No Generl conditions t the onset of home cre bcteril isoltes. KPS KPS Neutropenic ptients (PMN 500 mm 3 ) Tretment of infections Men dys of neutropeni/men dys of home cre PMN /37 38 Forty-five febrile episodes in ptients not severely neutropenic PMN 100 4/37 11 were empiriclly treted with orl ciprofloxcin. Orl moxicillin ws dministered in five ptients with cute purulent ton-

3 Tble 2 Infections in ptients with hemtologic mlignncies in home cre Fctors influencing the occurrence of infective complictions in ptients with dvnced hemtologic mlignncies in home cre 1809 Fctors Totl No. of Infected Noninfected P ptients Sex, mle/femle, No. (%) 80/71 37/33 (46/46) 43/38 (54/54) NS Men ge NS Underlying disese, No. (%) NS Acute leukemi (44) 33 (56) Chronic myeloid leukemi (54) 11 (46) Lymphom (42) 21 (58) Generl conditions t the onset of home cre, No. (%) 0.03 KPS (55) 32 (45) KPS (39) 49 (61) Men dys of home cre Grnulocyte count, No. (%) (34) 58 (66) (63) 23 (37) Previous intensive chemotherpy, No. (%) Yes (44) 46 (56) No (49) 35 (51) NS Hospitliztion within 15 dys before home cre, No. (%) Yes (41) 37 (59) No (50) 44 (50) NS Fisher exct test nd Student s t-test s pproprite. Tble 3 Sites of infection nd mortlity in 109 febrile episodes in ptients with dvnced hemtologic mlignncies in home cre Site of infection No. of episodes (%) No. of deths (%) Unknown 56 (51) 8 (14) Systemic, septicemi 14 (12.8) 3 (21.4) Meningitis 1 (0.9) 1 (100) Skin nd soft tissue Cellulitis 9 (8.3) 1 (11) Herpes zoster/simplex disseminted 3 (0.3) Respirtory Acute purulent tonsillitis 5 (4.6) Sinusitis 1 (0.9) Pneumoni 9 (8.3) 6 (66.6) Gstrointestinl Esophgitis 1 (0.9) Perirectl bscess 7 (6.4) 2 (28.6) Urinry trct infection 2 (1.8) Osteomyelitis 1 (0.9) Totl 109 (100) 21 (19.3) Without signs of orgn involvement. sillitis. Seven ptients not neutropenic, with low complince Prognostic fctors for orl tretment received intrvenous ceftrixone. The combintion of ceftrixone plus mikcin ws dministered in 46 As previously observed, 11 ptients were newly dmitted to febrile episodes in severely neutropenic ptients. Three mbultory cre, 19 were hospitlized nd 121 ptients died ptients with severe herpetic infections received orl cyclo- t home. Overll, n infective compliction ws the cuse of vir. Two ptients with Cndid prpsilosis fungemi nd deth in 21 (17.4%) cses, nd bout 80% of deths were Cndid lbicns esophgitis received orl nd intrvenous directly relted to noninfective complictions of the underlying fluconzole, respectively. One ptient with rpidly ftl septic mlignncy. In prticulr, 41 ptients (eight with infective shock did not receive ny ntibiotic therpy. Fifty-six (89%) compliction) died t home within 2 weeks from the beginning of 63 febrile episodes in ptients not neutropenic responded of domiciliry ssistnce. to initil empiric ntibiotic therpy (45 cses) or fter modifi- Fctors influencing the outcome of infection re evluted ction (11 cses). Out of 46 episodes of neutropenic fever, 32 in Tble 5. Sex, ge nd underlying disese did not influence (70%) responded to initil empiric therpy (26 cses) or fter significntly the prognosis of infective complictions. An modifiction (six cses). incresed mortlity rte ws correlted with severity of gen-

4 1810 Tble 4 Infections in ptients with hemtologic mlignncies in home cre Microbil isoltes, site of infection nd outcome in ptients with dvnced hemtologic mlignncies in home cre Isoltes Septicemi Cutneous cellulitis Other sites Totl No. of (site) isoltes Grm-negtive P. eruginos 5 (2) 4 (1) 9 (3) E. coli 2 1 (urinry trct) 3 Proteus mirbilis 1 b (urinry trct) 1 Acinetobctes sp. 1 1 Grm-positive S. ureus 3 (1) 1 1 (sinusitis) 5 (1) S. epidermidis Str. pneumonie 1 b (meningitis) (1) 1 (1) E. feclis 1 1 Nocrdi spp. 1 1 Anerobes 1 1 b (perirectl bscess) (1) 2 (1) Cndid lbicns 1 (esophgitis) 1 Cndid prpsilosis 1 1 Totl 14 (3) 8 (1) 6 (2) 28 (6) Without signs of orgn involvement. b With septicemi. The number of deths is shown in prentheses. Tble 5 Prognostic fctors of febrile episodes in ptients with dvnced hemtologic mlignncies in home cre Fctors Totl febrile episodes Ptients died Ptients survived P Sex M/F 52/57 7/14 45/43 NS Men ge NS Underlying disese NS Acute leukemi Lymphom Chronic myeloid leukemi Generl condition t the onset of infection KPS KPS Neutrophyl count PMN 500/mm PMN 500/mm Fisher exct test nd Student s t-test s pproprite. erl conditions nd neutropeni. Thirty-one percent of ntibiotic therpy, the overll number of medicl nd nursing ptients with KPS 40 t the time of the infective compliction ccesses ws 420 nd 685, respectively (0.44 nd 0.72 per died s compred with rte of 4% in ptients with dy, respectively). KPS 40 (P = ). An incresed mortlity ws observed in severely neutropenic ptients (30%) s compred to ptients with neutrophil count 500/mm 3 (11%) Discussion (P = ). Incresing ttention to the improvement of the qulity of life nd to the cost sving in the mngement of cncer ptients Medicl nd nursing home cre hs led to the development of strtegies tht move trditionlly inptient problems to the outptient setting. The cumultive number of home cre dys in the 151 ptients Severl lrge studies seem to suggest tht outptient mnws 5594 (37 men dys, 20 medin dys). In 3389 dys gement of the infections in low-risk ctegories of cncer (61%) the ptient ws in serious generl condition ptients whose medicl condition is likely to remin stble is (KPS 40) requiring close medicl surveillnce. The cumult- sfe nd effective, is well received by ptients, nd my prove ive number of medicl nd nursing ccesses ws 2230 nd to be cost-sving. 6,10 16 In contrst, the high overll medicl 2403 in the overll dys of home cre (0.40 nd 0.43 per dy, risk of other ctegories of ptients such s those with severe respectively). In the 2205 dys in which ptient KPS ws 40, neutropeni or with uncontrolled mlignncy, pprently jus- there were 0.17 medicl nd 0.19 nursing ccesses per dy. tifies in-hospitl tretment until the infective compliction hs In the 3389 dys in which ptient KPS ws 40, medicl nd resolved, since close medicl surveillnce nd the redy vilnursing ccesses were 0.55 nd 0.59 per dy, respectively. bility of emergency cre could benefit rpidly deteriorting With regrd to the 950 cumultive dys of home cre during ptients. However, recurrent hospitliztions, even limited to infective complictions, clculted s the number of dys of the close mngement of complictions, could negtively

5 Infections in ptients with hemtologic mlignncies in home cre ffect the qulity of life of these subjects nd of their fmilies, tgeous, 2 4,17 the overll costs borne by both our HCS nd with high costs nd, in severl cses, without significnt ptients re not vilble; thus, the economic impct of the clinicl dvntge. mngement of ptients with dvnced hemtologic mlignncies Our experience ppers to show tht home cre progrm, t home cnnot be ssessed by our study. which llows the continuity of pllitive nd/or supportive In conclusion, it is generl feeling tht home cre services cre t home could be the option of choice for cncer ptients hve n importnt role in humnising the cre of ptients with without hope of cure, even in the setting of serious medicl dvnced cncer, lso considering tht most cncer ptients complictions such s, first of ll, infections. wish to die t home, 1 with the sme trend being reported in In our study the infection rte occurring t home in the set- n Itlin popultion. 18 Our experience ppers to show tht ting of dvnced hemtologic mlignncies ws 46%; ltogether, n dvnced nd integrted home cre progrm with continu- 109 episodes of infection were observed, with n ver- ous ssistnce by skilled physicins nd nurses, with doctor ge of 0.72 episodes per ptient, nd the men durtion of vilble 24 h dily nd with complete lbortory support, the infective episodes, considered s the number of dys of could be sfe nd effective lterntive to hospitliztion for ntibiotic therpy, ccounted for 17% of the overll home the mngement of infections in ptients with dvnced hem- cre period. Only one ptient decided to be hospitlized in tologic mlignncies. Nevertheless, we re wre of the the setting of infective compliction. A significntly incresed difficulties in the vilbility of similr home cre system incidence of infections ws ssocited with neutropeni nd elsewhere. prlleled the durtion of home cre. However, the men Severl spects should be underlined: (1) Domiciliry ssist- incidence of infective complictions per dy of home cre in nce lso in the setting of severe complictions could improve ptients with different generl conditions ws comprble. the qulity of life of ptients nd of their fmilies, even if some Septicemi, pneumoni, cellulitis nd perirectl bscess ptients consider hospitliztion more comfortble nd more were the most frequent infections. Pneumoni ws ssocited secure. (2) Our study seems to show tht outptient mnge- with high mortlity rte, but most cses occurred s ter- ment sves these subjects with dvnced cncer the risk of minl event in criticlly ill ptients. Since chest X-ry ws only developing infections due to highly pthogenic nd ntimicro- rrely obtined t home, the incidence of pulmonry infec- bil resistnt nosocomil isoltes. In view of the bove, home tions ws probbly underestimted. P. eruginos nd mngement of other ctegories of cncer ptients, such s S. ureus were the most common cuses of bcteremi those receiving intensive chemotherpy, could be hypothesized. ccounting for 50% of ll microbil isoltes. Only minority Recent dvnces in ntimicrobil therpy, including the of P. eruginos nd S. ureus infections were ftl (three of vilbility of brod-spectrum betlctm ntibiotics with nine, nd one of five, respectively). Therpy with orl ciprofloxcin long hlf-lives nd the development of orl ntipseudomonl nd once dy intrvenous ceftrixone plus mik- gents, represent n importnt tool to llow n efficcious nd cin in not neutropenic nd neutropenic ptients, respectively, mngeble home ntimicrobil therpy. 13,15,19 21 (3) A pro- ws shown to be effective nd suitble for empiric home nti- spective study to estimte the direct nd indirect economic bcteril tretment; in fct, 65% of febrile episodes responded costs of such home cre progrm is needed, especilly given to the initil ntibcteril therpy with further 16% fter the current trend towrds outptient cncer cre. modifiction. Despite severe nd persistent immunocompromise of our ptients nd the severity of the infections they suffered, less Acknowledgements thn 20% of ll infective episodes were ftl nd infectionrelted mortlity ws 17.4%. Importntly, most ftl infections We wish to thnk the welfre officer AM Pietrngeli nd the occurred while the ptient ws in very terminl phse of nurses F Piterà Quttromni, G Bugtti, M Cmeli, M Gin- underlying mlignncy nd generl conditions were progresstheir poletti, P Mggiore, G Piccolo, P Scocci nd L Spll, for ively worsening, wheres only 4% of infective episodes in vluble contribution in the ssistnce of our ptients. ptients with KPS 40 were ftl. This work ws supported by ROMAIL (Associzione Itlin The microbiologiclly nd cliniclly documented infection contro le Leucemie, sezione di Rom) nd in prt by grnts rte nd the etiology of infections we observed in ptients t from Schering-Plough Interntionl. home ppered to be similr to those usully observed in the sme ctegory of ptients in n inptient setting. 17 Importntly, most bcteril isoltes, lso those frequently References developing multidrug resistnce, showed in vitro ntimicro- 1 Townsend J, Frnk A, Fermont D et l. 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Cncer 1993; 71: ptients were in poor generl condition (KPS 40) due to dvnced mlignncy or severe complictions, especilly 6 Tlcott JA, Siegel RD, Finberg R, Goldmn L. Risk ssessment in infections. In this setting, home cre with reltively low cncer ptients with fever nd neutropeni: prospective, two- center vlidtion of prediction rule. J Clin Oncol 1992; 10: number of medicl nd nursing ccesses (0.55 nd 0.59 per dy, respectively) ws ble to void probble hospitliztion, 7 Pizzo PA, Robichud KJ, Gill FA, Witebsky FG. Empiric ntibiotic ccording to KPS definitions. 9 Although outptient cre for nd ntifungl therpy for cncer ptients with prolonged fever ptients with cncer is considered to be economiclly dvn- nd grnulocytopeni. Am J Med 1982; 72:

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