Chapter 7
Evaluation and Initial Treatment of Infectious Complications Among Organ Transplant Recipients
| Site of infection | ||
| Predominant pathogens | Diagnostic investigations | Initial empirical treatment in adult patients |
| GENERAL Fever with no clear focus |
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| Early post-transplant (<1 month): infections at site of transplant (abscess), catheter-related or endovascular infections. Also consider donor-derived infections e.g. West Nile Virus, LCMV Late post-transplant (>1 month): broad differential: viral – CMV, HHV6, EBV(PTLD), adenovirus, respiratory viruses, parvovirus B19; bacterial – TB, MAC, Nocardia, occult abscess at transplant site; fungal – endemic mycoses, Aspergillus, PCP; parasitic – Strongyloides, toxoplasmosis, babesiosis Epidemiologic exposure may guide diagnosis: travel, animal, vector exposure; sexual exposure, etc. Non-infectious causes include rejection, drug fever, neoplasm. |
Multiple blood cultures, urine culture, urinalysis with microscopy, CXR, CMV PCR/antigenemia Image graft site, including vascular anastomosis (ultrasound or CT) If no diagnosis, consider full-body CT scan and EBV PCR Additional tests based on risk factors: nasopharyngeal swab for respiratory viruses PCR, viral PCRs on blood (e.g. parvovirus, adenovirus, HHV6, HIV, WNV); fungal and AFB blood cultures; urine/serum histoplasmosis & blastomycosis antigen; PPD or gamma interferon assay; syphilis screen, toxoplasmosis IgM or PCR (heart transplant); Strongyloides ELISA/stool for multiple O&P If recent transplant, review donor information/contact OPO to see if other recipients also are developing similar presentations |
Early post-transplant: start empiric broad-spectrum antibiotics (e.g. piperacillin-tazobactam 3.375g IV q6h) after all cultures have been taken Late post-transplant: if the patient is stable and not neutropenic, either start empiric antibiotics or consider withholding during initial work-up. If a clinical focus (e.g. pneumonia) is identified, see other sections of this table |
| Septic shock syndrome without clinical focus | ||
| Broad range of infections, primarily bacterial and fungal, may cause acute septic shock Potentially rapidly lethal causes of “septic shock” include bacteremia, vascular thrombosis of an intra-abdominal organ transplant, anastomic leak, cholangitis, necrotizing pancreatitis, toxic megacolon from Clostridium difficile, ischemic/necrotic bowel, bowel perforation including from CMV colitis, necrotizing fasciitis, toxic shock syndrome |
Urgent work-up as per under ‘fever with no clear focus’ to identify abscess or other underlying source Consider empiric discontinuation or replacement of central lines, and culturing catheter tips |
Immediately collect cultures and start broad-spectrum antibiotics: e.g. piperacillin-tazobactam 4.5 g IV q6h or Meropenem 2 g IV q8h + vancomycin 25–30mg IV loading dose × 1 then 15–20mg/kg IV q12h + ciprofloxacin 400 IV q8–12h If severe penicillin allergy, aztreonam 2 g IV q8h + vancomycin 25–30mg IV loading dose × 1 then 15–20mg/kg IV q8–12 + metronidazole 500 mg IV q6h ciprofloxacin 400 IV q8–12h Consider, in place of ciprofloxacin in above regimens, gentamicin 5–7mg/kg IV q24 or colistimethate 2.5mg/kg IV q12 in patients at risk for multi-drug resistant Gram negatives. Consider Echinocandin (e.g. caspofungin 70 mg IV loading dose × 1 then 50 mg IV q24h), especially if recent broad-spectrum antibiotics, TPN, or candida colonization Consider linezolid 600 mg IV q12h or daptomycin 6 mg/kg IV q24h (instead of vancomycin) if there is a recent history of VRE colonization/infection |
| Intravascular catheter-related infections | ||
| Coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp., enteric Gram-negative bacilli, Pseudomonas spp., Candida spp. | If drainage is present, swab entry site for culture Blood cultures × 2 (preferably one via catheter, one via peripheral venipuncture) Culture of catheter tip – aerobic and fungal cultures Note: If the patient has a single blood culture with a Gram-positive cocci or bacilli and is not on vancomycin or similar agent, collect an additional 2–3 blood cultures before initiating vancomycin (on the basis of four blood cultures collected prior to initiation of vancomycin, it may be easier later to distinguish contaminants from pathogens) |
Vancomycin 15 mg/kg IV q12h + Gram-negative bacilli coverage (e.g. cefepime 2 g IV q12h or meropenem 1–2 g IV q8h or piperacillin-tazobactam 3.375 g IV q6h) [If severe penicillin allergy, then ciprofloxacin 400 mg IV q12h or aztreonam 2 g IV q8h for Gram-negative coverage] Consider antibiotic lock therapy to salvage lines in stable patients infected with organisms of low virulence (primarily, coagulase-negative staphylococci). Remove central catheters for most other organisms |
| CENTRAL NERVOUS SYSTEM Central nervous system: acute meningitis/meningoencephalitis |
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| Bacterial: Listeria, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Lyme disease, syphilis, Rickettsia Viral: CMV, HSV, HHV6, VZV, WNV, enterovirus, measles, mumps Other: toxoplasmosis, Strongyloides, microabscesses due to disseminated fungal or bacterial infection Parameningeal infections (e.g. sinusitis, epidural infection) can cause a CSF pleocytosis WNV, LCMV, rabies, Balamuthia, Naegleria have been transmitted from organ donors Non-infectious: drug-induced (e.g. TMP/SMX, ATG), confusion and seizures caused by calcineurin inhibitors (PRES) |
CT/MRI brain Lumbar puncture: opening pressure, CSF cell count and differential, protein, glucose, CSF bacterial, fungal, AFB culture; cryptococcal CSF antigen; HSV PCR, enterovirus PCR, WNV PCR based on epidemiology. Consider other viral PCRs (CMV, HHV6, VZV). Keep additional tube of CSF for future studies. Cryptococcal serum antigen, CMV PCR or antigenemia Consider VDRL/FT-ABS on CSF; Lyme CSF EIA/PCR (with concurrent Lyme serum EIA); WNV serum IgM/IgG EIA and CSF IgM EIA. Consider leptospirosis IgM EIA, Rocky Mountain Spotted Fever IFA/ELISA, ehrlichiosis IFA/ELISA If recent transplant, review donor information/contact OPO to see if other recipients also are developing similar presentations |
If suspect acute bacterial meningitis: ceftriaxone 2 g IV q12h + vancomycin loading dose of 25–30 mg/kg IV × 1, then 15–20 mg/kg IV q8–12h Consider adding ampicillin (for Listeria) 2 g IV q4h (especially if not on TMP/SMX prophylaxis) If CSF has lymphocytic pleocytosis:
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| Meningitis: subacute, chronic | ||
| Bacterial:Mycobacterium tuberculosis, Lyme, syphilis, Brucella, Nocardia Fungal: Cryptococcus, Coccidioides immitis, Histoplasma capsulatum, Candida and other fungi Other: toxoplasmosis, CNS PTLD |
Head CT; consider also brain MRI (for other parameningeal processes, also consider spine MRI) Lumbar puncture: as above per acute meningitis, VDRL, TB PCR and AFB culture (large volume needed), Nocardia culture, cytology – keep additional tube of CSF for future studies PPD or interferon gamma assay, RPR (blood), Cryptococcal serum antigen Consider histoplasmosis antigen in CSF, coccidiomycosis complement fixation (CF) antibody in CSF; urine/serum histoplasmosis and blastomycosis antigen; Consider Lyme CSF EIA/PCR and concurrent Lyme serum EIA. Consider Brucella agglutinating antibody assay, toxoplasmosis IgM/IgG and toxoplasmosis PCR (if previously toxoplasmosis R-, especially after heart transplantation) CT body to identify evidence of systemic disease |
Empiric therapy depends on clinical situation and most likely diagnosis. Might include therapy for Cryptococcus, TB, or other |
| Focal brain disease (abscess or space-occupying lesion) | ||
| Bacterial: septic emboli/local invasion from other sites of infection (broad mix of Gram-positive, anaerobes, Gram-negative bacteria), Nocardia, TB, Actinomyces, Listeria Fungal: Aspergillus, zygomycetes, Cryptococcus and other Other: CNS PTLD, Toxoplasma gondii, neurocysticercosis Non-infectious: other malignancy (primary or metastatic) |
CT/MRI brain If lumbar puncture is safe, consider CSF studies as above plus EBV PCR and galactomannan antigen in CSF Consider CT body, echocardiogram to identify additional lesions (potentially more accessible to biopsy) EBV PCR Consider toxoplasmosis serum IgM/IgG and PCR; serum cryptococcal antigen, serum galactomannan, histoplasmosis urinary antigen, blastomycosis urinary antigen. Consider cysticercosis serology, PPD or interferon gamma assay Aspiration or biopsy under stereotactic CT guidance for aerobic, anaerobic, fungal, AFB, nocardia culture, Aspergillus PCR, TB PCR, and histopathology |
If bacterial brain abscess suspected – meropenem 2 g IV q8h ± vancomycin 15–20mg/kg IV q8–12h Consider voriconazole 6 mg/kg IV q12h × 2 doses, then 4 mg/kg IV q12h or lipid amphotericin product 5–10mg/kg IV q24 |
| Progressive dementia | ||
| JC virus (progressive multifocal leukoencephalopathy); prion diseases; consider other causes of subacute/chronic meningoencephalitis listed above | MRI brain Consider CSF studies above, with addition of JC virus PCR of CSF |
Depends on etiology |
| RESPIRATORY Pharyngitis, tonsillitis |
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| Streptococcus pyogenes (group A), EBV (including PTLD), adenovirus, respiratory viruses | Swab of pharynx for streptococcal antigen (rapid) test or culture NP swab for respiratory virus PCR EBV PCR |
Penicillin VK 250 mg PO QID for streptococcal pharyngitis or Azithromycin 500 mg PO on day 1, then 250 mg daily Oseltamivir 75 mg PO BID if influenza is suspected |
| Sinusitis: community-acquired | ||
| Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, respiratory viruses In CF lung transplant recipients, also Pseudomonas, B. cepacia Fungal: Aspergillus spp., zygomycetes |
Red flags warranting urgent imaging/ENT evaluation: visual or neurologic involvement, prominent headache If there is no improvement after 48 h of decongestants and empirical antibiotic therapy or if patient has any red flags noted above, CT sinuses + ENT consult for aspiration of sinuses/biopsy Consider serum galactomannan assay |
Amoxicillin-clavulanate 875 mg PO BID or Levofloxacin 500 mg PO daily or Azithromycin 500 mg PO on day 1, then 250 mg PO |
| Sinusitis: nosocomial | ||
| Aerobic/facultative, Gram-negative bacilli, Staphylococcus aureus, Aspergillus spp., Zygomycetes | CT sinuses ENT evaluation for endoscopy /sinus aspiration / biopsy |
Piperacillin-tazobactam 4.5 g IV q6h or Cefepime 2 g IV q12h or Meropenem 1–2 g IV q8h |
| Pneumonia (excluding lung transplant)a | ||
| Community-acquired: Streptococcus pneumoniae, Haemophilus influenzae, Legionella spp., Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumonia, respiratory viruses Nosocomial: other Gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp.), Staphylococcus aureus (including MRSA) Opportunistic: fungal – Aspergillus, PCP, Cryptococcus, endemic fungi, zygomycetes, others; viral – CMV, HSV, VZV, adenovirus, others; bacterial – TB, other mycobacteria, Nocardia; parasitic – Strongyloides, toxoplasmosis Non-infectious causes: multiple, including sirolimus pneumonitis, PTLD |
CXR, CT chest Sputum/tracheal aspirate – bacterial, viral, Nocardia, fungal, AFB cultures, PCP stain, respiratory virus PCR (NP swab) CMV PCR (or antigenemia), Legionella urine antigen Consider serum Cryptococcus antigen, serum galactomannan, urine/serum histoplasmosis and blastomycosis antigens Low threshold for BAL: tests as above. Also consider BAL galactomannan, Nocardia culture or PCR assays for other pathogens (e.g. Toxoplasma, Nocardia), cytology If there is pleural effusion, consider thoracocentesis If there are nodular lesions and suspect fungal infection, pursue aggressive diagnostic testing (including BAL and CT-guided tissue biopsy or open-lung biopsy) |
For community-acquired (no recent hospitalizations and post-transplant > 6 months) pneumonia not requiring ICU admission: a respiratory fluoroquinolone (e.g. moxifloxacin 400 mg) PO/IV daily or levofloxacin 750 mg PO/IV daily) or ceftriaxone 2 g IV daily + azithromycin 500 mg PO/ IV daily If possibility of influenza, add oseltamivir 75–150 mg PO BID For more severe or if nosocomial pneumonia: cefepime 2 g IV q8h–q12h or piperacillin-tazobactam 4.5 g IV q6h or meropenem 2 g IV q8h + ciprofloxacin 400 mg IV q8–12h + agent for MRSA (vancomycin 25–30mg IV loading dose × 1 then 15–20mg/kg IV q12h or linezolid 600 IV q12h) If no PCP prophylaxis, (especially within first year post-transplant), consider TMP/SMX (5 mg/kg of TMP component IV q6h) Consider (e.g., for nodular lesions) empiric voriconazole 6 mg/kg IV q12h × 1 day, then 4 mg/kg IV q12h |
| GASTROINTESTINAL/INTRA-ABDOMINAL Oral cavity: stomatitis/mucositis (aphthous, ulcers) |
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| HSV, CMV, Candida Sirolimus-related, idiopathic (aphthous) ulcers |
Viral culture; HSV, DFA, PCR; consider CMV PCR/antigenemia | Valacyclovir 1 g PO BID |
| Oral thrush | ||
| Candida spp. | If atypical appearance, persistent, or relapsing, swab throat for fungal culture and sensitivity testing | Fluconazole 100-200 mg PO daily or Clotrimazole 10 mg troche five times per day or Nystatin suspension (100 000 U/mL) 4–6 mL four times daily, or 1–2 nystatin pastilles (200 000 U each) administered four times daily |
| Esophagitis | ||
| HSV, CMV, Candida spp. | CMV PCR (or antigenemia) of blood Endoscopy and biopsy for viral culture, CMV PCR, histopathology |
Candida: fluconazole 200-400 mg PO daily or caspofungin 50 mg IV q24 If suspect herpesvirus, consider valganciclovir 900 mg PO BID. If severe, consider ganciclovir 5 mg/kg IV q12h |
| Enteritis/colitis | ||
| Bacteria: Salmonella, Campylobacter, Listeria monocytogenes, Clostridium difficile Viral: CMV, EBV (PTLD), enteric viruses (norovirus, adenovirus, rotavirus) Parasitic: Strongyloides stercoralis, Entamoeba histolytica, Giardia lamblia Other: small-bowel bacterial over-growth, especially after liver transplant with Roux-en-Y reconstruction Non-infectious: include drug-induced (MMF, other), and other etiologies |
Stool C&S, O&P; C. difficile toxin (if EIA, collect × 3; if cell culture assay, usually one sample is sufficient) CMV PCR/antigenemia Abdominal X-ray ± CT abdomen Consider Vibrio stool culture if has recently ingested seafood or visited seashore Consider testing of stool for enteric viruses (EIA, DFA, or PCR) Consider colonoscopy with biopsy for viral culture, CMV PCR, and histopathology. Also consider Giardia antigen (EIA) in stool, Cryptosporidium antigen (EIA) in stool, stool for modified AFB (cryptosporidia, isospora, cyclospora), chromotrope stain for microsporidia, serial O&P, Strongyloides ELISA |
Depends on pathogen If recent antibiotics or severe illness, empiric C. difficile treatment (metronidazole or vancomycin, see chapter 30) Consider ciprofloxacin (400 IV q12h or 500–750 PO q12h) Consider empiric CMV treatment (ganciclovir 5 mg/kg IV q12h) while awaiting studies in high-risk persons with severe disease |
| Intra-abdominal: peritoneum and peritoneal space | ||
| Gram-negative bacilli (Enterobacteriaceae, Pseudomonas aeruginosa) Enterococcus spp., Candida spp., Anaerobic bacilli, (Clostridium spp., Bacteroides spp.) | Abdomen/pelvis CT Ultrasound of transplant vasculature (e.g. liver, pancreas, kidney transplants) Diagnostic sampling of peritoneal fluid/abscess. Check fluid bilirubin (liver transplant), creatinine (kidney transplant), or amylase (pancreas transplant) |
Piperacillin-tazobactam 3.375 g IV q6h or meropenem 1–2 g IV q8h If unable to use β-lactams, vancomycin 15mg/kg IV q12 + metronidazole 500 mg IV q6h + (ciprofloxacin 400 mg IV q12h or aztreonam 2 g IV q8h) ± empiric antifungals: fluconazole 400 mg IV/PO daily or echinocandin (e.g. caspofungin 70 mg IV load on day 1, then 50 mg IV daily) If VRE+, add linezolid 600 mg IV q12h or daptomycin 6 mg/kg IV q24h |
| Liver : hepatitis | ||
| Viral: hepatitis A, B, C, E, CMV, HSV, EBV, VZV, HHV6, adenovirus Non-viral: usually as part of disseminated infection, e.g. fungal, mycobacterial Liver transplant: rejection, recurrent underlying disease, graft injury/ischemia Non-infectious: drug-induced |
Image liver: ultrasound, CT, and/or MRI CMV PCR or antigenemia Depending on clinical situation, hepatitis A, B, C serology ± PCR If no diagnosis, consider other viral PCR such as adenovirus, HHV6, VZV, HSV, EBV, hepatitis E serology and PCR Liver biopsy for viral culture, CMV PCR, histopathology; |
Depends on etiology |
| Liver abscess or cholangitis | ||
| Gram-negative bacilli (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter), Enterococcus, Candida spp., Staphylococcus aureus, anaerobic bacilli In liver transplant, biliary stricture can lead to cholangitis, intrahepatic abscess formation. Hepatic artery thrombosis may also lead to recurrent hepatic abscesses |
Image liver: ultrasound, CT, and/or MRI/MRCP. For liver transplant, assess vessels, may need cholangiography Aspiration of liver abscess under CT/ultrasound guidance (prefer to delay antibiotics/antifungals until after aspirate obtained) |
Piperacillin-tazobactam 3.375 g IV q6h or Vancomycin 15mg/kg IV q12h + ciprofloxacin 400 IV q12 + metronidazole 500 mg IV q6h ± Fluconazole 400 IV q24 or caspofungin 50mg IV q24 (guided by culture results) |
| URINARY TRACT INFECTION | ||
| Gram-negative bacilli (Escherichia coli, Klebsiella, Proteus, Enterobacter, Pseudomonas aeruginosa), Enterococcus, coagulase-negative staphylococci, Candida spp. | Image kidneys if suspect upper tract infection or graft pyelonephritis. For recurrent UTI, post-void residual urine assessment, cystoscopy, repeat imaging; consider stent removal Remove urinary catheter as soon as non-essential Note: If Staphylococcus aureus is found in urine culture, the patient should be evaluated for bacteremia |
Outpatient therapy: ciprofloxacin 500 mg PO BID or amoxicillin/clavulanate 875 mg PO BID or cefixime 400 mg PO daily In-patient therapy: piperacillin/tazobactam 3.375 g IV q6h or ciprofloxacin 400 mg IV q12h + vancomycin 15 mg/kg IV q12h For Candida UTI: fluconazole 200–400 mg PO/IV daily. If azole-resistant, ABLC or L-AmB at 3 mg/kg IV daily or caspofungin 70 mg IV × 1 dose, then 50 mg IV daily (poor urine levels but small case series suggest efficacy). Voriconazole has poor urine levels. Amphotericin bladder washes may be used, although efficacy is unclear. |
| SKIN AND SOFT TISSUE Skin and soft tissue infection: Surgical wound infection |
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| Staphylococcus aureus (including MRSA), Enterococcus spp., Gram-negative bacilli (Enterobacteriaceae, Pseudomonas aeruginosa, ) Candida spp. Molds, including Aspergillus and zygomycetes (uncommon) |
Aspiration (needle) or swab of skin exudates for culture Consider imaging to identify deeper abscess |
For mild/superficial cellulitis, amoxicillin-clavulanate 875 mg PO BID or Cephalexin 500 mg PO QID Consider addition of TMP/SMX double-strength PO BID for MRSA If moderately severe, Vancomycin 15 mg/kg IV q12h ± piperacillin-tazobactam 3.375 g IV q6h |
| Skin and soft tissue infection: Cellulitis | ||
| Staphylococcus aureus, Streptococcus pyogenes, occasionally Gram-negative pathogens Causes of persistent cellulitis include Cryptococcus, mycobacteria, molds (e.g. Aspergillus and zygomycetes) |
If progressive despite empiric treatment, consider imaging and skin biopsy (histology and culture, including fungal, nocardia, AFB); consider serum cryptococcal antigen | Cefazolin 1–2 g IV q8h or vancomycin 15 mg/kg IV q12h If diabetic foot ulcer infection, cover for polymicrobial infection (e.g. piperacillin-tazobactam ± vancomycin) |
| Skin and soft tissue infection: papules, nodules | ||
| Disseminated infections: Candida spp., Fusarium spp., Cryptococcus, Aspergillus, histoplasmosis, Gram-negative bacilli (Escherichia coli, Pseudomonas aeruginosa, Aeromonas hydrophilia, Serratia marcescens), Nocardia, atypical mycobacterium, human papillomavirus | Skin biopsy (histopathology; in addition, fresh tissues for aerobic, anaerobic, fungal, Nocardia, and AFB cultures) Consider blood cultures × 2, fungal blood culture × 1 if suspect disseminated infection Consider serum cryptococcal antigen, serum galactomannan assay urine histoplasmosis, blastomycosis antigen |
Depends on etiology |
| Skin and soft tissue infection: ulcers, vesicles, hemorrhagic or crusted lesions | ||
| Herpes simplex, VZV, Staphylococcus aureus, streptococci | Viral culture, HSV/VZV DFA, or PCR of swab from base of unroofed vesicles | HSV: Valacyclovir 1 g PO BID or famciclovir 500 mg PO BID VZV: dermatomal zoster, valacyclovir 1 g PO TID or famciclovir 500 PO TID VZV disseminated disease: acyclovir 10 mg/kg IV q8h |
| Skin and soft tissue infection: skin necrosis | ||
| Aspergillus, Zygomycetes. Embolic phenomenon of endovascular infections of bacterial or fungal etiology, necrotizing fascitis. Pseudomonas, Meningococcus. Other causes of shock, DIC | Blood cultures × 2, including fungal blood culture × 1. Consider serum galactomannan Consider skin biopsy (histology and culture, fungal culture) |
Depends on etiology |
ABLC, amphotericin B lipid complex; AFB, acid-fast bacilli; ATG, anti-thymocyte globulin; BAL, bronchoalveolar lavage; BID, twice daily; CMV, cytomegalovirus; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest X-ray; DFA, direct fluorescent antibody; EBV, Epstein–Barr virus; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; FT-ABS, fluorescent treponemal antibody absorption test; HHV, human herpesvirus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; IgG, immunoglobulin G; IgM, immunoglobulin M; IV, intravenous; L-AmB, liposomal amphotericin B; LCMV, lymphocytic choriomeningitis virus; MAC, Mycobacterium avium complex; MMF, mycophenolate mofetil; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; NP, nasopharyngeal; O&P, ova and parasite; OPO, organ procurement organization; PCP, Pneumocystis jirovecii pneumonia; PO, by mouth; PRES, posterior reversible encephalopathy syndrome; PTLD, post-transplant lymphoproliferative disorder; QID, four times daily; RPR, rapid plasma reagin; SMX, sulfamethoxazole; TB, tuberculosis; TID, three times daily; TMP, trimethoprim; TPN, total parenteral nutrition; UTI, urinary tract infection; VDRL, Venereal Disease Research Laboratory test; VRE, vancomycin-resistant enterococci; VZV, varicella zoster virus; WNV, West Nile virus.
Primary Reference: Glauser MP, Pizzo PA. Management of Infections in Immunocompromised Patients. London: W.B. Saunders Company Ltd, 2000.
aFor pneumonia in lung transplant, see chapter 11.