Infections in Non-HIV Immunocompromised Hosts

Transcription

1 Infections in Non-HIV Immunocompromised Hosts Fredrick M. Abrahamian, D.O., FACEP Associate Professor of Medicine UCLA School of Medicine Director of Education Department of Emergency Medicine Olive View-UCLA Medical Center Sylmar, California Special Populations Discussed Diabetes mellitus Neutropenia Solid-organ transplant recipients Bone marrow transplant recipients Chronic corticosteroid use = Important points = Pitfalls Diabetes & Immune System Alters several aspects of immune system Impairs neutrophil & lymphocyte function Exaggerated with concomitant acidosis Control of hyperglycemia: Normalizes neutrophil function Some evidence reduces incidence of infection Walrand S, et al. J Leukoc Biol. 2004;766: [Insulin & neurophil function] Van den Berghe G, et al. N Engl J Med. 2001;345: [SICU & insulin therapy] 1

2 Diabetes Mellitus & Risk of Infection DM as risk factor for community-acquired infections 7417 DM vs. 18,911 control patients with HTN Increased risk for LRTIs, SSTIs, UTIs Infections strongly associated with DM: Emphysematous pyelonephritis Malignant otitis externa Mucormycosis (zygomycosis) Emphysematous cholecystitis Muller LMAJ, et al. Clin Infect Dis. 2005;41: [Risk of infection & DM] Diabetes & Microorganisms Group B Streptococcus 37% in % in 2007 Bacteremia without focus, SSTIs, & pneumonia Klebsiella: Bacteremia, liver abscess Tuberculosis 4 x more frequent than in general population Aggressive, lower lobes, with pleural effusion Candida species Oropharynx, perineum, cutaneous (intertriginous) Skoff TH, et al. Clin Infect Dis. 2009;49: [Group B strep & DM in adults] Broxmeyer L. Med Hypotheses. 2005;65: [DM & TB relationship] 2

3 Question to Audience Antimicrobial therapy against Pseudomonas & MRSA is essential in all types of diabetic foot infections. True False Diabetic Foot Infections Pseudomonas & MRSA not common culprits Specimen collection for culture: Best from debrided base by curettage or biopsy Superficial wound swab not preferred Consider osteomyelitis when: Ulcer does not heal after 6 weeks of therapy Bone visible or palpable with a probe Treat concomitant fungal infections Citron DM, et al. J Clin Micrbiol. 2007;45: [DFI microbiology] Lipsky BA, et al. Clin Infect Dis. 2004;39: [IDSA guidelines on DFI] Grayson ML, et al. JAMA. 1995;273: [Probing bone & osteomyelitis] Question to Audience Asymptomatic bacteriuria in a diabetic patient always requires antimicrobial therapy. True False 3

4 Diabetes Mellitus & UTI Higher incidence of asymptomatic bacteriuria in Pyuria commonly present Dx based on culture Treatment not recommended 7 day Tx recommended for symptomatic cystitis Poor response / persistent fever think complications Abscess, necrosis, & emphysematous infections 48 hrs Tx + no clinical improvement = CT scan Nicolle LE, et al. Clin Infect Dis. 2005;40: [IDSA guidelines on ASB] Hoepelman AI, et al. Int J Antimicrob Agents. 2003; 22:S35-S43. [Cystitis & diabetes] Emphysematous Pyelonephritis Life-threatening, suppurative, necrotizing infection E. coli most common cause CT scan imaging modality of choice Differentiate emphysematous pyelonephritis: Emphysematous pyelitis Emphysematous cystitis Broad-spectrum antibiotics (cover Pseudomonas) Immediate surgical consultation Huang JJ, et al. Arch Intern Med. 2000;160: [Emphysematous pyelo; prognosis] Abdul-Halim H, et al. Urol Int. 2005;75: [Emphysematous pyelo; management] 4

5 Malignant Otitis Externa Habif TP. Clinical Dermatology Malignant Otitis Externa Involves external auditory canal & temporal bone Pseudomonas most common culprit Fever commonly absent Confused with severe perichondritis or otitis externa Workup includes CT scan / MRI of temporal bone Initiate antipseudomonal therapy Consult ENT Cultures to determine susceptibility Tissue biopsy R/O epidermal carcinoma Debridement usually required Berenholz L, et al. Laryngoscope. 2002;112: [Pseudomonas resistance to Cipro] Rhinocerebral Mucormycosis Infection involves sinuses & surrounding structures Clues to Dx: Ulcers, black eschars on palate, nasal mucosa Dx: Biopsy & culture of necrotic tissue Workup includes CT / MRI of head & neck Initiate high-dose IV amphotericin B Major concern nephrotoxicity Newer lipid formulations with less toxicity Emergent surgical consultation Perfect JR. Clin Infect Dis. 2005;40:S401-S408. [Amphotericin lipid complex] 5

6 Emphysematous Cholecystitis Clinically similar to acute cholecystitis More common in males Gangrene & perforation more frequent High rate of mortality Gallstones present (50%) Dx: Abdominal CT scan Microbiology: E. coli, C. perfringens, B. fragilis Initiate broad-spectrum antibiotic therapy Emergent surgical consultation Garcia-Sancho Tellez L, et al. Hepatogastroenterology. 1999;46: [Case reports] Neutropenia & Fever Neutropenia: Neutrophils < 500 cells/mm 3 or < 1000 with a predicted decrease to < 500 Fever: Single oral temp 38.3 C (101 F) Temp 38.0 C (100.4 F) for 1 hour Risk or severity of infection increases with: Decreasing neutrophil count Duration of neutropenia > 7-10 days Hughes WT, et al. Clin Infect Dis. 2002;34: [IDSA guidelines neutropenic fever] Clinical Presentation Fever may be only feature of infection Signs & symptoms of infection may be minimal Pain despite absence of signs suspect occult infection Special attention to: Oral cavity, perineum, toes, bone marrow aspiration site & vascular catheters Look for splenectomy scar Higher risk of infection with S. pneumoniae, H. influenzae, & N. meningitidis 6

7 Bacterial Microbiology Majority: Gram-positive organisms Staphylococcus & streptococcus species Enterococcus faecalis / faecium Corynebacterium species (PICC lines) Gram-negative organisms Escherichia coli, Klebsiella species Pseudomonas aeruginosa Anaerobes uncommon, unless: Oral mucositis, perirectal, intra-abdominal source Initial Evaluation Initial workup must include blood cultures (x 2) One set from device lumen (if present) Gram stain & culture of exudate at catheter entry site (if present) Initiate empiric antibiotic therapy: All febrile neutropenic patients Afebrile neutropenic patients with signs & symptoms of infection Hughes WT, et al. Clin Infect Dis. 2002;34: [IDSA guidelines neutropenic fever] Neutropenic Fever: Decision-Making Process High risk (Consider age 16 high risk) Low risk Admit IV antibiotics No Outpatient therapy Single vs. dual therapy? Yes Decide if need to add Vancomycin & Metronidazole Always involve Heme/Onc Cipro plus amox-clav Hughes WT, et al. Clin Infect Dis. 2002;34: [IDSA guidelines neutropenic fever] 7

8 Choices of IV Antibiotics Monotherapy (uncomplicated) Dual Therapy (complicated i.e., ICU admission) Cefepime Ceftazidime Imipenem Meropenem Piperacillin-tazobactam Ticarcillin-clavulanate Cefepime or Ceftazidime Imipenem or Meropenem plus Gentamicin, Tobramycin, or Amikacin Hughes WT, et al. Clin Infect Dis. 2002;34: [IDSA guidelines neutropenic fever] Bow EJ, et al. Clin Infect Dis. 2006;43: [Pip/tazo vs. cefepime neutropenic fever] Question to Audience Vancomycin is essential antimicrobial therapy for all neutropenic patients presenting with fever. True False Additional Antibiotics Add vancomycin if: Septic shock Catheter-related infection (bacteremia, cellulitis) Known history of MRSA On prophylactic therapy with quinolones Add metronidazole if using cefepime/ceftazidime: Oral mucositis Perirectal infection Intra-abdominal infection 8

9 Multinational Association for Supportive Care in Cancer Risk Index (MASCC ) To identify low-risk for complications in febrile neutropenic cancer patients Age > 16 years Derivation n=756 Validation n=383 Risk-index score 21 PPV 91% ; NPV 36% Sensitivity 71% Specificity 68% Misclassification rate 30% Characteristic No or mild symptoms No hypotension No COPD Solid tumor or no prior fungal infection No dehydration Moderate symptoms Outpatient status Age < 60 years Wt Klastersky J, et al. J Clin Oncol. 2000;18: [Identifying low-risk of complications] Other Factors Favoring Low-Risk Absolute neutrophil count 100 cells/mm 3 Neutropenia < 7 days Peak temp < 39ºC & RR 24 breaths/min Normal chest X-ray No IV catheter-site infection Disposition Decision always made with Heme-Onc Patient agreeable to plan Obtain consent Ability to care for self /or presence of a caregiver Ability to access medical care IV Catheter-Related Infections Most common cause of catheter-related infection: Coag-negative staph (often methicillin-resistant) Vancomycin first line of therapy Removal indicated if : Signs of infection (pain, erythema, purulence, induration) Septic shock with no other source of infection In general, not emergent to remove lines in ED Always involve Hem-Onc Mermel LA, et al. Clin Infect Dis. 2009;49:1-45. [IDSA guidelines on catheter infections] 9

10 Infections in Solid-Organ Transplant Recipients Difficult to differentiate infection from rejection Broad spectrum of potential pathogens Dx often requires invasive diagnostic procedures Predictive temporal pattern of infections: < 1 month: Nosocomial & post-op infections 1-6 months: Opportunistic infections > 6 months: Community-acquired infections Fishman JA. N Engl J Med. 2007;357: [Infection in organ transplant recipients] Infections in Bone Marrow Transplant Recipients Predictive temporal pattern of infections 0-30 days Profound neutropenia Primarily involves skin, liver, & GI tract Bacterial infections common Alters neutrophil days function Acute graft vs. host dz. Further adds to immunosuppression CMV infection Increases risk of > 100 days infections S. pneumoniae, H. influenzae Infections & Corticosteroid Use Interferes with many aspects of immune system Chronic use predisposes to a variety of infections Equivalent 15 mg /day prednisone 1 month Risk of infectious complications multifactorial Underlying medical condition Route of administration Dose: Risk if > 10 mg/day or cumulative dose of > 700 mg of prednisone Durations of therapy: Risk if given > 21 days Stuck AE, et al. Rev Infect Dis. 1989;11: [Risk of infections & dose of steroids] 10

11 Infections & Corticosteroid Use Broad spectrum of potential pathogens Most infections due to pyogenic bacteria S. aureus & streptococci Enterobacteriaceae Tuberculosis Often miliary or disseminated Chronic use suppresses tuberculin reactivity Induration 5 mm is considered positive Consider fever etiology infectious until proven otherwise CDC. MMWR. 2000;49(No. RR-6):1-51. [Tuberculin skin testing & steroid use] Rovin BH, et al. Kidney Int. 2005;68: [Fever in patients with SLE] Take Home Points Diabetic foot infections: Think osteo if persistent ulcer after 6 weeks of effective therapy Pyelonephritis & DM: CT if 48 hrs of Tx & no clinical improvement Malignant otitis externa: Needs culture & biopsy Take Home Points Neutropenic febrile patients: Initiate antipseudomonal therapy in all patients Solid-organ transplant patients: Difficult to differentiate infection from rejection Chronic steroid use & tuberculin reactivity: Induration 5 mm is considered positive 11