Therapy and Management of Pneumocystis jirovecii Infection
Abstract
:1. Introduction
2. Diagnosis
3. Primary Prophylaxis
3.1. HIV-Positive Population
3.2. Solid Organ Transplant Recipients
3.3. Haematology Patients
3.4. Other Populations
4. Therapy
4.1. HIV-Positive Population
4.2. Solid Organ Transplant Recipients
4.3. Haematology Patients
5. Secondary Prophylaxis
6. Side-Effects and Interactions
7. Resistance
8. Outbreaks
9. Paediatrics
10. Concluding Remarks
Author Contributions
Conflicts of Interest
References
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Underlying Disease | Number of Cases/ Medical History | Treatment | Outcome | Reference |
---|---|---|---|---|
Severe alcoholic hepatitis | 2 | Not available | Both died | [10] |
Giant cell arteritis | 7 F = 5 M = 2 | All on prednisone at diagnosis of PcP No PcP prophylaxis All received trimethoprim/sulfamethoxazole for PcP | 5 recovered 2 died | [8] |
Crohn’s disease. | 1 M, 19 y Post-marketing surveillance through June 2001, ntified 10 cases of PcP during infliximab treatment, 3 of which died | For Crohn’s disease— Azathioprine and infliximab For PcP— Steroids and trimethoprim-sulfamethoxazole | Follow up 2 weeks later confirmed clinical response to therapy. | [11] |
Pustular psoriasis with an IL-36RN deficiency. | 1 M, 54 y PCP developed after infliximab | For pustular psoriasis— Cyclosporin which was unresponsive then Infliximab For PcP IV trimethoprim/ sulfamethoxazole | Mutation found in the IL36RN gene compatible with IL-36RN deficiency anakinra started and psoriasis improved | [12] |
Diabetes mellitus with pneumoconiosis and interstitial pneumonia | 1 M, 75 y Carcinoma of the buccal mucosa | Corticosteroids for interstitial pneumonia Trimethoprim/sulfamethoxazole and voriconazole for PcP and Aspergillus fumigatus | Died | [13] |
Systemic lupus erythematosus. | 5 cases Study of 858 hospitalized lupus patients. ID from lung biopsy in 2 and BAL in 3 | Prednisolone and concomitant biologics or immunosuppressants | 3 died | [9] |
Hyper-IgM syndrome | 1 M, 4 months | IgM syndrome diagnosis made after PcP was detected. trimethoprim/sulfamethoxazole for PcP | Recovered | [14] |
Membranoproliferative glomerulonephritis | 1 M, 50 y | Corticosteroids for underlying condition For PcP Trimethoprim/sulfamethoxazole | Recovered | [15] |
Dermatomyositis associated with anti-MDA-5 autoanti bodies | 2 M, 56 y Initially had interstitial lung disease without infection M, 52 y | Both treated with corticosteroids for underlying condition. Both had specific treatment for PcP M, 52 y also received cyclophosphamide bolus | Both died | [16] |
Cushing’s Syndrome | 15 13 developed PcP after initiation of cortisol blocking therapy. | Cushing’s syndrome—Cortisol blocking therapy PcP therapy—Not stated | 11 of the 15 patients died | [17] |
Pneumocystis jiroveci pneumonia after infliximab therapy: a review of 84 cases. | 84 Cases | 23 of the 84 patients died | [18] |
Clinical factor | Disease Classification | ||
---|---|---|---|
Mild | Moderate | Severe | |
Dysnoea | On exertion | On minimal exertion/possibly at rest | At rest |
Resting arterial tension | PaO2 of > 11.0 kPa | PaO2 8.1–11.0 kPa | PaO2 < 8.0 kPa |
Oxygen saturation | SaO2 > 96% | SaO2 of 91–96% | SaO2 < 91% |
Radiology | Normal/Minimal changes on CXR | Diffuse interstitial changes on CXR | Extensive interstitial changes with potential diffuse alveolar shadowing on CXR |
Other | Possibly Fever | Tachypnoea at rest, fever, cough |
Underlying Disease | Coinfection | Number of Cases/Medical History | Treatment | Outcome | Reference |
---|---|---|---|---|---|
COPD and chronic hepatitis C | PcP and Aspergillosis | 1 M, 95 y, treated for lung injury caused by Chlamydophila pnemonia | Ceftriaxone and Methylprednisolone Then alternating prednisolone and methylprednisolone Then meropenem and azithromycin. Then sulfamethoxazole/ trimethoprim for PcP Then levofloxacin, minocycline, liposomal amphotericin B along with PcP treatment | Died of multiple organ failure | [24] |
Crescentic IgA nephropathy and Non-Hodgkin lymphoma | PcP and Aspergillosis | 2 M, 29 y with crescentic IgA nephropathy on immunosuppressive drugs F, 72 y with non-Hodgkin lymphoma on chemotherapy | Both— Intravenous trimethroprim/sulphamethoxazole combined with voriconazole Prophylaxis M—Moxifloxacin and Ganciclovir F—Moxifloxacin and Valaciclovir | M—Recovered F—Died | [25] |
Alcoholic hepatitis and cirrhosis | PcP and cytomegalovirus | 1 M, 40 y | Initially broad spectrum antibiotics then prednisolone. Amphotericin B syrup dissolved in water gargled for oral and esophageal candidiasis No treatment for PCP, found during autopsy | Died of circulatory insufficiency | [26] |
Allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis | PcP, parainfluenza virus type 3, CMV and Aspergillus fumigatus. | 1 F, 63 y Presented with mucocutaneous macular skin rash with bulla. 3 months prior had an acute myocardial infarction. 1-month prior essential thrombocytosis 30 years previous had, surgery for intestinal TB and was a hepatitis C carrier. | High-dose systemic corticosteroids and intravenous immunoglobulin for Stevens-Johnson syndrome / toxic epidermal necrolysis 100 mg/day aspirin 1 mg/day anagrelide 200 mg/day allopurinol Anti-TB treatment 30 years ago. For co-infections Trimethroprim/sulphamethoxazole, voriconazole, ganciclovir and oral ribavirin. | Recovered | [27] |
Probable plasma cell myeloma | Streptococcal meningitis and PcP | 1 F, 64 y | Intravenous acyclovir, ceftriaxone and fluconazole for the meningitis Trimethroprim-sulfamethoxazole for PcP | Unclear | [28] |
HTLV-1 Associated Adult T-cell leukemia/lymphoma | PcP and Cryptococcus neoformans | 1 | Trimethroprim-sulfamethoxazole, corticosteroids and fluconazole | Recovered | [29] |
HIV | PcP and Strongyloides stercoralis | 1 M, 43 y | Trimethroprim-sulfamethoxazole, ivermectin and amphotericin B | Died | [30] |
Allogeneic hematopoietic stem cell transplantation recipient | PcP and Influenza A | 1 M, 53 y Immunosuppresive therapy for treatment of GVHD | For underlying condition - daily mycophenolate mofetil, tacrolimus and prophylactic Trimethroprim-sulfamethoxazole. Treated with high-dose corticosteroids for GVHD PCP prophylaxis switched to inhaled pentamidine due to pancytopenia attributed to Trimethroprim-sulfamethoxazole. PcP treated with Trimethroprim-sulfamethoxazole. | Recovered | [31] |
Infantile spasm | Legionella pneumophila and PcP | 1 8 month old infant | Not Stated | Died | [32] |
HIV | Mycobacterium tuberculosis and PcP | 1 | Trimethroprim-sulfamethoxazole prophylaxis for PcP Antituberculosis medication and Trimethroprim-sulfamethoxazole | Recovered | [33] |
Strategy | Population [Ref] | ||
---|---|---|---|
HIV-Positive [39] | Haematology [20,43] | Solid Organ Transplantation [44] | |
Prophylaxis | Front line: Trimethoprim/sulfamethoxazole one single-strength (80 mg TMP/400 mg SMX) daily or one double strength tablet (160 mg TMP/800 mg SMX)/daily. Second line: Trimethoprim/sulfamethoxazole one double strength tablet (160 mg TMP/800 mg SMX) three times per week Dapsone (50 mg twice daily) Dapsone (200 mg) + pyrimethamine (75 mg) + leucovorin (25 mg) weekly Dapsone (50 mg daily) + pyrimethamine (50 mg weekly) + leucovorin (25 mg weekly) Pentamidine aerosols (300 mg per month) Atovaquone 1500 mg daily | Front line: Trimethoprim/sulfamethoxazole one single-strength (80 mg TMP/400 mg SMX)/day or double strength tablet (160 mg TMP/800 mg SMX)/day or three per week. Second line: Dapsone (50 mg twice daily) Pentamidine aerosols (300 mg per month) Atovaquone (1500 mg daily) | Front line: Trimethoprim/sulfamethoxazole one single-strength (80 mg TMP/400 mg SMX)/day or double strength tablet (160 mg TMP/800 mg SMX)/day or three per week. Second line: Dapsone (50–100 mg once a day) Atovaquone (>1000 mg daily) Third Line: Pentamidine aerosols (300 mg every 3–4 weeks) |
Treatment | Frontline: Trimethoprim/sulfamethoxazole (15–20 mg/kg TMP; 75–100 mg/kg SMX per day) For moderate to severe disease (i.e., hypoxemia) adjunctive corticosteroids should be used Second line for severe disease: Primaquine and clindamycin (30 mg/(600 mg × 3)) per day Pentamidine IV (4 mg/kg/day) Second line for mild/moderate disease: Dapsone (100 mg daily) + trimethoprim (15 mg daily) Atovaquone (750 mg BID) | Frontline: Trimethoprim/sulfamethoxazole (15–20 mg/kg TMP; 75–100 mg/kg SMX per day) Second line: Primaquine and clindamycin (30 mg/(600 mg × 3)) per day Pentamidine IV (4 mg/kg/day) Atovaquone (750 mg/ 2–3 per day) | Frontline: Trimethoprim/sulfamethoxazole (15–20 mg/kg TMP; 75–100 mg/kg SMX per day) with TMP administered by IV every 6–8 h. For hypoxemic patients potentially in combination with 40–60 mg of prednisolone (twice daily) Second line: IV Pentamidine (Initially 4 mg/kg/day over 1–2 h) Recipients of pancreas/islet transplants should receive an alternative second line therapy. |
Underlying Disease | Number of Cases/ Medical History | Mechanism of Resistance | Alternative Treatment | Outcome | Reference |
---|---|---|---|---|---|
HIV | 1 M, 50 y | Mutations at codons 55 and 57 of the, associated with resistance to Trimethoprim/sulfamethoxazole. | Clindamycin-primaquine | Recovered | [103] |
HIV | 13 M = 11 F = 2 Each patient had 2 episodes | 3 patients had no PCP prophylaxis for both episodes only one had PcP mutations. 4 patients had no DHPS genotype mutations in their Positive PcP samples 9 patients had at least one of the mutations described below in their PcP samples M1, mutant 1 (Ala55 Pro57); M2, mutant 2 (Thr55 Ser57); M3, mutant 3 (Ala55 Ser57 double mutant). | Of the 11 patients who recovered, 9 received prophylaxis and all needed alternative therapy. | 1 with no prophylaxis died on Trimethoprim/sulfamethoxazole treatment, PcP mutations present. 1 with prophylaxis on 2nd presentation died after alternative therapy of Trimethoprim/sulfamethoxazole then pentamidine only had wild type PcP. 11 recovered. | [104] |
HIV | 152 | 31 of the 152 had Pnuemocystis carinii DHPS mutations These mutations were more common in patients who had previous exposure to sulpha drugs | Not available | Survival of patients with mutations was significantly lowered | [105] |
HIV and Non-HIV Immuno-suppressed | 56 46 HIV 10 Non-HIV Immuno-suppressed | Mutations in the DHPS gene | Not available | All HIV patients recovered 5 of the 10 Non-HIV patients died | [106] |
HIV | 1 M, 50 y No previous exposure to Trimethoprim/sulfamethoxazole | DHPS gene mutations at codon 55 and 57 (Thr55Ala and Pro57Ser) | Clindamycin-primaquine | Recovered | [107] |
Non-HIV Immunocompromised Patients | 18 | Substitution mutations: At DHPS codon 98—glutamate replaced by lysine. At DHPS codon 90—aspartate replaced by asparagine. | All patients received immunosuppressive agents but none of them received PcP prophylaxis For PcP— Trimethoprim/sulfamethoxazole Trimethoprim/sulfamethoxazole + Caspofungin Primaquine + clindamycin | Approximately 65% mortality | [108] |
HIV | 8 | Cytochrome b substitutions in the Qo region: T121I, L123F, T100I, I120V, S125A, P239L and L248F | 5 patients received Atovaquone prophylaxis, but 3 were Atovaquone naïve | 84% overall survival: 87% of patients with mutations survived | [76] |
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White, P.L.; Price, J.S.; Backx, M. Therapy and Management of Pneumocystis jirovecii Infection. J. Fungi 2018, 4, 127. https://doi.org/10.3390/jof4040127
White PL, Price JS, Backx M. Therapy and Management of Pneumocystis jirovecii Infection. Journal of Fungi. 2018; 4(4):127. https://doi.org/10.3390/jof4040127
Chicago/Turabian StyleWhite, P. Lewis, Jessica S. Price, and Matthijs Backx. 2018. "Therapy and Management of Pneumocystis jirovecii Infection" Journal of Fungi 4, no. 4: 127. https://doi.org/10.3390/jof4040127