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Open Forum Infectious Diseases Jan 2024Mucormycosis is a potentially lethal mycosis. We reviewed peer-reviewed publications on mucormycosis to assess therapeutic outcomes. (Review)
Review
BACKGROUND
Mucormycosis is a potentially lethal mycosis. We reviewed peer-reviewed publications on mucormycosis to assess therapeutic outcomes.
METHODS
A systematic literature search using the Ovid MEDLINE and EMBASE databases identified manuscripts describing human mucormycosis diagnosed according to European Organization for Research and Treatment of Cancer and the Mycoses Study Group criteria with therapeutic outcomes published from 2000 to 2022.
RESULTS
In 126 articles, 10 335 patients were described, most from Asia (n = 6632, 66%). Diabetes was the most frequent underlying disease (n = 6188, 60%); 222 (2.1%) patients had no underlying diseases. The dominant clinical form was rhino-orbitocerebral (n = 7159, 69.3%), followed by pulmonary (n = 1062, 10.3%). Of 5364 patients with outcome data, amphotericin B monotherapy (n = 3749, mortality 31.5%) was most frequent, followed by amphotericin B + azole (n = 843, mortality 6.6%; < .0001), amphotericin B followed by azole (n = 357, mortality 13.7%; < .0001), posaconazole only (n = 250, mortality 17.2%; < .0001), and isavuconazole only (n = 65, mortality 24.6%; = .24). Duration and dose of antifungals varied widely. Documented outcomes from surgical resections in 149 patients found that 47 of 125 died (37.6%), compared with 16 of 24 (66.7%) patients who did not undergo surgery ( = .008).
CONCLUSIONS
Mucormycosis is more frequently reported in Asia than in Europe and is often linked to diabetes. Antifungal therapy, usually with surgery, is frequently effective for mucormycosis.
PubMed: 38288347
DOI: 10.1093/ofid/ofad704 -
Ophthalmic Plastic and Reconstructive...Following COVID-19 infection a rising count of rhino-orbito-cerebral mucormycosis is observed, requiring orbital exenteration, a disabling lifetime affecting surgery....
PURPOSE
Following COVID-19 infection a rising count of rhino-orbito-cerebral mucormycosis is observed, requiring orbital exenteration, a disabling lifetime affecting surgery. One of the potential interventions for globe salvage in these patients is retrobulbar injections of amphotericin B. This study was conducted to review protocols, outcomes, and side effects of retrobulbar injection of amphotericin B in patients with COVID-19 associated rhino-orbito-cerebral mucormycosis (CAM).
METHODS
The PubMed, Scopus, Web of Science, and Embase databases were searched using a comprehensive string of relevant keywords. All English studies with the confirmed diagnosis of CAM infection were included. We excluded all studies in which retrobulbar injection of amphotericin B was not implemented in any of the patients or there was a lack of clarified and detailed data about this procedure among participants.
RESULTS
A total of 647 cases had a history of retrobulbar injection(s) of amphotericin B in 13 reviewed studies with 3,132 subjects of CAM. The most common protocol was the retrobulbar injection of 1 ml of 3.5 mg/ml liposomal amphotericin B for 3 doses daily or on alternate days. We discerned that the globe salvage rate was 95.0% in eyes with a history of retrobulbar injection(s). The total rate of orbital exenteration was 14.9%, regardless of the history of retrobulbar injection of the drug. Other outcomes of this intervention were vision salvage and reduced major ophthalmic complaints, including pain, swelling, chemosis, ptosis, and ophthalmoplegia. The side effects of this intervention were not serious, and most of them were transient. They included swelling at the injection site, restriction of ocular motilities, exacerbation of orbital inflammation, and even intensification of visual impairment in a few cases.
CONCLUSIONS
Retrobulbar injection of amphotericin B should be considered a nearly safe and protective intervention against orbital exenteration in patients with CAM. It may also be effective in saving vision. Since the effectiveness of orbital exenteration in the survival of patients is not ascertained, retrobulbar injections can be considered an alternative intervention.
Topics: Amphotericin B; Antifungal Agents; COVID-19; Eye Diseases; Eye Infections, Fungal; Humans; Mucormycosis; Orbital Diseases; Paranasal Sinus Diseases
PubMed: 35943425
DOI: 10.1097/IOP.0000000000002256 -
The Cochrane Database of Systematic... Sep 2014Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although its effect seems... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although its effect seems to be equivocal.
OBJECTIVES
To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency.
SEARCH METHODS
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
SELECTION CRITERIA
Randomised clinical trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B.
DATA COLLECTION AND ANALYSIS
Data on mortality, invasive fungal infection and colonisation were independently extracted by both authors. A random-effects model was used unless the P value was greater than 0.10 for the test of heterogeneity.
MAIN RESULTS
We included 14 trials (1569 patients). The drugs were given prophylactically in 12 trials and as treatment in two. Eleven trials were in acute leukaemia, solid cancer, or bone marrow recipients; one in liver transplant patients; one in critically ill surgical and trauma patients; and one in AIDS patients. Nystatin was compared with placebo in three trials, with fluconazole in 10, and amphotericin B in one; the dose varied from 0.8 MIE to 72 MIE daily and was 2 mg/kg/d in a liposomal formulation. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk (RR) 0.85, 95% confidence interval (CI) 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (RR 0.75, 95% CI 0.54 to 1.03) whereas fluconazole was more effective in preventing invasive fungal infection (RR 0.40, 95% CI 0.17 to 0.93) and colonisation (RR 0.50, 95% CI 0.36 to 0.68). There were no proven fungal infections in a small trial that compared amphotericin B with liposomal nystatin. The results were very similar if the three studies that were not performed in cancer patients were excluded. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Nystatin cannot be recommended for prophylaxis or the treatment of Candida infections in immunodepressed patients.
Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candidiasis; Fluconazole; Humans; Immunocompromised Host; Liposomes; Mycoses; Nystatin; Opportunistic Infections; Randomized Controlled Trials as Topic
PubMed: 25188770
DOI: 10.1002/14651858.CD002033.pub2 -
The Cochrane Database of Systematic... Sep 2014Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.
OBJECTIVES
To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.
SEARCH METHODS
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
SELECTION CRITERIA
Randomised clinical trials comparing fluconazole with amphotericin B.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
MAIN RESULTS
Seventeen trials (3798 patients, 381 deaths) were included. In two large three-armed trials, results for amphotericin B were combined with results for nystatin in a 'polyene' group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the 'polyene' trials but we were unable to obtain any information from the trial authors or from Pfizer, the manufacturer of fluconazole, to clarify these issues. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion-related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.
Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Injections, Intravenous; Mycoses; Neoplasms; Neutropenia; Nystatin; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 25188769
DOI: 10.1002/14651858.CD000239.pub2 -
Italian Journal of Pediatrics Mar 2023Invasive pulmonary aspergillosis (IPA) is a severe condition in immunocompromised children, but the optimal management is still under debate. In order to better clarify... (Review)
Review
Invasive pulmonary aspergillosis (IPA) is a severe condition in immunocompromised children, but the optimal management is still under debate. In order to better clarify this issue, a literature search was performed through MEDLINE/PubMed database to describe current risk factors and diagnostic, therapeutic and prophylactic tools for invasive pulmonary aspergillosis (IPA) in the paediatric age. Observational studies and clinical trials regarding diagnosis, treatment and prophylaxis were considered, and results were summarised. Five clinical trials and 25 observational studies (4453 patients) were included.Haematological malignancies, previous organ transplant and other primary or acquired immunodeficiency were identified as risk factors for IPA in children.Current diagnostic criteria distinguish between "proven", "probable" and "possible" disease. Consecutive galactomannan assays have good sensitivity and specificity, especially when performed on broncho-alveolar lavage. At the same time, β-D-glucan should not be used since cut-off in children is unclear. PCR assays cannot currently be recommended for routine use.Voriconazole is the recommended first-line agent for IPA in children older than 2 years of age. Liposomal amphotericin B is preferred in younger patients or cases of intolerance to voriconazole. Its plasma concentrations should be monitored throughout the treatment. The optimal duration of therapy has yet to be determined. Posaconazole is the preferred prophylactic agent in children older than 13 years old, whereas oral voriconazole or itraconazole are the drugs of choice for those between 2-12 years. Further good-quality studies are warranted to improve clinical practice.
Topics: Humans; Child; Child, Preschool; Adolescent; Invasive Pulmonary Aspergillosis; Voriconazole; Pulmonary Aspergillosis; Sensitivity and Specificity; Immunocompromised Host; Mannans; Antifungal Agents
PubMed: 36978151
DOI: 10.1186/s13052-023-01440-9 -
The Cochrane Database of Systematic... Feb 2014Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and therapeutically in these patients.
OBJECTIVES
To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.
SEARCH METHODS
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were accepted. Contact was made with trial authors and industry.
SELECTION CRITERIA
Randomised clinical trials comparing voriconazole with amphotericin B or fluconazole.
DATA COLLECTION AND ANALYSIS
Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted independently by two review authors.
MAIN RESULTS
Three trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infection) in neutropenic cancer patients (849 patients, 58 deaths). The second trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). The third trial compared fluconazole to voriconazole for prophylaxis of fungal infections in patients receiving allogeneic stem cell transplantation (600 patients, number of deaths not stated). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the trial authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from the analysis by the trial authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication to counter side effects and replacement of electrolytes or use of salt water. This choice of comparator resulted in a marked difference in the duration of treatment on the trial drugs (77 days with voriconazole versus 10 days with amphotericin B) and precluded meaningful comparisons of the benefits and harms of the two drugs. The third trial failed to find a difference in fungal free survival or invasive fungal infections at 180 days when voriconazole was compared to fluconazole.
AUTHORS' CONCLUSIONS
Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of fungal infections in neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions. For prophylactic fungal treatment in patients receiving allogeneic stem cell transplantation, there was no difference between voriconazole and fluconazole regarding fungal free survival or invasive fungal infections.
Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fluconazole; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole
PubMed: 24563222
DOI: 10.1002/14651858.CD004707.pub3 -
The Cochrane Database of Systematic... Apr 2015Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income countries. Although there are medications available, their effectiveness is unclear.
OBJECTIVES
To assess the effects of different antifungal drugs in the management of fungal keratitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2015), EMBASE (January 1980 to March 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 March 2015.
SELECTION CRITERIA
We included randomised controlled trials of medical therapy for fungal keratitis.
DATA COLLECTION AND ANALYSIS
Two review authors selected studies for inclusion in the review, assessed trials for risk of bias and extracted data. The primary outcome was clinical cure at two to three months. Secondary outcomes included best-corrected visual acuity, time to clinical cure, compliance with treatment, adverse outcomes and quality of life.
MAIN RESULTS
We included 12 trials in this review; 10 trials were conducted in India, one in Bangladesh and one in Egypt. Seven of these trials were at high risk of bias in one or more domains, two of these studies were at low risk of bias in all domains. Participants were randomised to the following comparisons: topical 5% natamycin compared to topical 1% voriconazole; topical 5% natamycin compared to topical 2% econazole; topical 5% natamycin compared to topical chlorhexidine gluconate (0.05%, 0.1% and 0.2%); topical 1% voriconazole compared to intrastromal voriconazole 50 g/0.1 mL (both treatments combined with topical 5% natamycin); topical 1% voriconazole combined with oral voriconazole compared to both oral voriconazole and oral itraconazole (both combined with topical 5% natamycin); topical 1% itraconazole compared to topical 1% itraconazole combined with oral itraconazole; topical amphotericin B compared to topical amphotericin B combined with subconjunctival injection of fluconazole; intracameral injection of amphotericin B with conventional treatment compared to conventional treatment alone (severe fungal ulcers); topical 0.5% and 1% silver sulphadiazine compared to topical 1% miconazole. Overall the results were inconclusive because for most comparisons only one small trial was available. The exception was the comparison of topical natamycin and topical voriconazole for which three trials were available. In one of these trials clinical cure (healed ulcer) was reported in all 15 people allocated to natamycin and in 14/15 people allocated to voriconazole (risk ratio (RR) 1.07; 95% confidence interval (CI) 0.89 to 1.28, low quality evidence). In one trial people randomised to natamycin were more likely to have a microbiological cure at six days (RR 1.64; 95% CI 1.38 to 1.94, 299 participants). On average, people randomised to natamycin had better spectacle-corrected visual acuity at two to three months compared to people randomised to voriconazole but the estimate was uncertain and the 95% confidence intervals included 0 (no difference) (mean difference -0.12 logMAR, 95% CI -0.31 to 0.06, 434 participants; 3 studies, low quality evidence) and a decreased risk of corneal perforation or therapeutic penetrating keratoplasty, or both (RR 0.61; 95% CI 0.40 to 0.94, 434 participants, high quality evidence). There was inconclusive evidence on time to clinical cure. Compliance with treatment and quality of life were not reported. One trial comparing natamycin and voriconazole found the effect of treatment greater in Fusarium species, but this subgroup analysis was not prespecified by this review.
AUTHORS' CONCLUSIONS
The trials included in this review were of variable quality and were generally underpowered. There is evidence that natamycin is more effective than voriconazole in the treatment of fungal ulcers. Future research should evaluate treatment effects according to fungus species.
Topics: Antifungal Agents; Eye Infections, Fungal; Humans; Keratitis; Natamycin; Randomized Controlled Trials as Topic; Voriconazole
PubMed: 25855311
DOI: 10.1002/14651858.CD004241.pub4 -
Tropical Medicine and Infectious Disease Aug 2022A reliable estimate of antifungal susceptibility in candidemia patients is increasingly important to track the spread of bloodstream infections and define the true... (Review)
Review
A reliable estimate of antifungal susceptibility in candidemia patients is increasingly important to track the spread of bloodstream infections and define the true burden of the ongoing antifungal resistance. A systematic review and meta-analysis (SRMA) were conducted aiming to estimate the global prevalence and identify patterns of antifungal resistance. A systematic literature search of the PubMed, Scopus, ScienceDirect and Google Scholar electronic databases was conducted on published studies that employed antifungal susceptibility testing (AFST) on clinical isolates globally. Seventy-nine eligible studies were included. Using meta-analysis of proportions, the overall pooled prevalence of three most important antifungal drugs; Fluconazole, Amphotericin B and Voriconazole resistant were calculated as 15.2% (95% CI: 9.2-21.2), 1.3% (95% CI: 0.0-2.9) and 4.7% (95% CI: 2.2-7.3), respectively. Based on study enrolment time, country/continent and AFST method, subgroup analyses were conducted for the three studied antifungals to determine sources of heterogeneity. Timeline and regional differences in prevalence of antifungal resistance were identified with the same patterns among the three antifungal drugs. These findings highlight the need to conduct further studies to assess and monitor the growing burden of antifungal resistance, to revise treatment guidelines and to implement regional surveillance to prevent further increase in drug resistance emerging recently.
PubMed: 36006280
DOI: 10.3390/tropicalmed7080188 -
The Cochrane Database of Systematic... Jul 2018Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths worldwide. The best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis is unclear, particularly in resource-limited settings where management of drug-related toxicities associated with more potent antifungal drugs is a challenge.
OBJECTIVES
To evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis; to compare side effect profiles of different therapies.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE (PubMed), Embase (Ovid), LILACS (BIREME), African Index Medicus, and Index Medicus for the South-East Asia Region (IMSEAR) from 1 January 1980 to 9 July 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the ISRCTN registry; and abstracts of select conferences published between 1 July 2014 and 9 July 2018.
SELECTION CRITERIA
We included randomized controlled trials that compared antifungal induction therapies used for the first episode of HIV-associated cryptococcal meningitis. Comparisons could include different individual or combination therapies, or the same antifungal therapies with differing durations of induction (less than two weeks or two or more weeks, the latter being the current standard of care). We included data regardless of age, geographical region, or drug dosage. We specified no language restriction.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardized forms. The main outcomes included mortality at 2 weeks, 10 weeks, and 6 months; mean rate of cerebrospinal fluid fungal clearance in the first two weeks of treatment; and Division of AIDS (DAIDS) grade three or four laboratory events. Using random-effects models we determined pooled risk ratio (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean differences (MD) and 95% CI for continuous outcomes. For the direct comparison of 10-week mortality, we assessed the certainty of the evidence using the GRADE approach. We performed a network meta-analysis using multivariate meta-regression. We modelled treatment differences (RR and 95% CI) and determined treatment rankings for two-week and 10-week mortality outcomes using surface under the cumulative ranking curve (SUCRA). We assessed transitivity by comparing distribution of effect modifiers between studies, local inconsistency through a node-splitting approach, and global inconsistency using design-by-treatment interaction modelling. For the network meta-analysis, we applied a modified GRADE approach for assessing the certainty of the evidence for 10-week mortality.
MAIN RESULTS
We included 13 eligible studies that enrolled 2426 participants and compared 21 interventions. All studies were carried out in adults, and all but two studies were conducted in resource-limited settings, including 11 of 12 studies with 10-week mortality data.In the direct pairwise comparisons evaluating 10-week mortality, one study from four sub-Saharan African countries contributed data to several key comparisons. At 10 weeks these data showed that those on the regimen of one-week amphotericin B deoxycholate (AmBd) and flucytosine (5FC) followed by fluconazole (FLU) on days 8 to 14 had lower mortality when compared to (i) two weeks of AmBd and 5FC (RR 0.62, 95% CI 0.42 to 0.93; 228 participants, 1 study), (ii) two weeks of AmBd and FLU (RR 0.58, 95% CI 0.39 to 0.86; 227 participants, 1 study), (iii) one week of AmBd with two weeks of FLU (RR 0.49, 95% CI 0.34 to 0.72; 224 participants, 1 study), and (iv) two weeks of 5FC and FLU (RR 0.68, 95% CI 0.47 to 0.99; 338 participants, 1 study). The evidence for each of these comparisons was of moderate certainty. For other outcomes, this shortened one-week AmBd and 5FC regimen had similar fungal clearance (MD 0.05 log CFU/mL/day, 95% CI -0.02 to 0.12; 186 participants, 1 study) as well as lower risk of grade three or four anaemia (RR 0.31, 95% CI 0.16 to 0.60; 228 participants, 1 study) compared to the two-week regimen of AmBd and 5FC.For 10-week mortality, the comparison of two weeks of 5FC and FLU with two weeks of AmBd and 5FC (RR 0.92, 95% CI 0.69 to 1.23; 340 participants, 1 study) or two weeks of AmBd and FLU (RR 0.85, 95% CI 0.64 to 1.13; 339 participants, 1 study) did not show a difference in mortality, with moderate-certainty evidence for both comparisons.When two weeks of combination AmBd and 5FC was compared with AmBd alone, pooled data showed lower mortality at 10 weeks (RR 0.66, 95% CI 0.46 to 0.95; 231 participants, 2 studies, moderate-certainty evidence).When two weeks of AmBd and FLU was compared to AmBd alone, there was no difference in 10-week mortality in pooled data (RR 0.94, 95% CI 0.55 to 1.62; 371 participants, 3 studies, low-certainty evidence).One week of AmBd and 5FC followed by FLU on days 8 to 14 was the best induction therapy regimen after comparison with 11 other regimens for 10-week mortality in the network meta-analysis, with an overall SUCRA ranking of 88%.
AUTHORS' CONCLUSIONS
In resource-limited settings, one-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis. An all-oral regimen of two weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered. We found no mortality benefit of combination two weeks AmBd and FLU compared to AmBd alone. Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings.
Topics: Acetazolamide; Acute Disease; Adult; Amphotericin B; Antifungal Agents; Developing Countries; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Health Resources; Humans; Induction Chemotherapy; Intracranial Hypertension; Meningitis, Cryptococcal; Network Meta-Analysis
PubMed: 30045416
DOI: 10.1002/14651858.CD005647.pub3 -
Medical Mycology Oct 2017Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this... (Review)
Review
Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014. Among 34 patients with median age 41 (0.5-73 years), 24 (71%) were males. While 12 (35%) were immunocompromised patients, 14 (41%) had prior surgery, and seven (21%) suffered trauma. Other underlying conditions included diabetes mellitus, hematological malignancies, transplantation, and corticosteroid therapy. The median diagnostic delay from onset of symptoms and signs was 60 (10-180) days. The principal mechanism of the infection was direct inoculation (n = 19; 56%), and in immunocompromised patients was usually hematogenous disseminated. The long bones were infected by trauma or surgery, while a wide variety of bones were involved by hematogenous dissemination. Combined surgery and amphotericin B treatment were implemented in 28 (82%) and eight (23%) had an unfavorable outcome. Osteoarticular mucormycosis occurs most frequently after trauma or surgical procedures. These infections are progressively destructive and more virulent in individuals with impaired immune systems. Early diagnosis, timely administration of amphotericin B, control of underlying conditions, and surgical debridement of infected tissue are critical for successful management of osteoarticular mucormycosis.
Topics: Adolescent; Adult; Aged; Antifungal Agents; Arthritis; Child; Child, Preschool; Debridement; Early Diagnosis; Female; Humans; Infant; Male; Middle Aged; Mucorales; Mucormycosis; Osteomyelitis; Surgical Wound Infection; Wounds and Injuries; Young Adult
PubMed: 28053147
DOI: 10.1093/mmy/myw136