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Journal Der Deutschen Dermatologischen... Jun 2024Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal... (Review)
Review
Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases "PubMed" and "Lilacs" from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.
Topics: Humans; Leishmaniasis, Mucocutaneous; Antiprotozoal Agents
PubMed: 38769082
DOI: 10.1111/ddg.15424 -
Journal of Acquired Immune Deficiency... May 2008Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). (Review)
Review
BACKGROUND
Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP).
METHODS
We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007 and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs).
RESULTS
Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82 individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3.2] and 2.7 [95% CI: 1.3 to 4.0], respectively) but were considerably lower for intravenous pentamidine (44%; OR = 0.8 [95% CI: 0.6 to 1.0]).
CONCLUSIONS
Clindamycin-primaquine is an alternative to intravenous pentamidine as second-line treatment for PCP in patients who fail treatment with TMP-SMX. TMP-SMX should be used as a second-line treatment for those failing first-line treatments with regimens other than TMP-SMX.
Topics: AIDS-Related Opportunistic Infections; Clindamycin; Cohort Studies; Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Salvage Therapy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 18360286
DOI: 10.1097/QAI.0b013e31816de84d -
PLoS Neglected Tropical Diseases Mar 2016Leishmania aethiopica is the etiological agent of cutaneous leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL),... (Review)
Review
Leishmania aethiopica is the etiological agent of cutaneous leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL that can be taken forward for clinical trials. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials (n = 201), pentamidine (n = 150) and cryotherapy (n = 103). There were 20 case reports/series, with an overall poor study quality. We only identified two small and/or poor quality randomized controlled trials conducted a long time ago. There were two prospective non-randomized studies reporting on cryotherapy, antimonials and pentamidine. With cryotherapy, cure rates were 60-80%, and 69-85% with antimonials. Pentamidine appeared effective against complicated CL, also in cases non-responsive to antimonials. However, all studies suffered from methodological limitations. Data on miltefosine, paromomycin and liposomal amphotericin B are extremely scarce. Only a few studies are available on DCL. The only potentially effective treatment options for DCL seem to be antimonials with paromomycin in combination or pentamidine, but none have been properly evaluated. In conclusion, the evidence-base for treatment of complicated CL due to L aethiopica is extremely limited. While antimonials remain the most available CL treatment in Ethiopia, their efficacy and safety in CL should be better defined. Most importantly, alternative first line treatments (such as miltefosine or paromomycin) should be explored. High quality trials on CL due to L aethiopica are urgently needed, exploring group sequential methods to evaluate several options in parallel.
Topics: Adolescent; Adult; Aged; Antiprotozoal Agents; Child; Child, Preschool; Cryotherapy; Ethiopia; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult
PubMed: 26938448
DOI: 10.1371/journal.pntd.0004495 -
Einstein (Sao Paulo, Brazil) 2014In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when... (Review)
Review
In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes.
Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Comorbidity; Female; Humans; Male; Pancreatitis; Risk Factors
PubMed: 24728257
DOI: 10.1590/s1679-45082014rw2561 -
The Journal of Clinical Endocrinology... Mar 2009Drug-induced hypoglycemia is a significant adverse effect that may cause important morbidity. (Review)
Review
CONTEXT
Drug-induced hypoglycemia is a significant adverse effect that may cause important morbidity.
OBJECTIVE
The aim of the study was to systematically review the literature for drugs reported to cause hypoglycemia and assess the quality of evidence and strength of association supporting this causal link.
DATA SOURCES
We searched electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) and the drug information system Micromedex through November 2007 and sought additional references from experts.
STUDY SELECTION
Studies were eligible if they reported hypoglycemia as a side effect of a drug not used to treat hyperglycemia, regardless of their design, language, size, or follow-up duration. We excluded hypoglycemia caused by industrial exposures, nonpharmacological chemical exposures, alcohol, herbs, nutritional supplements, and in vitro and animal studies.
DATA EXTRACTION
Reviewers extracted study characteristics and methodological quality and, when possible, data to estimate the odds of developing hypoglycemia when exposed to the offending agent.
DATA SYNTHESIS
We found 448 eligible studies that described 2696 cases of hypoglycemia associated with 164 different drugs. The quality of evidence supporting associations between drugs and hypoglycemia was mostly very low due to methodological limitations and imprecision. The most commonly reported offending drugs were quinolones, pentamidine, quinine, beta blockers, angiotensin-converting enzyme agents, and IGF.
CONCLUSIONS
Very low quality evidence substantiates the association between hypoglycemia and the use of numerous nondiabetic drugs.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypoglycemia; Infant; Infant, Newborn; Male; Middle Aged
PubMed: 19088166
DOI: 10.1210/jc.2008-1416 -
The American Journal of Tropical... Aug 2007Mucosal leishmaniasis (ML) is an important endemic disease and public-health problem in underdeveloped countries because of its significant morbidity and mortality.... (Review)
Review
Mucosal leishmaniasis (ML) is an important endemic disease and public-health problem in underdeveloped countries because of its significant morbidity and mortality. Increases in ecological tourism have extended this problem to developed countries. This form of leishmaniasis, caused by reactivation after primary cutaneous lesion, has a natural history of progressive destruction of the nasal septa and soft and hard palates, causing facial disfiguration and leading to respiratory disturbances. Treatment of ML, based on several therapies, depends on use of toxic compounds, and few drugs have emerged over the past 40 years. Drug resistance has increased, and the cure rate is no better than 70% in the largest studies. Despite these data, there has been no systematic review of therapies used to treat this important tropical disease. The aim of this study is to determine the best drug management for treatment of ML in Latin America based on the best studies offered by the medical literature. The MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to ML and therapy. The studies were independently selected by 2 authors. Articles with sufficient data for cure and treatment failures, internal and external validity information, and > 4 patients in each treatment were included. Validation of this systematic review was based on guidelines to guarantee quality; 22 articles met our inclusion criteria. Stibogluconate achieved a 51% cure rate (76/150 patients), and 88% of patients treated with meglumine were cured (121 patients). Pentamidine and amphotericin were as effective as meglumine. Use of itraconazole and other therapies (pentoxifylline, allopurinol, or interferon-gamma) was controversial, and numbers of patients in some studies were insufficient for statistical analysis. Meglumine may be the drug of choice in the treatment of ML, as it offers similar cure rates when compared with amphotericin B and pentamidine. Cost, adverse effects, local experience, and availability of drugs to treat ML are strong points to be considered before determining the best management of this disease, especially in developing countries.
Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Itraconazole; Latin America; Leishmania; Leishmaniasis, Mucocutaneous; Meglumine; Paromomycin; Pentamidine
PubMed: 17690398
DOI: No ID Found -
The Cochrane Database of Systematic... Jul 2006Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality.
OBJECTIVES
To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air).
SEARCH STRATEGY
We searched Medline (January 1980-December 2004), EMBASE (January 1985-December 2004) and The Cochrane Library (Issue 4, 2004) without language restrictions to identify randomised controlled trials that compared adjunctive corticosteroids to control in HIV-infected patients with PCP. We further reviewed the reference lists from previously published overviews, we searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts of the field, and searched reference lists of identified publications for citations of additional relevant articles.
SELECTION CRITERIA
Trials were considered eligible for this review if they compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, used random allocation, and reported mortality data. We excluded trials in patients with no or mild hypoxemia (arterial oxygen partial pressure >70 mmHg or an alveolar-arterial gradient <35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS
Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups by using a random effects model.
MAIN RESULTS
Six studies were included in the review and meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval [CI], 0.32-0.98) at 1 month and 0.68 (95% CI, 0.50-0.94) at 3-4 months of follow-up. To prevent 1 death, numbers needed to treat are 9 patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.38 (95% CI, 0.20-0.73) in favour of adjunctive corticosteroids.
AUTHORS' CONCLUSIONS
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but evidence from this review suggests a beneficial effect for patients with substantial hypoxemia.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Chemotherapy, Adjuvant; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 16856118
DOI: 10.1002/14651858.CD006150 -
The Cochrane Database of Systematic... Apr 2009Pentavalent antimonial drugs are the most prescribed treatment for American cutaneous and mucocutaneous leishmaniasis. Other drugs have been used with varying success. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pentavalent antimonial drugs are the most prescribed treatment for American cutaneous and mucocutaneous leishmaniasis. Other drugs have been used with varying success.
OBJECTIVES
To assess the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis.
SEARCH STRATEGY
We searched the Cochrane Skin Group Specialised Register (January 2009), the Register of Controlled Clinical Trials in The Cochrane Library (Issue 1,2009), MEDLINE (2003 to January 2009), EMBASE (2005 to January 2009), LILACS (from inception to January 2009), CINAHL (1982-May 2007) and other databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing treatments for American cutaneous and mucocutaneous leishmaniasis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data.
MAIN RESULTS
We included 38 trials involving 2728 participants. Results are based on individual studies or limited pooled analyses. There was good evidence in:Leishmania braziliensis and L. panamensis infections:Intramuscular (IM) meglumine antimoniate (MA) was better than oral allopurinol for 28 days (1RCT n=127, RR 0.39; 95% CI 0.26, 0.58). Intravenous (IV)MA for 20-days was better than 3-day and 7-day IVMA plus 15% paromomycin plus 12% methylbenzethonium chloride (PR-MBCL) or 7-day IVMA (1RCT n= 150, RR 0.24; 95% CI 0.11, 0.50; RR 0.69; 95% CI 0.53, 0.90; RR 0.64; 95% CI 0.44, 0.92 respectively). Oral allopurinol plus antimonials was better than IV antimonials (2RCT n= 168, RR 1.90; 95% CI 1.40, 2.59; I(2)=0%).L. braziliensis infections:Oral pentoxifylline plus IV sodium stibogluconate (SSG) was better than IVSSG (1RCT n= 23, RR 1.66; 95% CI 1.03, 2.69); IVMA was better than IM aminosidine sulphate (1RCT n= 38, RR 0.05; 95% CI 0.00, 0.78) and better than IV pentamidine isethionate (1RCT n= 80, RR 0.45; 95% CI 0.29, 0.71). Intramuscular MA was better than Bacillus Calmette-Guérin (1RCT n= 93, RR 0.46; 95% CI 0.32, 0.65).L .panamensis infections:Oral allopurinol was better than IVMA (1RCT n= 58, RR 2.20; 95% CI 1.34, 3.60). Aminosidine sulphate at doses of 12 mg/kg/day and 18 mg/kg/day for 14 days were better than aminosidine sulphate 12 mg/kg/day for 7 days (1RCT n= 60, RR 0.23; 95% CI 0.07, 0.73; RR 0.23; 95% CI 0.07, 0.73 respectively). Oral ketoconazole for 28 days, oral miltefosine and topical PR-MBCL were better than placebo.
AUTHORS' CONCLUSIONS
Most trials have been designed and reported so poorly that they are inconclusive. There is a need for large well conducted studies that evaluate long-term effects of current therapies to improve quality and standardization of methods.
Topics: Administration, Oral; Antiprotozoal Agents; BCG Vaccine; Humans; Hyperthermia, Induced; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Randomized Controlled Trials as Topic
PubMed: 19370612
DOI: 10.1002/14651858.CD004834.pub2 -
BMJ Clinical Evidence Jul 2008Pneumocystis pneumonia (PCP) is a common AIDS-defining opportunistic illness in people with HIV infection, but its incidence has fallen with use of prophylactic... (Review)
Review
INTRODUCTION
Pneumocystis pneumonia (PCP) is a common AIDS-defining opportunistic illness in people with HIV infection, but its incidence has fallen with use of prophylactic treatment. Without treatment, PCP is likely to be fatal in people with AIDS, so placebo-controlled studies would be considered unethical.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of adjuvant corticosteroids in people receiving first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of treatments for Pneumocystis pneumonia in people infected with HIV who have not responded to first-line antipneumocystis treatment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adjuvant corticosteroids, aerosolised or intravenous pentamidine, atovaquone, clindamycin-primaquone, treatment after failure of first-line treatment, trimethoprim-dapsone, and trimethoprim-sulfamethoxazole (TMP-SMX, co-trimoxazole).
Topics: AIDS-Related Opportunistic Infections; Administration, Oral; Adrenal Cortex Hormones; Atovaquone; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 19445734
DOI: No ID Found -
The Lancet. Infectious Diseases Dec 2005The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with... (Comparative Study)
Comparative Study Review
The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with different treatments between 1980 and 2004. Overall, 53 studies were included (all but one published), of which 15 were comparative (randomised, quasi-randomised, or non-randomised), 23 dose-finding, and 15 non-comparative. Data from comparative studies were pooled when appropriate for meta-analysis. Overall, these studies enrolled 7263 patients in 123 treatment arms. Adequacy of methods used to do the studies and report on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony must now be replaced, despite attempts to stop its progression by increasing dose and duration of therapy. The classic second-line treatments are unsuited: pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalisation for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price. Miltefosine-the first oral drug for visceral leishmaniasis-is now registered and marketed in India and is effective, but should be used under supervision to prevent misuse. Paromomycin (or aminosidine) is effective and safe, and although not yet available, a regulatory submission is due soon. To preserve the limited armamentarium of drugs to treat visceral leishmaniasis, drugs should not be deployed unprotected; combinations can make drugs last longer, improve treatment, and reduce costs to households and health systems. India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere.
Topics: Animals; Antimony; Antiprotozoal Agents; Child; Clinical Trials as Topic; Drug Resistance; Humans; India; Leishmania donovani; Leishmaniasis, Visceral; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 16310148
DOI: 10.1016/S1473-3099(05)70296-6