High-dose Trimethoprim-sulfamethoxazole Research Articles

Trimethoprim-sulfamethoxazole dosing and outcomes of pulmonary nocardiosis.

Nocardia often causes pulmonary infection among those with chronic pulmonary disease or immunocompromising conditions. Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as first-line treatment, though little data exists regarding outcomes of different dosing regimens. We performed a multicenter retrospective cohort study of adult patients with non-disseminated pulmonary nocardiosis initially treated with TMP-SMX monotherapy. Patients' initial TMP-SMX dosing was categorized as high- (> 10mg/kg/day), intermediate- (5-10mg/kg/day) or low-dose (< 5mg/kg/day). Outcomes included one-year mortality, post-treatment recurrence, and dose adjustment or early discontinuation of TMP-SMX. SMX serum concentrations and their effect on management were also assessed. Inverse probability of treatment weighting was applied to Cox regression analyses. Ninety-one patients were included with 24 (26.4%), 37 (40.7%), and 30 (33.0%) treated with high-, intermediate-, and low-dose TMP-SMX, respectively. Patients who initially received low-dose (HR 0.07, 95% CI 0.01-0.68) and intermediate-dose TMP-SMX (HR 0.27, 95% CI 0.07-1.04) had lower risk of one-year mortality than the high-dose group. Risk of recurrence was similar between groups. Nineteen patients had peak SMX serum concentrations measured which resulted in 7 (36.8%) dose changes and was not associated with one-year mortality or recurrence. However, 66.7% of the high-dose group required TMP-SMX dose adjustment/discontinuation compared to 24.3% of the intermediate-dose and 26.7% of the low-dose groups (p = 0.001). Low- and intermediate-dose TMP-SMX for non-disseminated pulmonary nocardiosis were not associated with poor outcomes compared to high-dose therapy, which had a higher rate of dose adjustment/early discontinuation. Historically used high-dose TMP-SMX may not be necessary for management of isolated pulmonary nocardiosis.

Fever of unknown origin revealing testicular nocardiosis: a case report and literature review

BackgroundNocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis.Case presentationWe report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient’s condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis.ConclusionsTo the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

Pneumocystis jirovecii pneumonia in people living with HIV: a review.

SUMMARYPneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

225. Risk Factors for Mortality in Stenotrophomonas Bacteremia: A Retrospective Study

Abstract Background Stenotrophomonas is a gram-negative organism typically associated with nosocomial infections. It is an emerging multi-drug resistant pathogen associated with significant morbidity and mortality in hospitalized patients. Optimal therapy is unknown. In this study, we evaluated the impact of treatment agent, dosing regimen, and patient characteristics on 30-day mortality for Stenotrophomonas bacteremia in our hospital system. Methods Retrospective chart review from April 2013 to September 2019 at Ronald Reagan and Santa Monica UCLA Medical Centers in Los Angeles, California. Adult patients who were hospitalized and received active therapy for Stenotrophomonas bacteremia were included in the study. Chi-square or Fischer test was used for categorical variables, Student’s t-test or Mann-Whitney U test was used for continuous variables. Results Sixty-nine patients were included in the study. The median age was 53 and 31 patients (44.9%) were female. Central line associated infections were the most common source of infection (79.7%, n = 55). Two patients (3%) had a relapse of infection. The overall 30-day mortality was 30.4% (n=21). The patients who did not survive to 30 days tended to have a higher Pitt bacteremia score, a longer length of stay, and were more likely to have used other antibiotics in the 30 days prior to culture collection. Trimethoprim-sulfamethoxazole (TMP-SMX) was the most common antibiotic used for treatment (n = 45, 65.2%). Of the patients who were treated with TMP-SMX, 19 were treated with high-dose (defined as 15 mg/kg or equivalent) and 26 had an alternative dosage after adjusting for renal function. There was no difference in 30-day mortality in the TMP-SMX high dose vs alternative dose (42.1% vs 30.8%, p = 0.53). Conclusion Stenotrophomonas bacteremia was associated with high mortality. High-dose TMP-SMX did not impact survival in our study; however, this may be due to small sample size. More research is needed to determine optimal therapy. Disclosures All Authors: No reported disclosures

56. High Frequencies of Adverse Drug Events with Intravenous vs Oral High-Dose Trimethoprim-Sulfamethoxazole: An Opportunity for Antibiotic Stewardship

BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) is a high-bioavailability antibiotic associated with potentially serious adverse drug events (ADE). The objective of this study was to evaluate the safety of intravenous (IV) and oral (PO) high-dose TMP-SMX.MethodsIRB-approved retrospective cohort of hospitalized patients from January 2016 to November 2020. Inclusion: ≥ 18 years old and > 72 hours of renally adjusted high-dose TMP-SMX defined as ≥ 5 mg/kg/day of TMP. Exclusion: prophylaxis. Endpoints during treatment: hyponatremia with sodium < 135 mmol/L, hyperkalemia with potassium > 5 mmol/L, serum creatinine increase of ≥ 0.3 mg/dL or 1.5-1.9 times from baseline, and fluid overload on physical exam. Descriptive and bivariate statistics were performed.ResultsEach group included 50 patients (Table 1). Intensive care unit patients comprised 82% IV TMP-SMX compared to 32% PO. Most common infection: respiratory tract 86% IV and 68.1% PO. Most common organisms were Stenotrophomonas maltophilia (52% IV and 18% PO) and Pneumocystis jiroveci (16.3% IV and 62% PO). Median (IQR) days of inpatient therapy: 6 (5-7.5) PO vs. 7.5 (6-11.3) IV. Median (IQR) days of total duration: 9 (6-21.5) PO vs. 12 (7.8-14) IV (p=0.93). IV group: 88% of patients received >1 liter of D5W daily. Median (IQR) liters of D5W daily was 1 (1-1.5). 56% had a diuretic added, and 38% had a diuretic dose increase. Majority of patients (78%) on IV were taking other oral medications. 100% patients experienced any adverse event with IV vs. 70% with PO (unAdjOR 2.43; 95% CI 1.89-3.13). Most common ADE in both groups: hyponatremia, hyperkalemia, and elevated creatinine. Hyponatremia: 92% with IV and 32% with PO (unAdjOR 24.44; 95% CI 7.50-79.68). Edema on physical exam, an ADE specific to IV TMP-SMX, was the third most common side effect in the IV group. Relative changes from baseline in sodium, potassium, and creatinine from those who experienced hyponatremia, hyperkalemia and elevated creatinine were listed in Table 2.Table 1. Baseline and Clinical Characteristics Table 2. Adverse Effects ConclusionPatients on IV TMP-SMX therapy were more likely to experience an ADE compared to PO, likely driven by the high volume of free water. Most patients on IV TMP-SMX were on other PO medications, suggesting a missed stewardship opportunity for IV to PO conversion to reduce patient harm.Disclosures Susan L. Davis, PharmD, Nothing to disclose Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

1491. Standard- vs. High-dose Trimethoprim-Sulfamethoxazole for Stenotrophomonas maltophilia pneumonia

Background Stenotrophomonas maltophilia is a multidrug-resistant pathogen known to cause pneumonia with associated mortality rates up to 44%.1,2 Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice based on available clinical evidence and excellent in-vitro susceptibility rates.3 High-dose TMP-SMX strategies recommend between 15-20mg/kg/day of the TMP component, however this has been associated with increased adverse drug events (ADE).4,5 The optimal dosing strategy remains unclear and it is unknown whether lower doses of TMP-SMX would achieve similar outcomes.MethodsPatients with positive respiratory cultures for S. maltophilia who received at least 72 hours of TMP-SMX therapy for hospital-acquired or ventilator-associated pneumonia from January 2010 to March 2020 were included. Doses were categorized as standard-dose (SD) TMP-SMX (< 15 mg/kg/day TMP) or high-dose (HD) TMP-SMX (≥ 15 mg/kg/day TMP) after adjusting for renal function. The primary outcome was clinical success, defined as the composite of resolution of signs/symptoms of pneumonia, in-hospital survival, and no escalation of care. Secondary outcomes included hospital length of stay (LOS), 30-day mortality, 30-day readmission, and ADE.ResultsOf the 44 patients meeting inclusion criteria for the study, 27 received SD and 17 received HD TMP-SMX therapy. Patients received 12 mg/kg/day (IQR 11-14) and 16 mg/kg/day (IQR 16-19) in the SD and HD groups, respectively. There was no difference in clinical success between the SD and HD group (41% vs 59%, p=0.24). Secondary outcomes were similar between both groups except for 30-day hospital readmission; the SD group had significantly lower readmission rates (6% vs 69%, p < 0.01). Rates of adverse events were not statistically different between the two groups.ConclusionThis study provides evidence that SD TMP-SMX may achieve similar clinical efficacy to HD TMP-SMX. We found no significant difference in clinical success, LOS, 30-day mortality, or adverse events between groups. Although HD TMP-SMX is the current recommendation for S. maltophilia infections, concerns about tolerability and adverse effects suggest that further clinical and pharmacodynamic research is needed.Disclosures All Authors: No reported disclosures

Hypouricemia: what the practicing rheumatologist should know about this condition.

We presented an update in the field of hypouricemia, which is defined as a serum urate concentration of < 2mg/dL (119μmol/L), for the practicing rheumatologist, who usually is the consulting physician in cases of disorders of urate metabolism. We performed a narrative review through a literature search for original and review articles in the field of human hypouricemia published between January 1950 and July 2018. We divided the etiology of hypouricemia into two main categories: those associated with a decrease in urate production and those promoting the elimination of urate via the kidneys. The most common conditions associated with these categories are discussed. Furthermore, the etiology of hypouricemia may be associated with certain medications prescribed by the practicing rheumatologists, such as the following: urate-lowering drugs (allopurinol and febuxostat); recombinant uricase (pegloticase); uricosuric agents (probenecid, benzbromarone); urate transporter URAT1 inhibitor (lesinurad); angiotensin II receptor blocker (losartan); fenofibrate; high-dose trimethoprim-sulfamethoxazole; some NSAID; and high-dose salicylate therapy. The rheumatologist is considered an expert in the metabolism of urate and its associated pathological conditions. Therefore, specialists must recognize hypouricemia as a biomarker of various pathological and potentially harmful conditions, highlighting the importance of conducting a deeper clinical investigation to reach a more accurate diagnosis and treatment.

Oral eradication therapy for melioidosis: Important but not without risks

ObjectivesThe purpose of this study was to quantify the adverse effects from oral eradication therapy for melioidosis, which is usually with high dose trimethoprim-sulfamethoxazole for 3–6 months. MethodsThis retrospective cohort study reviewed side effects from oral eradication therapy in patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia’s Northern Territory between 1st October 2012 and 1st January 2017. Results234 patients presented for the first time with culture-confirmed melioidosis. Of these, 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital. Of the remaining 212 patients, 203 (95.8%) were initially prescribed trimethoprim-sulfamethoxazole as oral eradication therapy, 6 (2.8%) were prescribed doxycycline and 3 (1.4%) had no eradication therapy. Of the 203 prescribed trimethoprim-sulfamethoxazole, 61 (30.0%) experienced adverse effects, which necessitated a cessation, a change in antibiotic or reduction in dose. ConclusionsIn patients treated for melioidosis in northern Australia there are high rates of adverse effects from oral trimethoprim-sulfamethoxazole, frequently necessitating a change in therapy or a reduction in dose. Given the side effects and low rates of oral therapy completion in our region we emphasise the importance of the prior often prolonged intensive phase intravenous therapy and using weight based trimethoprim-sulfamethoxazole dosing for eradication therapy.

175 Dose Dependent Hyponatremia Associated with High-Dose Trimethoprimsulfamethoxazole for Treatment of Disseminated Nocardia Infection After Kidney Transplantation

175 Dose Dependent Hyponatremia Associated with High-Dose Trimethoprimsulfamethoxazole for Treatment of Disseminated Nocardia Infection After Kidney Transplantation

An unexpected cause of hyponatremia in a cancer patient: Trimethoprim-sulfamethoxazole

Abstract: Background Hyponatremia is one of the most common electrolyte abnormalities seen in hospitalized patients. In cancer patients, it's generally related to syndrome of inappropriate ADH secretion (SIADH). Case Report Here, we report a breast cancer patient with hyponatremia related to high dose trimethoprim-sulfamethoxazole use for pneumonitis cariini pneumonia. Conclusion It is important to be aware that all hyponatremias are not related to SIADH in cancer patients. For proper treatment strategies, a proper differential diagnosis is needed.

Are Lower Trimethoprim–Sulfamethoxazole Doses Effective for Pneumocystis Pneumonia?

Current guidelines recommend treating Pneumocystis jirovecii pneumonia (PCP) with high-dose trimethoprim–sulfamethoxazole (TMP–SMX; TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day in 4 divided doses) for 2 to 3 weeks. Given the high frequency of adverse events associated with this regimen — including renal insufficiency, electrolyte disorders, and liver toxicity — researchers in the Netherlands retrospectively examined the efficacy of a TMP–SMX dose step-down …

Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study.

BackgroundThe recommended treatment of Pneumocystis jirovecii pneumonia (PCP) is high-dose trimethoprim–sulfamethoxazole (TMP–SMX) in an equivalent of TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day for 2 or 3 weeks. High rates of adverse events are reported with this dose, which raises the question if lower doses are possible.MethodsAll adult patients diagnosed with PCP in various immune dysfunctions and treated with TMP–SMX between January 1, 2003 and July 1, 2013 in a tertiary university hospital were included. Per institutional protocol, patients initiated treatment on intermediate-dose TMP–SMX (TMP 10–15 mg/kg/day) and could be stepped down to low-dose TMP–SMX (TMP 4–6 mg/kg/day) during treatment. Clinical variables at presentation, relapse rate and mortality rates were compared between intermediate- and step-down treatment groups by uni- and multivariate analyses.ResultsA total of 104 patients were included. Twenty-four patients (23 %) were switched to low-dose TMP–SMX after a median of 4.5 days (IQR 2.8–7.0 days). One relapse (4 %) occurred in the step-down group versus none in the intermediate-dose group. The overall 30-day mortality was 13 %. There was 1 death in the step-down group (4 %) compared to 13 deaths (16 %) in the intermediate-dose group.ConclusionsWe observed high cure rates of PCP by treatment with intermediate-dose TMP–SMX. In addition, a step-down strategy to low-dose TMP–SMX during treatment in selected patients appears to be safe and does not compromise the outcome of treatment.

Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial

Objective To show non-inferiority of trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant Staphylococcus aureus (MRSA).Design Parallel, open label, randomised controlled trial.Setting Four acute...

Nocardia brasiliensis Infection Mimicking Juvenile Idiopathic Arthritis in a 4-Year-Old Girl

Nocardia are ubiquitous environmental saprophytes that cause pneumonia and disseminated disease in immunocompromised patients. They can also cause localized cutaneous and soft tissue infections in healthy people after direct percutaneous inoculation. Nocardia arthritis is rare in both forms of the disease. Here we present the first published case of a child with septic arthritis caused by N brasiliensis. Importantly, this otherwise well 4-year-old girl had no known history of trauma but presented with transient cutaneous lesions and a 6-week history of arthritis involving the right fourth digit proximal interphalangeal joint without accompanying fever or raised systemic inflammatory markers. She received a diagnosis of juvenile idiopathic arthritis and underwent antiinflammatory and immunosuppressant therapy. After 2 months she developed frank septic arthritis, which necessitated a surgical joint washout, from which an intraoperative swab grew N brasiliensis. The patient received 6 months of high-dose trimethoprim-sulfamethoxazole and remains well more than 4 years after treatment. This unusual case highlights the importance of considering an indolent infection from slow-growing organisms, including Nocardia, when diagnosing the oligoarthritis subtype of juvenile idiopathic arthritis. This is especially relevant when a single joint is involved and response to antiinflammatory therapy is suboptimal because antiinflammatory agents may mask evolving signs of infection.

An Evaluation of Hyperkalemia and Serum Creatinine Elevation Associated With Different Dosage Levels of Outpatient Trimethoprim-Sulfamethoxazole With and Without Concomitant Medications

Adverse events associated with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) for outpatient infections, particularly those likely caused by community-acquired methicillin-resistant Staphylococcus aureus, have not been adequately characterized. Describe hyperkalemia and acute renal injury associated with high-dose TMP-SMX. An electronic medical record database retrospective study was conducted of outpatients receiving high-dose or low-dose TMP-SMX, comparing the incidences of hyperkalemia and acute renal injury. Of 6162 patients, more developed hyperkalemia (3.06% vs 1.05%, P < .0001) or acute renal injury (1.99% vs 0.700%, P = .0001) in the high-dose TMP-SMX group. Variables independently associated with hyperkalemia included age >58 years (odds ratio [OR] = 3.44; 95% CI = 1.86-7.0; P < .0001), concomitant receipt of an NSAID (OR = 1.71; 95% CI = 1.02-2.79; P = .044) or an ACE inhibitor (OR = 3.27; 95% CI = 2.06-5.14; P < .0001), high-dose TMP-SMX prescribed (OR = 2.92; 95% CI = 1.85-4.60; P < .0001), and baseline elevated serum creatinine (OR = 45.1; 95% CI = 21.7-93.2; P < .0001). Variables independently associated with acute renal injury included concomitant receipt of an ACE inhibitor (OR = 2.36; 95% CI = 1.01-5.24; P = .048) or a potassium supplement (OR = 4.10; 95% CI = 1.45-10.1; P = .010), high-dose TMP-SMX prescribed (OR = 3.70; 95% CI = 1.70-8.12; P = .0012), and baseline elevated serum creatinine (OR = 2110; 95% CI = 724-7980; P < .0001). Serum creatinine and potassium concentrations should be monitored in outpatients receiving high-dose TMP-SMX.

A Comparison of Adverse Drug Reactions Between High- and Standard- Dose Trimethoprim-Sulfamethoxazole in the Ambulatory Setting

High-dose trimethoprim-sulfamethoxazole (TMP-SMX) for the empiric treatment of community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infections has been evaluated for efficacy, but characterization of adverse reactions is lacking. To describe adverse reactions associated with high-dose TMP-SMX therapy, a retrospective medical record review of outpatients receiving TMP-SMX was conducted. Each episode (case) of a patient receiving high-dose TMP-SMX (at least 4 double-strength tablets per day) was matched by next closest prescription number with a patient (control) receiving standard-dose TMP-SMX. 982 cases were reviewed; 491 in each arm. At least one adverse drug reaction (ADR) occurred in 9.1% of patients. There was a significant difference in the incidence for any ADR between high-dose and standard-dose groups (13.0% vs 5.09%, respectively; p<0.0001). More patients taking high-dose TMP-SMX developed hyperkalemia (3.46% vs 0.81%, p=0.0066), acute renal injury (3.67% vs 1.63%, p=0.044), and rash (1.83% vs 0.20%, p=0.021). Patients receiving high-dose TMP-SMX had significantly higher rates of electrolyte abnormality ADR (5.09% vs 1.63%, p=0.0021), gastrointestinal ADR (5.30% vs 2.24%, p=0.011), renal ADR (3.67% vs 1.63%, p=0.044), central nervous system ADR (2.65% vs 0.81%, p=0.047), and hypersensitivity (2.24% vs 0.41%, p=0.022). Concomitant receipt of an angiotensin-converting enzyme (ACE) inhibitor was a univariate variable associated with hyperkalemia, and advanced age and receipt of high-dose TMP-SMX were independent variables. ADRs such as hyperkalemia are more likely to be associated with the use of high-dose TMP-SMX in the ambulatory setting. Clinicians should use caution when initiating high-dose TMP-SMX and consider laboratory monitoring in patients of advanced age or those receiving concomitant ACE inhibitor therapy.

Diagnosis and Antimicrobial Therapy of Lung Infiltrates in Febrile Neutropenic Cancer Patients

Pulmonary infiltrates develop in up to 25% of febrile neutropenic patients and are frequently refractory to broad-spectrum antibacterial therapy. Etiologically, Aspergillus spp., Pneumocystis jiroveci, multi-resistant Gram-negative rods as well as mycobacteria and respiratory viruses may be involved. Taking into account the predominant role of fungal pathogens, typically without microbiological proof, prompt addition of mold-active systemic antifungal therapy improves clinical outcome, while other microorganisms should typically be targeted based upon microbiological test results only. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their etiological relevance for pulmonary infiltrates. Non-culture based diagnostic procedures to detect circulating antigens such as galactomannan or 1,3-beta-D-glucan, or PCR techniques to amplify DNA from blood, bronchoalveolar lavage or tissue specimens, may facilitate the diagnosis. For pre-emptive antifungal treatment, voriconazole or liposomal amphotericin B are preferred. Antifungal treatment should be continued for at least 14days before non-response and treatment modification are considered. Primary choice for treatment of Pneumocystis pneumonia remains high-dose trimethoprim-sulfamethoxazole, while cytomegalovirus pneumonia is treated with ganciclovir in the majority of patients affected.

Iatrogenic, sulfonamide‐induced hypothyroid crisis in a Labrador Retriever

This case report describes a sulfonamide-induced hypothyroid crisis in a 4-year-old Labrador Retriever bitch. Empirical therapy with high-dose trimethoprim-sulfamethoxazole for 10 days produced signs of weakness, ataxia and mental depression and the clinicopathological results supported hypothyroid-induced central nervous system depression. Short-term levothyroxine sodium therapy led to complete resolution of all clinical signs and follow-up thyroid hormone assays ruled out underlying thyroid pathology. This case report is the first to highlight this potentially life-threatening manifestation of sulfonamide-induced hypothyroidism. Sulfonamide combinations are widely used antimicrobials in veterinary medicine and early recognition of this syndrome is critical.

Acute Respiratory Infections in a Recently Arrived Traveler to Your Part of the World*

Many acute infectious pulmonary diseases have incubation periods that are long enough for travelers to have symptoms after returning home to a health-care system that is not familiar with “foreign” infections. Respiratory infections have a relatively limited repertoire of clinical manifestations, so that there is often nothing characteristic enough about a specific infection to make the diagnosis obvious. Thus, the pathway to the diagnosis of infections that are not endemic in a region relies heavily on taking a thorough history of both itinerary and of specific exposures. One important caveat is that on occasion, the history of a recent trip creates an element of “tunnel vision” in the evaluating health-care provider. It is tempting to relate a person's problem to that recent trip; however, when evaluating recent returnees, it is always important to remember that the travel may have nothing to do with the patient's presentation. Recent travel may add diagnostic considerations to the list of possibilities, but an astute clinician must not disregard the possibility that the patient's illness has nothing to do with the recent trip.

Efficacy of Caspofungin Addition to Trimethoprim-Sulfamethoxazole Treatment for Severe Pneumocystis Pneumonia in Solid Organ Transplant Recipients

Pneumocystis jiroveci pneumonia may be a life-threatening opportunistic infection in immunosuppressed solid organ transplant recipients. Despite effective treatment with high-dose trimethoprim-sulfamethoxazole and steroids, morbidity is often severe and lethality remains high. New therapeutic approaches are therefore warranted. Caspofungin, a beta-1,3-glucan synthesis inhibitor, has shown activity against the cyst forms of P. jiroveci in experimental animal models. We here report our preliminary clinical experience with caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen. Four solid organ transplant patients with severe hypoxemic P. jiroveci pneumonia were treated with the combination of trimethoprim-sulfametoxazole and caspofungin. In two cases, caspofungin was added as salvage treatment due to failure of trimethoprim-sulfametoxazole monotherapy. In these four patients, the use of caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen led to a rapid improvement and a complete cure of pneumonia. No side effects or drug interactions were observed. This preliminary clinical experience suggests that the addition of caspofungin to trimethoprim-sulfamethoxazole, which is active against trophic forms, may provide a synergistic activity against P. jiroveci by fully inhibiting the organism life cycle.