Administration Of Trimethoprim-sulfamethoxazole Research Articles

Factors affecting the course and prognosis of implant-associated infection caused by <i>Klebsiella</i> spp.

Background. The outcome of complex treatment of implant-associated infection (IAI) depends on various factors, but one of the most important is the etiology of the inflammatory process. Treatment of orthopedic infection caused by Gram-negative microorganisms in general and representatives of the family Enterobacteriaceae in particular causes many difficulties, one of which is the rapid growth of antibiotic resistance. Aim of the study — to evaluate the factors affecting the course and prognosis of implant-associated infection caused by Klebsiella spp. Methods. We performed a retrospective analysis of case histories of 85 patients who underwent treatment of IAI caused by Klebsiella spp. in the clinical departments of the center from January 1, 2017 to December 31, 2021. According to the results of the telephone survey, the patients were divided into 2 main groups depending on the outcome of the 2-year follow-up period determined in accordance with the Delphi criteria. Results. It was found that the prognosis was significantly worsened by the number of sanitizing surgical interventions in the anamnesis (p = 0.022), the need for sanitizing intervention in the early postoperative period (p0.001) and the presence of Klebsiella spp. growth in postoperative culture tests (p = 0.002), hypoalbuminemia on 7-14 days after the surgery (p = 0.008). The administration of trimethoprim-sulfamethoxazole for the outpatient treament stage significantly improved the outcome (p = 0.038), which is most likely due to a high proportion of polymicrobial associations — 69.5%. Conclusions. There is a statistically significant direct relationship between the probability of an unfavorable treatment outcome of patients with IAI caused by Klebsiella spp. and the number of sanitizing surgical interventions in the anamnesis, low serum albumin (g/l) on 7-14 days after the operation, revision intervention in the early postoperative period, positive growth of Klebsiella spp. in postoperative culture tests. The probability of a favorable outcome was increased by the prescription of trimethoprim-sulfamethoxazole for oral administration at the outpatient stage.

Clinical Characteristics and Epidemiological Analysis of Pneumocystis Jirovecii Pneumonia Infection in Kidney Transplant Patients with Trimethoprim-Sulfamethoxazole Dose Reduction Prophylaxis Strategy.

The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection. This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3-51 months. Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50±7.11 months. Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.

Mild Pulmonary Nocardiosis Caused by Nocardia terpenica in an Immunocompetent Patient: A Case Report.

A 53-year-old immunocompetent man was admitted to our hospital because of paroxysmal cough with a low fever for more than 5 months. On admission, chest computed tomography showed multiple plaques and nodules, some with small central cavities, in both lungs and cystic and columnar bronchiectasis of the right middle bronchus. Treatment with various antibiotics was ineffective. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid showed Nocardia terpenica, and this organism was cultured from bronchoalveolar lavage fluid, resulting in a diagnosis of pulmonary nocardiosis. After administration of trimethoprim-sulfamethoxazole for 5 weeks, chest computed tomography showed a significant reduction in the lung lesions that had been detected on admission. Immunosuppressed patients are particularly prone to nocardiosis infection, which is usually severe. N. terpenica has rarely been detected in clinical samples, and its characteristics require further study with the accumulation of more clinical cases.

Anti-tumor activity of trimethoprim-sulfamethoxazole against melanoma skin cancer through triggering allergic reaction and promoting immunity

The anti-cancer impact of an allergic reaction is strongly linked to immunity enhancement. Trimethoprim-sulfamethoxazole (TMP-SMX), an antibiotic, has potential immunomodulatory effects, but has side effects such as allergies. Thus far, the effects and underlying mechanisms of TMP-SMX in melanoma have not been clarified. This study examined the potential roles of TMP-SMX in melanoma skin cancer using an immunodeficient mouse model. TMP-SMX significantly improved the survival rate and reduced the tumor weight and growth and vascular endothelial growth factor levels in melanoma skin cancer of immunodeficient mice. In the forced swimming test, TMP-SMX significantly reduced immobility time compared to the melanoma skin cancer of immunodeficient mice, indicating improved immunity. TMP-SMX significantly increased infiltration of mast cells and release of allergy-related mediators (IgE, histamine, interleukin (IL)-4, IL-5, IL-13, and IL-33) and immune-enhancing mediators (tumor necrosis factor-α, IL-2, IL-6, and IL-12). In addition, the administration of TMP-SMX significantly increased the caspase-3, 8, and 9 activities. Furthermore, mice given TMP-SMX showed no adverse reactions according to the blood biochemical parameters. TMP-SMX significantly inhibits the growth of melanoma skin cancer by triggering an allergic reaction and promotingimmunity. Hence, we propose that TMP-SMX may be used as an immune booster in cancer chemotherapy.

Colonic cryptococcosis presenting with chronic diarrhea in a person with advanced human immunodeficiency virus disease: a case report

Cryptococcus neoformans infection usually occurs in patients with advanced human immunodeficiency virus (HIV) infection or with a CD4 T lymphocyte count of <100 cells/μL. Pulmonary and central nervous system infections are the most frequently encountered forms of cryptococcosis; however, colonic cryptococcosis is uncommon. We describe the case of a 41-year-old antiretroviral-naïve man with HIV infection diagnosed eight years prior and intermittent diarrhea for 4 months who presented to the emergency department with a 1-day history of low-grade fever and confusion. Brain magnetic resonance imaging and cerebrospinal fluid analysis revealed normal results; however, he was diagnosed with Pneumocystis jirovecii pneumonia based on chest computed tomography and bronchoalveolar lavage analysis. Trimethoprim-sulfamethoxazole administration was initiated followed by antiretroviral treatment. Although his condition gradually improved, he developed fever and abdominal discomfort, and the diarrhea worsened. Endoscopy revealed a small ulcer in the distal transverse colon. Histopathological examination of a colon tissue sample revealed cryptococcal infection. He improved substantially during liposomal amphotericin B and fluconazole treatment. We encountered a rare case of colonic cryptococcosis that caused chronic diarrhea in a patient with advanced HIV infection. Colonic cryptococcosis should be considered when patients with acquired immune deficiency syndrome present with gastrointestinal symptoms.

532 Cross-Reactivity Between Topical and Systemic Sulfa Antibiotics

IntroductionSilver sulfadiazine cream 1% is a sulfa derivative topical antimicrobial commonly used in burn care, in part due to its wide spectrum of activity, particularly against Pseudomonas aeruginosa. Contact dermatitis due to sulfadiazine component is a known but rare complication of silver sulfadiazine. In contrast, systemic sulfonamide antimicrobials are a commonly reported allergy and have been implicated in multiple hypersensitivity reactions. Some authors recommend avoidance of all sulfonamide antimicrobials regardless of route of administration for a patient with a known allergy to a sulfonamide antimicrobial due to structural similarities between all drugs in the class, resulting in a high risk of cross-reactivity. Clinical reports are lacking, however, and the few reports that do exist implicate silver as the culprit rather than the sulfadiazine component. Therefore, while the theoretical risk of reactivity to a topical application of sulfadiazine exists, there is no data to support this in practice.MethodsA retrospective review of 42 patients with a sulfa allergy who were admitted to the burn unit of an academic medical center between June 2016 and June 2021 were reviewed. Inclusion criteria were age > 18, burn requiring admission, sulfa allergy, and receiving topical sulfa antimicrobial therapy. Data on the reported allergen, reaction, and any adverse reaction from the use of topical sulfa agents were recorded.ResultsForty-two patients were identified. Of these, 32 (76%) reported a non-specific “sulfa” allergy, while 10 (24%) reported a specific allergy to trimethoprim-sulfamethoxazole. The reactions were reported as unknown (20, 48%), rash (9, 21%), hives (6, 14%), gastrointestinal (4, 9%), or other (3, 7%). One patient had a history of respiratory distress with trimethoprim-sulfamethoxazole administration. All 42 patients received treatment with topical silver sulfadiazine and 10 also were treated with topical mafenide acetate solution. There were no reported adverse events and no patients discontinued therapy. Two patients were identified with no previous sulfa allergy but who discontinued topical silver sulfadiazine due to burning sensation, a rare but previously reported side effect of this medication.ConclusionsSilver sulfadiazine remains one of the most commonly used topical antimicrobials in burn care due to its broad spectrum of activity, low cost, and ease of use. Adverse reactions to topical silver sulfadiazine and mafenide acetate are rare, even in those with reported sulfa allergies. Topical sulfa anti-microbials can likely be used safely in most patients with allergies to systemic sulfa antibiotics, and the rate of cross-reactivity appears to be low. A test patch is recommended prior to application over a large area.

Primary Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients Receiving Rituximab

Although previous studies suggested that rituximab increases the risk of Pneumocystis jirovecii pneumonia (PJP), it is uncertain whether its primary prophylaxis for PJP is justified. Does the benefit of primary prophylaxis for PJP in patients receiving rituximab treatment outweigh the potential risk of the prophylaxis? This retrospective study included 3,524 patients (hematologic diseases, 2,500; rheumatic diseases, 559; pre/post-solid organ transplantation, 465) first exposed to rituximab between 2002 and 2018 in a tertiary referral center in South Korea. Patients were classified into a control group (n= 2,523) and a prophylaxis group (n= 1,001) according to the administration of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) during the first 28days after the start of rituximab (intention-to-treat analysis). In addition, exposure to TMP-SMX was examined as a time-varying variable (time-varying analysis). The primary outcome was the prophylactic effect of TMP-SMX on the 1-year incidence of PJP. Inverse probability of treatment weights was applied to minimize the baseline imbalance. The secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX. Over 2,759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted subdistribution hazard ratio, 0.20 [95%CI, 0.10-0.42]) than the control group. This result was consistent with the results of time-varying analysis, in which only one PJP infection occurred during TMP-SMX administration (adjusted subdistribution hazard ratio, 0.01 [0.003-0.16]). The incidence of ADRs related to TMP-SMX was 18.1 (14.6-22.2)/100 person-years, and most were of mild to moderate severity. On the basis of 10 severe ADRs, the number needed to harm was 101 (61.9-261.1), whereas the number needed to prevent one PJP infection was 32 (24.8-39.4). TMP-SMX prophylaxis significantly reduces PJP incidence with a tolerable safety profile in patients receiving rituximab treatment.

Stage-Specific Oligonucleotide Primers for the Diagnosis of Toxoplasmosis Among Iranian Pediatric Heart Transplant Recipients; Evaluation of Cotrimoxazole as a Preventive Therapy

Background: Toxoplasmosis is an opportunistic infection that affects solid organ transplant (SOT) recipients. The parasite transmission may be occurred from a Toxoplasma-seropositive donor to a Toxoplasma-seronegative recipient by organ transplantation. Objectives: In this study, a nested PCR was carried out using different primers targeting the B1, SAG4, and MAG1 genes to assess Toxoplasma infection in pediatric heart transplantation at Shahid Rajaei Heart Center in Tehran. Methods: Blood samples were collected from 46 pediatric heart transplant patients aged 1 - 17 years referring to Rajaei Cardiovascular Medical and Research Center from 2018 - 2019. All patients were on oral administration of Trimethoprim-sulfamethoxazole (cotrimoxazole). Blood samples were collected, and peripheral blood mononuclear cell (PBMC) isolation using the Ficoll gradient method was performed. DNA was extracted from PBMC, and nested PCR was carried out. Serologic tests were performed using ELISA to determine IgG and IgM anti - Toxoplasma gondii antibodies. Results: The results of serologic tests showed that all 46 patients had negative anti-T. gondii IgM antibody. Furthermore, 6 (13.05%) and 3 (6.5 %) out of the 46 patients were positive for IgG T. gondii antibody before and after transplantation, respectively. All 46 patients were evaluated using PCR using B1, MAG-1, and SAG-4 genes, and PCR results were negative. Conclusions: In general, due to the negative results of Toxoplasma with PCR using B1 and bradyzoite-specific genes (SAG-4 and MAG-1), it is possible that the results obtained in this study are because of prophylaxis with cotrimoxazole.

Safety and efficacy evaluation of low-dose trimethoprim-sulfamethoxazole for prophylaxis of Pneumocystis pneumonia in HIV uninfected patients undergoing hemodialysis: a retrospective observational study

BackgroundPneumocystis pneumonia (PCP) is a potentially life-threatening infection. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered as the first regimen for PCP prophylaxis according to several guidelines. The recommended prophylactic dose of TMP-SMX has been determined based on patients with normal renal function, but the appropriate dosage for patients undergoing hemodialysis is unknown. The aim of this study was to investigate the efficacy and safety of low-dose TMP-SMX in patients undergoing hemodialysis.MethodsHIV-uninfected adult patients who were undergoing hemodialysis and administered TMP-SMX for PCP prophylaxis, were included, and divided into standard-dose (≥6 single strength (SS, TMP-SMX 80 mg/400 mg tablets/week) and low-dose groups (< 6 SS tablets/week). The endpoints were cumulative incidence of PCP and cumulative discontinuation rate of TMP-SMX due to adverse events. For comparison of the groups, we employed the chi-squared test for categorical variables and the Mann-Whitney U test for continuous variables. Risk factors for the endpoints were evaluated using the Cox Fine and Gray method.ResultsThe median age of the 81 patients included in the study was 67 years (IQR: 60–76 years), and 52 patients (64.2%) were men. No patients in either group developed PCP during the observation period. The yearly cumulative incidence of discontinuation was 12.1% (95% confidence interval [CI]: 0.027–0.29) in the low-dose group and 35.6% (95% CI: 0.20–0.52) in the standard-dose group (P = 0.019). The adjusted hazard ratio of the low-dose group compared to standard-dose group was 0.18 (95% CI: 0.04–0.86, P = 0.032).ConclusionsNone of the study patients developed PCP, and the cumulative discontinuation rate of TMP-SMX due to adverse events was significantly lower in the low-dose group compared to that in the standard-dose group (P = 0.032). These results indicate that low-dose TMP-SMX is an appropriate regimen to maintain a balance between PCP prophylaxis and prevention of adverse events due to TMP-SMX administration. These findings can guide health care professionals to determine TMP-SMX dosage when considering PCP prophylaxis for patients undergoing hemodialysis.

Pneumocystis Pneumonia: Immunity, Vaccines, and Treatments.

For individuals who are immunocompromised, the opportunistic fungal pathogen Pneumocystis jirovecii is capable of causing life-threatening pneumonia as the causative agent of Pneumocystis pneumonia (PCP). PCP remains an acquired immunodeficiency disease (AIDS)-defining illness in the era of antiretroviral therapy. In addition, a rise in non-human immunodeficiency virus (HIV)-associated PCP has been observed due to increased usage of immunosuppressive and immunomodulating therapies. With the persistence of HIV-related PCP cases and associated morbidity and mortality, as well as difficult to diagnose non-HIV-related PCP cases, an improvement over current treatment and prevention standards is warranted. Current therapeutic strategies have primarily focused on the administration of trimethoprim-sulfamethoxazole, which is effective at disease prevention. However, current treatments are inadequate for treatment of PCP and prevention of PCP-related death, as evidenced by consistently high mortality rates for those hospitalized with PCP. There are no vaccines in clinical trials for the prevention of PCP, and significant obstacles exist that have slowed development, including host range specificity, and the inability to culture Pneumocystis spp. in vitro. In this review, we overview the immune response to Pneumocystis spp., and discuss current progress on novel vaccines and therapies currently in the preclinical and clinical pipeline.

Test-dose as a De-labeling Tool in Patients with Self-reported Sulfonamide Allergy: A Quality Improvement Project

We aimed to assess an intervention implemented in our Allergy Clinic to de-label non-HIV patients with self-reported sulfonamide allergy utilizing a previously published test-dose challenge of trimethoprim-sulfamethoxazole (TMP-SMX). A pre-/post-intervention, quality improvement design in patients with self-reported non-severe delayed, immediate or unknown reaction to TMP-SMX. We compared the effectiveness of a one-to-two step test-dose versus a 6-step desensitization of TMP-SMX. The main outcome measure was the rate of success for desensitization versus test-dose. Patients were contacted in the test-dose group via phone to evaluate safety of further TMP-SMX administration. Cost for each procedure was estimated based on current Medicare standards. A total of 52 patients underwent sulfonamide desensitization in the two-year (2017-2018) pre-intervention period and were compared with 53 patients who underwent test-dose administration of TMP-SMX in the two-year (2019-2020) post-intervention period. In both periods, most patients were female (87% versus 75%), white (85% versus 96%), and over 60 years of age (60% versus 58%). In the test-dose group, 51% underwent a two-step test-dose. The success rates of desensitization and test-dose were similar (94% versus 90%; P = .72). In the test-dose group, none of the 37 patients who received a course TMP-SMX post de-labeling reported an adverse drug reaction. The estimated post-intervention cost reduction was $13,217. The implementation of a validated protocol for graded administration of TMP-SMX revealed similar success rates than desensitization, with a decrease cost, and without an increase of adverse events.

Determinants of Malaria Protective Immunity in Mice Immunized with Live Sporozoites during Trimethoprim-Sulfamethoxazole Prophylaxis.

.HIV and malaria geographically overlap. Trimethoprim–sulfamethoxazole (TMP-SMX) is a drug widely used in HIV-exposed uninfected and infected children in malaria-endemic areas, and is known to have antimalarial effects. Further study in terms of antimalarial impact and effect on development of malaria-specific immunity is therefore essential. Using rodent malaria models, we previously showed that repeated Plasmodium exposure during TMP-SMX administration, or chemoprophylaxis vaccination (CVac), induces CD8 T-cell–dependent preerythrocytic immunity. However, humoral immune responses have been shown to be important in models of preerythrocytic immunity. Herein, we demonstrate that antibody-mediated responses contribute to protective immunity induced by CVac immune sera using TMP-SMX in models of homologous, but not heterologous, parasite species. Clinical studies must account for potential anti-Plasmodium antibody induced during TMP-SMX prophylaxis.

Diagnostic value of real-time PCR of brain mass lesion in HIV-associated toxoplasmic encephalitis: a case series

BackgroundToxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE.MethodsA total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service.ResultsThere were 8 male and 1 female patients; their age ranged from 26 to 56 years-old. The main symptom was intracranial hypertension (6/9). Six patients presented multiple brain lesions, which were mainly located in the supratentorial area (7/9). CD4+ count ranged from 11 to 159 cells/μl (median 92 cells/μl), and serological HIV viral load 0–989190 copies/ml (median 192836 copies/ml). IgG and IgM against serum TG were positive in 7 and 1 patients, respectively. Moreover, regarding CSF, IgG against TG was positive in 3 patients, while all patients were negative for IgM. The neuroimaging features on MRI showed no specificity. Four patients were diagnosed with TE by histopathological findings. After receiving anti-Toxoplasma therapy, 8 (8/9) patients improved clinically to a considerable extent.ConclusionsThe application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.Graphical

P0748CLINICAL OUTCOMES OF JAPANESE ANTI-MYELOPEROXIDASE ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-RELATED RAPIDLY PROGRESSIVE GLOMERULAR NEPHRITIS

Abstract Background and Aims Anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-related nephritis constitutes 60% of rapidly progressive glomerular nephritis (RPGN). In 2014, Japanese Society of Nephrology (JSN) created RPGN clinical guidelines for Japanese MPO-ANCA-related RPGN patients, and proposed the clinical grading system for predicting their prognosis, which took into consideration factors such as age, renal function, lung involvement, and serum CRP (Yoshihiro Arimura et al. Clin Exp Nephrol. 2016). However, evidence regarding clinical outcomes is still limited. In the study reported here, we conducted a single-center retrospective study to evaluate the outcomes of MPO-ANCA-related RPGN patients and to establish an efficacy of RPGN guidelines of JSN. Method We retrospectively investigated 54 patients (female, n=32; average age ± 13.0 years) with MPO-ANCA-related nephritis. The patients were admitted to Fukuoka University Hospital between 2009 and 2018. Their clinical grade determined by JSN guideline and method of treatment were retrospectively evaluated for prediction of survival, as well as laboratory data and clinical features. Results 12 patients (22.2 %) has deceased during a median observation period of 17.1 months. 7 patients are died of infectious disease (Bacterial pneumonia 4, Sepsis 2, pulmonary aspergillosis 1), and 10 patients died within 1 year. Median estimated glomerular filtration rate (eGFR) was 15.5 mL/min/1.73m2 at admission. 14 patients (25.9%) presented with end-stage renal disease (ESRD) during the observation period, 8 of them were died. The distribution of clinical grade of JSN guideline was grade I for 10, II for 27, III for 10 and IV for 7. (grade IV is the most severe) Patients with high clinical grade showed significantly high mortality (Log Rank test, p&amp;lt;0.05; figure 1). Multivariate Cox proportional hazards model analysis revealed that high clinical grade was a significant risk factor for all-cause death (Hazard ratio (HR), 7.09; 95% confidence interval (CI), 2.01-15.69, p&amp;lt;0.05) and for infectious disease death (HR, 16.9; 95% CI, 2.56-121.5, p&amp;lt;0.05). On the other hands, the preventive administration of Trimethoprim-Sulfamethoxazole (TS) decreased the risk of infectious disease death (figure 2). Conclusion The MPO-ANCA-related RPGN clinical grading system created by JSN was a useful tool for prediction of prognosis. Furthermore, TS should be administrated for all immune-suppressive patients to prevent variable infections not only Pneumocystis.

Does Trimethoprim-Sulfamethoxazole prophylaxis induce myelosuppression in primary immune deficiency disease patients; A retrospective, 3 groups comparative study.

The possible myelosuppression side effect of Trimethoprim-Sulfamethoxazole (TMP-SMX) on primary immune deficiency (PID) patients has not been established yet. Identify if the PID patients are at higher risk of developing myelosuppression secondary to the use of TMPSMX. Retrospective, three groups study, of PID patients (on and off TMP-SMX prophylaxis) and urinary tract infection (UTI) patients received prophylaxis TMP-SMX. Data about CBC results (WBC, ANC, Lymphocytes, RBC, Hemoglobin, and Platelet counts) at baseline, first, and maximum myelosuppression observed during the period of TMP-SMX administration were collected. A total of 122 patients were included in this study (41 PID patients on TMP-SMX prophylaxis, 45 PID patients not on TMP-SMX prophylaxis, and 36 UTI patients on prophylaxis TMP-SMX). There are significant differences noticed in the percentage of patients who developed clinical myelosuppression (i.e. less than normal value for age) in ANC (39.0% vs. 8.9% vs. 16.7%, p = 0.002), RBC (36.6% vs. 13.3% vs. 13.9%, p = 0.014), WBC (41.5% vs. 13.3% vs. 13.9%, p = 0.003), and platelet (24.4% vs. 15.6% vs. 2.8%, p = 0.028) in group 1, 2, and 3, respectively. Significant difference in myelosuppression between the groups was most likely due to the combination of TMP-SMX effect on PID patients rather than the disease or the drug itself. Primary immune deficiency (PID) patients are at higher risk of developing myelosuppression secondary to TMP-SMX prophylaxis (especially ANC) comparing to immune-competent patients or other PID patients who did not receive prophylactic TMP-SMX. Future larger prospective study is required to confirm this association.

Prevention of Opportunistic Infections in Women With HIV Infection

Opportunistic infections are those that are either more frequent or more severe as a result of the patient's immunosuppressed condition. Opportunistic infections are, of course, the distinguishing feature of HIV infection, and they can be the cause of serious morbidity and even mortality. Some opportunistic infections can be prevented by vaccination, for example, pneumococcal infection, meningococcal infection, influenza, hepatitis A and B, and varicella. Other major opportunistic infections require prophylactic antibiotics or antiviral medications. In obstetric patients, pneumocystis infections and toxoplasmosis are most effectively prevented by the administration of trimethoprim-sulfamethoxazole. The most effective agents for prevention of reactivation of tuberculosis are isoniazid, rifampin, and rifapentine. Fluconazole is of value in preventing cryptococcal infection and candidiasis. Acyclovir, valacyclovir, and famiclovir are effective in preventing recurrent outbreaks of herpes simplex virus. Ultimately; however, the best way to prevent opportunistic infections is to treat the patient with highly active antiretroviral agents and restore her immune competence.

The Authors' Reply.

Our recent study showed that the contagious nature of Pneumocystis jirovecii allows development of outbreaks of Pneumocystis pneumonia (PCP) in immunosuppressed kidney transplant recipients without prophylaxis. Although short-term prophylaxis at developing of PCP is effective in controlling transient outbreak, recurrence of PCP outbreak may arise under free anti-Pneumocystis regimens. We asserted that implementation of lifelong prophylaxis is required for prevention of repeated PCP outbreak in kidney transplant recipients.1 A recent Letter to the Editor by Momoko Kono, MD, et al: “A case of a Pneumocystis pneumonia twenty-four years after living kidney transplantation due to withdrawal of Sulfamethoxazole/Trimethoprim prophylaxis” supports our study.2 Guidelines for kidney transplant recipients recommend anti-Pneumocystis prophylaxis for all recipients for at least 6 to 12 months posttransplant. However, this is only directed to protect individuals against PCP infection soon after transplantation, but not for long-term prevention of PCP outbreak. Because kidney transplant recipients account for the largest proportion of organ transplant recipients, they are at high risk of exposing each other through their contact in the outpatient clinic. Once a patient developed PCP in these populations, who are taking standard immunosuppression, an outbreak of PCP may easily occur. Although a 3-month prophylaxis provided to all recipients (universal short-term prophylaxis) is sufficient to control the outbreak, intermittent new PCP outbreaks caused by different genotypes are not prevented in our experience.1 There are 3 ways of acquiring PCP: (1) via direct transmission from patients with active PCP, (2) from asymptomatic carriers, or from (3) environmental exposure. P. jirovecii is currently classified as a fungus, not a protozoan. Because a culture system for P. jirovecii in vitro has not yet been established, the life cycle of P. jirovecii remains poorly defined. Pneumocystis organisms differ depending on mammalian species, so that strains from one host mammal do not transmit to a different one. Reports of evidence for the cysts as the agent of transmission of P. jirovecii have also been shown by aerial route from host to host in mice.3,4 Accordingly, the reasons for emergence of PCP among immunocompromised host can be explained by the reactivation developing from de novo infection or reinfection with different genotypes. In PCP lungs, trophic forms are the most abundant, whereas cysts which are detected in the bronchial lumen may be the major form through colonization. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the first drug of choice for PCP prophylaxis, as well as for treatment. The TMP-SMX is an antiprotozoal agent, not meant to target fungus, but is highly effective for PCP (trophic forms) treatment. Unlike trophic forms, as cysts are not sensitive to TMP-SMX, colonies of P. jirovecii in the bronchial lumen cannot be eliminated. Macrophages which are phagocytic immune cells have a function for clearance of activated P. jirovecii, but those in kidney transplant recipients are basically suppressed. Thus, susceptible kidney transplant patients are ready to import any genotypes of P. jirovecii that they are exposed to in the outpatient clinic. Although short-term administration of TMP-SMX effectively blocks the onset of PCP which changes from cysts to trophic forms, it is impossible to eradicate the nest of P. jirovecii. Therefore, lifelong administration could be approved to protect recipients from PCP outbreaks by different genotypes in a transplant facility where many immunosuppressed patients visit. Previously, we experienced repeated outbreaks of PCP in the past decade, but no PCP outbreaks have been observed over a 40-month period after a lifelong prophylaxis strategy was adopted in our kidney transplant center.

Syndrome of Inappropriate Antidiuretic Hormone Secretion Complicating Systemic Nocardiosis in a Renal Transplant Recipient: A Case Report

BackgroundInfection by Nocardia species is an uncommon cause of severe clinical syndromes, particularly in immunocompromised patients, and solid-organ transplantation is the most common underlying condition. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been described thus far in lung and stem cell transplants with systemic nocardiosis. Case ReportWe report the first case of SIADH in a female elderly renal transplant recipient diagnosed with systemic nocardiosis 2 years after transplantation. The SIADH was managed appropriately, and her immunosuppressive regimen remained unchanged but was adjusted at a lower level. The systemic Nocardia infection was successfully treated with intravenous administration of trimethoprim-sulfamethoxazole and imipenem for 2 weeks followed by oral trimethoprim-sulfamethoxazole for a total of 12 months. ConclusionsThe SIADH syndrome is a recognizable complication of Nocardia infection in renal transplant recipients. Prompt identification along with proper management and prolonged antimicrobial treatment are essential to improve patients' outcome.

Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge.

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8+ T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis.

1455P - The primary prophylaxis of pneumocystis pneumonia by low-dose trimethoprim-sulfamethoxazole during R-CHOP therapy

Pneumocystis pneumonia (PCP) is frequently observed in immunocompromised patients. Currently, oral administration of trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 1 tablet daily (7 tablets/week) or 2 tablets twice a day, twice a week (8 tablets/week) is considered as standard for prophylaxis. However, they sometimes induce unpleasant toxicities such as rash, leukopenia and renal dysfunction. To avoid them, dose reduction of TMP-SMX could be considerable. Rituximab plus CHOP therapy (R-CHOP) is a standard treatment for B-cell lymphoma. Since rituximab is immunosuppressive, prophylaxis of PCP is widely introduced. In our institute, low-dose TMP-SMX has been employed in such situations. To assess the efficacy and tolerability of the regimen, retrospective analysis was performed. We reviewed patients with newly diagnosed B-cell lymphoma who completed 6 to 8 cycles of R-CHOP in our institute. In all patients, low-dose TMP-SMX consisting of 1 tablet twice a day, twice a week (4 tablets/week) was started simultaneously with R-CHOP. To improve medication adherence, administration day was fixed on Tuesday and Friday. From January 2009 to September 2014, 292 patients with a median age of 67 (21-89) were treated. They included diffuse large B-cell lymphoma (n = 213), follicular lymphoma (n = 65), mantle cell lymphoma (n = 6) and others (n = 8). The median length of prophylaxis from the last day of R-CHOP was 5.7 (0.6-16.6) months. The median lymphocyte count decreased from 1.1 (0.07-19.2) to 0.4 (0.03-1.4) x 109/L during treatment. Of 292 patients, 291 showed no evidence of PCP. Although 1 patient developed PCP, the diagnosis was given on day 12 of the first cycle indicating that the patient already had PCP before the initiation of prophylaxis. In the other 291 patients, TMP-SMX was well tolerated and no related adverse event was observed. Four tablets of TMP-SMX a week may be sufficient to prevent PCP during R-CHOP. In addition, minimum toxicities are expected by this method. As demonstrated in our study, the elderly patients who need R-CHOP are increasing. In this context, our data provide a valuable insight into the total strategy of lymphoma treatment.