Treating AIDS-associated cerebral toxoplasmosis - pyrimethamine plus sulfadiazine compared with cotrimoxazole, and outcome with adjunctive glucocorticoids.

We conducted a retrospective study of AIDS-associated cerebral toxoplasmosis. Eighteen patients received pyrimethamine plus sulfadiazine and 25 co-trimoxazole, with comparable baseline characteristics. There were no differences in clinical outcomes, but co-trimoxazole was better tolerated (p = 0.066). There was also a trend towards more deaths among patients who received glucocorticoids.     

Intracerebral toxoplasmosis in patients with acquired immune deficiency syndrome

The acquired immune deficiency syndrome (AIDS) is a recently described T-cell deficiency predisposing patients to a spectrum of opportunistic infections. Kaposi's sarcoma, and other neoplasms. It appears primarily among homosexual males and intravenous drug abusers, but is now being observed in other groups as well. The authors describe six adult patients with AIDS who developed intracranial toxoplasmosis. In four patients, diagnosis was made by brain biopsy, and in one by serology. These patients received a 90-day course of therapy with sulfadiazine, pyrimethamine, or both when tolerated, and improved neurologically. In one patient, the brain biopsy was nondiagnostic and the organism was identified at autopsy. On computerized tomographic and pathological follow-up studies the organism appeared to be eradicated by therapy. Early aggressive diagnostic study and prompt institution of therapy are imperative for reversal of neurological deficits. Despite cure of toxoplasmosis, the prognosis in patients with AIDS is poor; the mortality in this series was 67%. Isolation precautions should be taken by those caring for such patients.     

Cerebral toxoplasmosis

Opinion statement The choice of drugs for treating cerebral toxoplasmosis is limited. There are only three drugs available, and, of these, pyrimethamine and sulfonamide are invariably used in combination. Clindamycin is an alternative choice. Another drug, spiramycin, has poor central nervous system penetration, but achieves high concentrations in the placenta, and it is useful for treatment of toxoplasmosis during pregnancy. Because long-term maintenance therapy is often necessary, particularly in patients with AIDS, a wider choice of antibiotics is urgently necessary, because of potential problems with drug resistance and side effects. Treatment may be started empirically in any patient with HIV infection and multiple brain lesions. The drugs of choice are a combination of sulfadiazine and pyrimethamine. Folinic acid should be added to prevent pyrimethamine-induced bone marrow suppression. Repeated neuroimaging, 2 weeks after initiating therapy, is needed to assess efficacy of treatment. If CD4 cell counts remain below 100 cells per mm3, lifelong therapy is needed. Tissue diagnosis should be established in patients who do not respond to treatment, who have solitary lesions, or in patients without AIDS. Recent breakthroughs in the understanding of the biology of Toxoplasma will result in the development of a range of new therapies in the near future.     

Early experience and difficulties with bronchoalveolar lavage and transbronchial biopsy in the diagnosis of AIDS associated pneumonia in Britain.

Bronchoalveolar lavage and transbronchial biopsy have been used as adjuncts to the management of patients with pneumonia associated with the acquired immunodeficiency syndrome (AIDS) at the Middlesex Hospital and the experience gained and difficulties encountered in the first five cases are reported. Widely varying organisms were isolated from lavage aspirates, some of which may have been nasopharyngeal contaminants, and organisms cultured from the transbronchial biopsy specimens may offer a better guide to antimicrobial treatment. Pneumocystis carinii was found in two of the patients. In view of the potentially serious toxicity of high dose co-trimoxazole, continuation of this treatment may be inadvisable if Pneumocystis carinii is not identified by all available methods unless there are strong clinical grounds to suspect its presence.     

Co-trimoxazole and trimethoprim in complicated urinary tract infection

Previous work has suggested that co-trimoxazole may be superior to trimethoprim in the treatment of complicated urinary tract infection. A prospective study has been done to assess the relative value of the drugs in this situation using trimethoprim at higher than normal dosage. Fifty three patients (33 women and 20 men) were randomly allocated to either a fourteen-day course of co-trimoxazole tabs, 2 twice a day (27 patients) or trimethoprim 250 mg twice a day (26 patients). After patient withdrawals from the study, 17 (77%) of the co-trimoxazole group achieved a sterile urine three weeks after starting treatment compared with 15 (65%) in the trimethoprim group (X2 = 0.80). When those patients with sterile urine at three weeks who could be reassessed four weeks later were analyzed, 8 (89%) of the co-trimoxazole patients maintained a sterile urine against 7 (58%) in the trimethoprim group (X2 = 1.09). Although statistical significance was not attained, the results suggest that even at increased dosage, trimethoprim would not appear to be as efficient as co-trimoxazole in complicated urinary tract infection.     

Comparison of cefixime and co-trimoxazole in acute uncomplicated urinary tract infection. A double-blind general practice study

Five hundred and twenty-eight patients with presumptive acute uncomplicated urinary tract infection (UTI) were randomly assigned to receive cefixime 400 mg once daily, cefixime 200 mg twice daily or co-trimoxazole 2 tablets twice a day for 10 days; 477 completed at least 5 days of therapy. Of the patients 342 (65%) had positive baseline urine cultures, yielding 353 pathogens. A microbiological response was determined for 280 pathogens (79%), eradication being observed in over 94% of isolates; 153 pathogens (43%) were sensitive to both cefixime and co-trimoxazole and eradication was observed in over 96% of cases. Clinical response correlated well with microbiological response. The incidence of diarrhoea and stool changes was higher (P less than 0.005) in the patients who received cefixime once daily than in the other groups. There was a significantly higher incidence of stool changes with cefixime twice daily than with co-trimoxazole (P less than 0.05), but these did not necessitate discontinuation of therapy. Nausea was commoner with co-trimoxazole (P less than 0.05). The majority of pathogens isolated were Escherichia coli, Proteus mirabilis and staphylococci. Approximately 24% of E. coli were resistant in vitro to co-trimoxazole (P less than 0.005). Cefixime 200 mg twice daily is an effective and safe alternative to co-trimoxazole in the management of acute uncomplicated UTI.     

Treatment of peritonitis in continuous ambulatory peritoneal dialysis patients with co-trimoxazole

Peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) represents the most frequent and difficult problem related to this new form of treatment of ESRD patients. Various treatments have been reported previously. The aim of this study was to investigate the efficiency of a standardized initial treatment in 45 episodes of peritonitis. This was designed to be rapidly efficient, devoided of side-effects and easy enough to be performed by the patients themselves. When peritonitis was clinically suspected, patients received intraperitoneal co-trimoxazole (80 mg trimethoprim, 400 mg sulfamethoxazole), in each of the four daily bags concomitantly with 1,000 U heparin during 2 weeks and half of this dose during 2 other weeks. Our results demonstrate that 88% of the isolates were sensitive to co-trimoxazole and 85% of the patients completed this treatment. All were cured and no relapses were observed. Only 18 days of hospitalisation were required in the 45 episodes of peritonitis. Another anti-infective agent was used in 3 cases of gram-negative peritonitis and 4 other initially resistant to co-trimoxazole. It is concluded that initial treatment of CAPD peritonitis with co-trimoxazole is justified by the high proportion of sensitive germs and that it represents a safe, efficient and inexpensive treatment.     

Selective intestinal decontamination for prevention of wound colonization in severely burned patients: a retrospective analysis.

In this study the effect of selective intestinal decontamination of the digestive tract (SDD) on wound colonization was investigated. Ninety-one patients with at least 25 per cent total burned surface area (TBSA) were included in this study. All patients received oral polymyxin. In 63 patients oral co-trimoxazole and amphotericin B were added to the regimen. The addition of co-trimoxazole decreased the incidence of Enterobacteriaceae wound colonization from 71 per cent to 11 per cent (P less than 0.005). Colonization with Proteus was eliminated in patients treated with co-trimoxazole, compared with an incidence of 36 per cent in the group treated with polymyxin alone (P less than 0.001). The addition of amphotericin B decreased yeast colonization of the burn wound from 39 per cent to 10 per cent (P less than 0.005). A close relation was observed between burn wound colonization and colonization of the gastrointestinal tract. No resistant bacterial strains emerged during the period of study. These results suggest that SDD is an effective method for prevention of wound colonization. Further controlled studies are needed to establish the role of SDD in preventing burn wound colonization and wound sepsis.     

Efficacy of pyrimethamine for the prevention of donor-acquired Toxoplasma gondii infection in heart and heart-lung transplant patients

Seven (11%) of the first 65 patients who received heart transplants at Papworth Hospital were mismatched for Toxoplasma gondii. Of these, four (57%) experienced T. gondii infection and two died. The remaining two had severe symptoms and received anti-T-gondii chemotherapy for a year after transplantation. In an attempt to reduce the impact of donor-acquired T. gondii in our heart transplant recipients, we decided in April 1984 to give prophylactic pyrimethamine to all T. gondii-mismatched patients. In this study, 7 years later, we review the efficacy of this policy. Five of 37 (14%) patients given prophylactic pyrimethamine acquired T. gondii infection; only one was symptomatic, and none died. This compares with 100% symptomatic infection in the pre-1984 patients, who did not receive prophylactic pyrimethamine. We believe that our experience has shown that pyrimethamine is effective in reducing the incidence and severity of primary donor-acquired T. gondii infection in mismatched heart and heart-lung transplant recipients.     

Empirical treatment without bronchoscopy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

An empirical approach to treating Pneumocystis carinii pneumonia was adopted in a prospective study of 73 men with antibodies to human immunodeficiency virus 1 (HIV-1) presenting with respiratory problems. At presentation 49 patients (group 1) were thought to have a history, findings at clinical examination, chest radiograph, and arterial blood gas tensions typical of pneumocystis pneumonia, and empirical treatment was begun immediately. Twenty four patients (group 2) were thought to have features not typical of pneumocystis pneumonia. All patients were subsequently referred for bronchoscopy to determine the diagnosis. In group 1 four patients were excluded from the analysis because bronchoscopy was not possible. Of the remaining 45, 42 had pneumocystis pneumonia, which was diagnosed at bronchoscopy in 40, and on the basis of the clinical response to co-trimoxazole in two who had negative results from investigations. Of the three patients without pneumocystis pneumonia, one patient with lymphoid interstitial pneumonitis and Branhamella catarrhalis infection would have failed to respond to empirical treatment. The other two had multiple bacterial pathogens at bronchoscopy; one already had Kaposi's sarcoma and the other would have been misdiagnosed as having AIDS. In group 2 a specific diagnosis was made at bronchoscopy in 21 cases, including pneumocystis pneumonia in seven (all had atypical chest radiographs). In three cases no diagnosis was made and spontaneous recovery occurred. Adopting an empirical approach to treatment for typical pneumocystis pneumonia (group 1) led to the correct treatment in 43 of 45 cases (95%) and would have saved 44 of the 45 of bronchoscopies in this group. Adopting an empirical approach would have caused one patient to be misdiagnosed as having AIDS. Overall, 44 out of 69 bronchoscopies (64%) would have been saved; the specificity for the diagnosis of pneumocystis pneumonia was 85% and the sensitivity was 85%. Adopting an "empirical" treatment policy for typical pneumocystis pneumonia will cause a large reduction in the number of "high risk" bronchoscopies performed.     

Co-administration of Co-trimoxazole Does Not Augment Tacrolimus-Induced Impairment in Kidney Function in Rats

Co-trimoxazole is an antibiotic that is frequently used in organ transplant patients. Our objective was to determine the effect of co-trimoxazole on tacrolimus-mediated functional impairment of the kidney in rats. Sprague Dawley rats were divided into three groups. Group 1 (dextrose) received 5% dextrose and Group 2 (tacrolimus) received tacrolimus (1 mg/kg/day) as a continuous intravenous infusion for seven days. Group 3 (combination) received tacrolimus as above and co-trimoxazole (30 mg/kg/day trimethoprim and 150 mg/kg/day sulfamethoxazole) intraperitoneally for six or seven days. Biochemical and functional parameters were measured pre- and post-drug infusion. On day 7, glomerular filtration rate (GFR) was evaluated using ³H-inulin. while the effective renal plasma flow (ERPF)/cationic tubular secretion was assessed using ¹⁴C-tetraethylammoniumbromide (TEA).

GFR (mL/min/kg) as measured by inulin clearance was higher (p ≤ 0.05) in the dextrose (12.0 ± 1.4) group as compared to tacrolimus group (6.0 ± 1.3) and combination group (6.4 ± 1.6), but there was no difference between the tacrolimus and combination group. ERPF/cationic tubular secretion (mL/min/kg) was also significantly higher in the dextrose group (62.6 ± 10.3) as compared to the other two groups. ERPF/cationic tubular secretion was not different between the combination (33.3 ± 5.9) and the tacrolimus (35.1 ± 6.7) groups when there was no co-trimoxazole in the body. However, in the presence of co-trimoxazole ERPF/cationic tubular secretion was significantly reduced in the combination (23.1 ± 3.5) group as compared to the tacrolimus group (35.1 ± 6.7).

These results indicate that co-trimoxazole does not further potentiate tacrolimus induced impairment in kidney Junction but is likely to further inhibit cationic tubular secretion in patients on tacrolimus therapy.     

Kelfiprim versus co-trimoxazole in recurrent and persistent urinary tract infections: multicenter double-blind trial

Kelfiprim (KP) is a new bactericidal agent containing trimethoprim (T) and sulfametopyrazine (S), a long-acting sulfonamide (ratio 5:4). The posology is one capsule (T 250 mg + S 200 mg) daily, after a loading dose of two capsules on the first day. To evaluate the clinical value of Kelfiprim (KP) vs co-trimoxazole (CO) in urinary tract infection (UTI) a controlled multicenter double-blind trial (MDBT) was carried out in 76 patients suffering from persistent and recurrent UTIs. About 90 per cent response rate (sterile urine at the end of treatment) was obtained for KP and about 85 per cent for CO in recurrent UTI. In persistent UTI the rate of recovery was 66.8 per cent and 53 per cent for KP and CO, respectively. Safety of treatments was excellent in 97 per cent of patients treated with Kelfiprim and 87 per cent treated with co-trimoxazole. Two patients, one in each group, were dropped from the study because of adverse reactions.     

A comparison of cephazolin sodium and co-trimoxazole as prophylactic antibiotics in out-patient urinary tract endoscopy

Five-hundred patients were entered into a study to compare intramuscular cephazolin sodium with intramuscular co-trimoxazole in reducing the incidence of post-endoscopy rigor in out-patients. Urine cultures were carried out immediately before, immediately after, and 24 h after endoscopy and the incidence of post-procedure symptoms was elicited by pre-paid reply post cards. Similar rigor rates (9%) were obtained in the 2 groups. The incidence of sensitivity of the significant cultured organisms to the 2 antibiotics was high, but no correlation was found between the presence of infected urine and rigor, and possible reasons for this are discussed. Patients found intramuscular administration of co-trimoxazole to be painful and the 10% incidence of rigor is no improvement on the 8% rigor rate obtained in those who received cephazolin.     

Co-administration of co-trimoxazole does not augment tacrolimus-induced impairment in kidney function in rats

Co-trimoxazole is an antibiotic that is frequently used in organ transplant patients. Our objective was to determine the effect of co-trimoxazole on tacrolimus-mediated functional impairment of the kidney in rats. Sprague Dawley rats were divided into three groups. Group 1 (dextrose) received 5% dextrose and Group 2 (tacrolimus) received tacrolimus (1 mg/kg/day) as a continuous intravenous infusion for seven days. Group 3 (combination) received tacrolimus as above and co-trimoxazole (30 mg/kg/day trimethoprim and 150 mg/kg/day sulfamethoxazole) intraperitoneally for six or seven days. Biochemical and functional parameters were measured pre- and post-drug infusion. On day 7, glomerular filtration rate (GFR) was evaluated using 3H-inulin while the effective renal plasma flow (ERPF)/cationic tubular secretion was assessed using 14C-tetraethylammoniumbromide(TEA). GFR (mL/min/kg) as measured by inulin clearance was higher (p < or = 0.05) in the dextrose (12.0 +/- 1.4) group as compared to tacrolimus group (6.0 +/- 1.3) and combination group (6.4 +/- 1.6), but there was no difference between the tacrolimus and combination group. ERPF/cationic tubular secretion (mL/min/kg) was also significantly higher in the dextrose group (62.6 +/- 10.3) as compared to the other two groups. ERPF/cationic tubular secretion was not different between the combination (33.3 +/- 5.9) and the tacrolimus (35.1 +/- 6.7) groups when there was no co-trimoxazole in the body. However, in the presence of co-trimoxazole ERPF/cationic tubular secretion was significantly reduced in the combination (23.1 +/- 3.5) group as compared to the tacrolimus group (35.1 +/- 6.7). These results indicate that co-trimoxazole does not further potentiate tacrolimus induced impairment in kidney function but is likely to further inhibit cationic tubular secretion in patients on tacrolimus therapy.     

Short-term treatment of patients with chronic and recurrent urinary tract infections with co-trimoxazole

Summary A study is presented in which patients with recurrent urinary tract infections with and without anatomical defects or obstructive diseases are treated with a short-term, high-dosage followed by a short-term, low-dosage regimen of co-trimoxazole.     

Co-trimoxazole prophylaxis for children who are HIV-exposed and uninfected: a systematic review

Introduction

Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.

Methods

We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.

Results

We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2–6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.

Discussion

Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.

Conclusions

In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.     

A study of concentrations of trimethoprim-sulphamethoxazole in the human prostate gland.

The ability of trimethoprim (TMP) and sulphamethoxazole (SMX) components of co-trimoxazole to penetrate the human prostate gland was investigated. After a single 4-tablet dose TMP was evenly distributed between prostate and plasma, whereas SMX was mainly associated with plasma. Following a week's therapy significant accumulation of TMP was seen in the prostate relative to plasma whereas SMX although still associated with plasma had increased drug levels in prostate compared with the single dose study. It is concluded that co-trimoxazole produces effective antibacterial levels in the human prostate and has indications in the treatment of prostatitis.     

Chloroquine resistance in Plasmodium falciparum in Natal

Out of 110 cultures of Plasmodium falciparum obtained from infected patients in Natal 18 were found to be resistant to chloroquine by in vitro tests: 2 cultures showed schizont development in wells containing 24 pmol chloroquine; in 16 schizont development was present in culture wells containing 48 pmol chloroquine. Seventy-two patients with P. falciparum malaria who apparently did not respond to adequate oral chloroquine therapy were investigated. All responded to one or more treatments with pyrimethamine/sulphadoxine (Fansidar; Roche). It would seem that all the patients were infected in areas not controlled by the South African health authorities.     

Outcomes of laparoscopic and open appendectomy for acute appendicitis in patients with acquired immunodeficiency syndrome

The aims of this study were to compare outcomes of appendectomy between acquired immunodeficiency syndrome (AIDS) and nonAIDS patients and laparoscopic appendectomy (LA) versus open appendectomy (OA) in AIDS patients. Using the Nationwide Inpatient Sample database, from 2006 to 2008, clinical data of patients with AIDS who underwent LA and OA were evaluated. A total of 800 patients with AIDS underwent appendectomy during these years. Patients with AIDS had a significantly higher postoperative complication rate (22.56% vs 10.36%), longer length of stay [(LOS) 4.9 vs 2.9 days], and higher mortality (0.61% vs 0.16%) compared with non-AIDS patients. In nonperforated cases in patients with AIDS, LA was associated with a significantly lower complication rate (11.25% vs 21.61%), lower mortality (0.0% vs 2.78%), and shorter mean LOS (3.22 days vs 4.82 days) compared with OA. In perforated cases in patients with AIDS, LA had a significantly lower complication rate (27.52% vs 57.50%), and shorter mean LOS (5.92 days vs 9.67 days) compared with OA. No mortality was reported in either group. In patients with AIDS, LA has a lower morbidity, lower mortality, and shorter LOS compared with OA. Laparoscopic appendectomy should be considered as a preferred operative option for acute appendicitis in patients with AIDS.     

The role of a palliative care inpatient unit in disease management of cancer and HIV patients.

OBJECTIVES: To monitor the success of an inpatient palliative care unit combining private and state patients, and accessible to patients with cancer and AIDS. DESIGN: An observational study was conducted of patients admitted to the unit in the first 3 months following opening of the ward (1 March - 31 May 2006). METHODS: Data were collected on all patients admitted to the ward to establish patient profiles, duration of stay and outcome of palliative care. RESULTS: In the first 3 months 51 patients were admitted. Of these patients, 36 (70%) (1 readmission) had AIDS. All the AIDS patients had stage 4 disease and all but 3 were on antiretroviral (ARV) treatment. The death rate in the initial 3 months was 38% in the cancer group and 33% in the AIDS group. By the end of the 5th month the death rate was 37.5% in the cancer group, and 27% in the AIDS group. The remainder of the patients were discharged. The average duration of stay in the ward was 8.3 days. Among those who died, the average stay was 3.8 days for cancer patients and 8.3 days for AIDS patients. Among the patients who were discharged, the average duration of stay was 7 days for cancer patients and 8.5 days for AIDS patients. CONCLUSIONS: The profile of terminally ill patients with cancer and AIDS was initially similar in terms of death rate. In the first 3 months 38% of cancer patients and 33% of AIDS patients died. In the following 2 months the death rate was 33% for cancer patients and 19% for AIDS patients. While the numbers of patients are small and only an indication of trend, the AIDS death rate seems to be dropping. This may be because ARV treatment is being introduced earlier, or because the role of palliative care in the treatment of AIDS patients is gaining recognition and introduction of this form of treatment is having a beneficial effect on outcome. In this hospital it is now accepted that AIDS patients developing symptoms on treatment will benefit from admission to a palliative care ward. This intervention may well improve the outcome in stage 4 AIDS. The duration of stay in the ward is longer for AIDS patients, and it appears that AIDS patients who survive will need a longer stay in the palliative care unit than cancer patients if outcome is to improve.