Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug

ABSTRACT Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Bullous cellulitis as an extraordinary manifestation of a Vibrio cholerae O1 Ogawa infection

@#Vibrio cholerae is a gram-negative bacterium synonymous with its namesake disease, cholera. Thus, gastrointestinal symptoms are the norm and V. cholerae is very rarely associated with skin and soft tissue infections. We describe a case of a 63-year-old Chinese woman with multiple medical comorbidities on corticosteroid therapy who developed fever and a painful swelling on her left leg after being pricked by a branch while gardening. There was no abdominal pain, vomiting or diarrhea. A diagnosis of bullous cellulitis was made clinically, and blood was sent for bacteriological culture. A beta-hemolytic commashaped gram-negative bacillus was isolated from the blood. It was also oxidase-positive and produced an acid/alkaline (A/K) reaction on triple sugar iron agar. It was identified biochemically as Vibrio cholerae. After additional testing, it was found to be of the O1 serogroup and Ogawa serotype. The infection resolved following a 10-day course of high-dose co-trimoxazole therapy.

Monday Blues - Rare Cause of Hypoglycemia in a Child with Leukemia

Hypoglycemia in a child with acute lymphoblastic leukemia (ALL) often makes the clinician think of sepsis or metabolic disturbances due to relative adrenal insufficiency with steroid withdrawal. We report a rare scenario of drug-induced hypoglycemia in a child on treatment for ALL. Recurrent symptomatic episodes of hypoglycemia in a 4-year-girl on treatment for high-risk ALL were analyzed and it was surprising to note that the episodes were noted on early hours on Monday and Sunday nights. Detailed evaluation for the etiology and the workup was not contributory. With the background of drug history for ALL maintenance and occurrence of episodes on Mondays, possibility of drug-induced hypoglycemia secondary to cotrimoxazole was considered. Dose alteration for trimethoprim-sulfamethoxazole was considered stopping the drug is not feasible. Malnutrition was attributed as the coexisting risk factor in our child

Benefits and risks of prolonged cotrimoxazole prophylaxis among people living with HIV in immune reconstitution phase: A retrospective cohort study

@#<p style="text-align: justify;"><strong>OBJECTIVES:</strong> To determine the effect of prolonged cotrimoxazole prophylaxis (CP) in reducing hospitalization and opportunistic infection rates among people living with HIV (PLHIV) with CD4 count >200 cells/mm3.<br /> <strong>METHODS:</strong>  We retrospectively reviewed 349 medical charts of PLHIV with CD4 count (or T-cell count) of >200 cells/mm3 enrolled in an HIV treatment hub in Manila, Philippines, from January 2004 to July 2016. Demographic, clinical characteristics and outcomes were extracted. Descriptive statistics were generated. Chi-square test for two proportions was done to compare the difference in outcomes between the CP and non-CP groups.<br /> <strong>RESULTS:</strong>  Of the 349 patients, majority (96.6%) were male with a mean age of 28 years (SD 6.4) and mean CD4 count of 373 cells/mm3 (SD 148). CP was continued in 103 patients (29.5%) with mean duration of 1.7 (SD 1.9) years. The prolonged CP group had more events of adverse drug reactions (p<0.001), specifically minor cutaneous reactions (p<0.001) and immunologic failures (p<0.001), compared to the non-CP group. There were no statistically significant differences in the frequency of hospitalization, PJP (Pneumocystis jirovecii pneumonia), non-PJP, other respiratory illnesses, diarrhea, toxoplasmosis, tuberculosis, stage 3/4 events and mortality, between the prolonged CP and non-CP groups.<br /> <strong>CONCLUSION:</strong> We did not observe any additional benefit in giving prolonged CP among PLHIV with CD4 count >200 cells/mm3. More adverse effects were also seen in the CP group.</p>

The crucial role of molecular testing to facilitate the diagnosis of pneumocystis pneumonia during pregnancy

Pneumocystis pneumonia is an important human immunodeficiency virus (HIV)-associated opportunistic infection, and especially so in pregnant HIV-positive patients. We report a case of a 40-year-old woman in her first trimester of pregnancy who initially presented with acute gastroenteritis symptoms but due to a history of high-risk behaviour and the observation of oral thrush, she was worked up for HIV infection. Her retroviral status was positive and her CD4+ T cell count was only 8 cells/mL. She was also worked up for pneumocystis pneumonia due to the presence of mild resting tachypnoea and a notable drop in oxygen saturation (from 100% to 88%) following brief ambulation. Her chest radiograph revealed bilaterally symmetrical lower zone reticular opacities and Giemsa staining of her bronchoalveolar lavage (BAL) was negative for Pneumocystis jirovecii cysts. However, real-time P. jirovecii polymerase chain reaction (PCR) testing on the same BAL specimen revealed the presence of the organism. A course of oral co-trimoxazole plus prednisolone was commenced and her clinical condition improved.

Características clínicas y microbiológicas de las infecciones de piel y tejidos blandos por Staphylococcus aureus en niños de un hospital en Medellín durante los años 2013 a 2015 / Clinical and microbiological characteristics of skin and soft tissue infections caused by Staphylococcus aureus in children in a hospital in Medellin from 2013 to 2015

Resumen Introducción: El principal microorganismo implicado en las infecciones de piel y tejidos blandos (IPTB) es Staphylococcus aureus, con incremento en las cepas resistentes a meticilina en los últimos años. Objetivo: Identificar la frecuencia de S. aureus resistente a meticilina (SARM) en IPTB en niños que consultaron a un hospital de cuarto nivel en la ciudad de Medellín. Métodos: Estudio descriptivo, retrospectivo, a partir de la revisión de historias clínicas. Se incluyeron pacientes menores de 18 años con IPTB causadas por S. aureus que no cumplieran con criterios de enfermedad invasora. Resultados: La prevalencia de SARM en esta población fue de 31%. El principal diagnóstico fue absceso cutáneo (68%), seguido por infección de sitio quirúrgico (15%) y celulitis no purulenta (6%). Tenían alguna co-morbilidad 85% de los pacientes. Todos los aislados fueron sensibles a rifampicina y cotrimoxazol. Ocho por ciento de los aislados fueron resistentes a clindamicina. Se encontró mayor prevalencia de SARM en lactantes comparado con los mayores de 2 años (60 vs 23%, p = 0,0109). Conclusión: Ante la alta prevalencia de SARM en IPTB se recomienda incluir en el tratamiento empírico antimicrobianos con cobertura para estas cepas, principalmente para lactantes.

Background: Skin and soft tissue infections (SSTI) are very common in children and Staphylococcus aureus is the main agent, with an increase of methicillin resistant strains (MRSA) in recent years. Aim: To identify the frequency of MRSA in skin and soft tissue infections (SSTI) in children from a high complex hospital in Medellin, Colombia. Methods: This is a descriptive, retrospective study, information was obtained from medical records. We included patients younger than 18 years with SSTI due to S. aureus who did not meet criteria for invasive disease. Results: The prevalence of MRSA in this population was 31%. The main diagnosis was cutaneous abscess (68%), followed by surgical site infection (15%) and non-purulent cellulitis (6%). Eighty five percent of the patients had at least 1 comorbidity. All isolates were sensitive to rifampicin and cotrimoxazole and 8% of the isolates were resistant to clindamycin. There was a higher prevalence of MRSA in patients under 2 years compared to older (60 vs 23%, p = 0,0109). Conclusion: In view of the high prevalence of MRSA in SSTI, empirical treatment with adequate coverage for MRSA is recommended, especially for patients under 2 years of age.

Necrólisis tóxica epidérmica inducida por cotrimoxazol / Epidermic toxic necrolysis induced by co-trimoxazole

Se describe el caso clínico de una paciente de 60 años de edad con antecedentes de hipertensión arterial, por lo cual llevaba tratamiento con nifedipino, quien asistió al Cuerpo de Guardia del Hospital General Docente "Orlando Pantoja Tamayo" en el municipio de Contramaestre, Santiago de Cuba, por presentar deposiciones diarreicas, vómitos, hipertermia (38 0C) y lesiones generalizadas en la piel en forma de pústulas eritemato-costrosas con flictenas y dolor. La paciente refirió que solía automedicarse con cotrimoxazol por la reiteración de infecciones urinarias y que desde hacía 3 días estaba consumiendo dicho medicamento. El estudio histopatológico mostró una necrólisis tóxica epidérmica (síndrome de Lyell). A pesar de los cuidados médicos, evolucionó desfavorablemente y se complicó con una insuficiencia renal aguda, lo que le condujo a la muerte

The case report of a 60 years patient with a history of hypertension, reason why she had treatment with nifedipine, who went to the Emergency Room of "Orlando Pantoja Tamayo" Teaching General Hospital in Contramaestre, Santiago de Cuba, due to diarrheical stools, vomits, hyperthermia (38 0C) and generalized skin injuries in the type of erythemato-scabby pustules with flictenas and pain is described. The patient referred that she was accustomed to self-medication with co-trimoxazole due to repeated urinary infections and that she was consuming this medication for 3 days. The pathological study showed an epidermic toxic necrolysis (Lyell syndrome). In spite of the medical cares, she had an unfavorable clinical course and she complicated with an acute renal failure, leading to death

Efflux Pump Inhibitor Carbonyl Cyanide-m-chlorophenylhydrazone (CCCP) Enhances Bacteriostatic Activity of Trimethoprim-sulfamethoxazole Against Clinical Stenotrophomonas maltophilia Isolates from Korea

Although trimethoprim-sulfamethoxazole (TMP-SXT) is considered the first-line therapy for Stenotrophomonas maltophilia infections, there is debate on the use of the bacteriostatic drug in serious infections, and recently, there has been an increasing occurrence of acquired resistance to TMP-SXT. In the present study, the effect of efflux pump inhibitors on the susceptibility of TMP-SXT and other antibiotics were investigated in S. maltophilia complex. The sul and/or dfrA genes were identified in only up to 27.8% of all 36 TMP-SXT-resistant S. maltophilia complex isolates. Thus, TMP-SXT resistance in S. maltophilia was not explained completely by the presence of sul and dfrA genes. Carbonyl cyanide-m-chlorophenylhydrazone (CCCP) decreased the minimum inhibitory concentration (MIC) of TMP-SXT by eight to 128 folds in all 14 isolates. In contrast, 2,4-dinitrophenol (DNP), phenyl-arginine-β-naphthylamide (PAβN), and reserpine did not reduce the MIC of TMP-SXT. In addition to TMP-SXT, slight decrease in MICs was observed for tigecycline and piperacillin/tazobactam by CCCP (by two folds) in one isolate. Although efflux pump may play a role in TMP-SXT resistance in S. maltophilia, inhibition of the efflux pump could be done by active proton pore.

Cotrimoxazol en infecciones óseas: toxicidad e impacto clínico y económico / Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact

Background: Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. Aims: To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. Methods: Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. Results: From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). Conclusions: Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Antecedentes: Cotrimoxazol es una alternativa en infecciones óseas pero se ha asociado al desarrollo de falla renal e hiperkalemia. Objetivo: Evaluar toxicidad renal, hiperkalemia, estadía y gastos hospitalarios y evolución clínica en un grupo de pacientes con infecciones óseas tratados con este compuesto. Pacientes y Métodos: Estudio retrospectivo-descriptivo de pacientes adultos con infecciones óseas confirmadas con cultivos y tratados con este compuesto. Seguimiento de creatinina y kalemia y búsqueda de factores de riesgo para hiperkalemia, comparación de gastos y estadía hospitalaria y análisis de eficacia clínica. Resultados: Desde el año 2011 al 2014 se identificaron 23 pacientes (promedio de edad 64,7 años). La prevalencia de diabetes mellitus tipo 2 (82,6%), enfermedad vascular periférica (47,8%) y amputaciones previas (43,5%) fue elevada. La mediana de la kalemia basal aumentó significativamente al primer control (4,35 a 4,9 mEq/L) al igual que la creatinina plasmática (0,9 a 1,1 mg/dL). Siete pacientes desarrollaron hiperkalemia (30,4%). Se suspendió cotrimoxazol en 10 casos (43,5%) y en 6 casos se postergó el alta. El uso de fármacos activos contra el sistema renina-angiotensina (FASRA) se asoció a hiperkalemia (OR 10,8 IC95 1,37-85; p < 0,05). La estadía hospitalaria fue mayor en el grupo con toxicidad a cotrimoxazol (mediana de 56 versus 30 días; p < 0,05) y los pacientes sin suspensión de terapia tuvieron menos gastos por fármacos (medianas de 563 vs 2.820 USD, p < 0,01). Conclusiones: El uso de cotrimoxazol debe ser monitorizado para detectar hiperkalemia o toxicidad renal y suspender su prescripción. Los pacientes que usan FASRA tienen mayor riesgo de hiperkalemia. La estadía y gastos hospitalarios por fármacos son menores en pacientes que toleran el cotrimoxazol.

Risk Factors for First-line Antiretroviral Treatment Failure in HIV-1 Infected Children Attending Jos University Teaching Hospital, Jos, North Central Nigeria.

Aim: To determine risk factors for first-line antiretroviral treatment failure in HIV-1 infected children attending Jos University Teaching Hospital, Jos. Study Design: Retrospective cohort study. Place and Duration of Study: Paediatric HIV clinic at the Jos University Teaching Hospital, Jos, between February 2006 and December 2010. Methodology: Data on demographic, clinical and laboratory variables for 580 HIV-1 infected children aged 2 months to 15 years on antiretroviral therapy (ART) were analysed. A comparison of the data on children with and without treatment failure was made. Variables associated with treatment failure in a univariate analysis were then fit in a multivariate logistic model to determine the factors that were associated with treatment failure. Results: The rate of treatment failure among the children was 18.8%. Previous antiretroviral drugs (ARV) exposure for treatment, not receiving cotrimoxazole prophylaxis before commencement of ART and having severe immune suppression at HIV diagnosis were the factors independently associated with treatment failure. Children with previous ARV exposure for treatment were 4 times more likely to fail treatment compared to those without previous exposure (AOR=4.20 (1.93-9.15); p <0.001). Children who did not receive cotrimoxazole prophylaxis were twice more likely to develop treatment failure compared to those who did (AOR=2.26 (1.06-4.79); p=0.03) and children with severe immune suppression at HIV diagnosis were twice more likely to develop treatment failure compared to those without severe immune suppression (AOR=2.34 (1.47-3.72); p<0.001). Conclusion: HIV-infected children with previous ARV exposure for treatment and severe immune suppression should be monitored closely and given frequent adherence counseling to minimize the risk of treatment failure. Cotrimoxazole prophylaxis should be encouraged in HIV-infected children while they await commencement of ART, which may improve ART adherence and thus reduce the risk of treatment failure.

Drug use evaluation of cotrimoxazole prophylaxis in people living with human immunodeficiency virus/acquired immune deficiency syndrome at Jimma University Specialized Hospital, Jimma, South West of Ethiopia, 2013.

Background: Drug use evaluation is a performance improvement method that focuses on evaluation and improvement of drug use processes to advice optimal patient outcomes. Pneumocystis carinii pneumonia (PCP) is the most common acquired immune defi ciency syndrome (AIDS) defi ning illness. Antibiotics being the most commonly prescribed group of drugs the problem of its overuse are a global phenomenon. Cotrimoxazole (CTX) preventive therapy (CPT) was shown effectively prevents PCP in patients with clinical evidence of immune suppression. CTX has been widely used as a treatment for common infections in many resource limited areas and as a result, CTX resistance among these pathogens has increased dramatically. In response to these problems, this study aims to evaluate the use CTX prophylaxis for opportunistic infections in human immunodefi ciency virus (HIV) patients at Jimma University Specialized Hospital (JUSH). Methods: The study was done with retrospective cross-sectional review of medical records of HIV patients who have been on CTX prophylaxis in the hospital during September 11, 2012-September 10, 2013. To maintain the validity of data, the whole 135 patient cards were included in the study within the specifi ed period. Data were collected from January 16, 2013 to February 15, 2013 using structured data collection format. Results: From the study subjects, 82 (60.74%) were females 85.93% of patients were used appropriate dose of CPT and 13.3% patients use CTX against contraindication. Regarding to adverse drug reactions (ADRs), 3.7% of patients were developed rash while 2.2% cases were developed nausea during the follow-up period of CPT. However, only 5.9% patients have documented information about ADR of CPT. On the top of this, CD4 count and hemoglobin test were done for 82.96%, 64.4% patients respectively during initiation of CPT. However, renal function tests were performed only for 2.96% of patients while initiating CPT. Conclusion: The use of CPT for people living with HIV/AIDS was found to be good in JUSH with regard to initiation and dosage. However, the practice of discontinuation of CTX, documentation of ADRs and follow-up for adverse effects of CTX should be improved by proper implementation and adhering to the national guideline of CPT.

Effect of co-trimoxazole prophylaxis used for AIDS patients under anti-retroviral therapy / 中华流行病学杂志

Objective To analyze the situation of survival among AIDS patients under co-trimoxazole prophylaxis as initial anti-retroviral therapy(ART),in Henan province during 2007-2011. Methods Information on AIDS patients receiving initial ART during 2007-2011 was collected from the Chinese HIV/AIDS Integrated Control System. Kaplan-Meier estimation was used to generate survival curves,and Cox proportional hazard regression model was used to determine associated factors of survival status. According to the previous CTX use before ART,the subjects were divided into 3 groups including who had never taken CTX,who had taken CTX and still taking now,who had taken CTX and not current taking. Results A total of 13 103 eligible AIDS patients were identified. 1 702 patients died within 6 years after the initiation of ART,with the mortality as 4.46/100 person year. Among the 455 patients who died within 3 months and 970 died within 12 months,the mortality rates were 14.15/100 person year and 7.78/100 person year,respectively. The Kaplan-Meier survival curves showed that the survival time and mortality of the patients who had taken CTX was longer AND lower than those patients who had never taken CTX when starting the ART program. Results from the log-rank test showed that the difference of two groups was statistically significant during 12 months after the ART(log-rank=5.15,P=0.02). After controlling for other variables,results from multivariable analysis of COX model showed that factors as age,gender,marital status,perion between confirmed diagnosis and receiving the ART,baseline CD4+T cells count,clinical stage,initial therapy schedule,date when starting the ART,number of symptoms at baseline,use of CTX before starting the ART and ART being skipped in the last seven days etc,were associated with the time of survival in patients after the initiation of ART. Patients who had been taking CTX at ART initiation were at lower risk of death (adjusted HR=0.71,95%CI:0.63-0.80;P=0.00),compared to those who had never taken the CTX. Conclusion The co-trimoxazole prophylaxis program was associated with the reduced mortality among AIDS patients who were on ART in Henan province,especially during the first year.

Effect of co-trimoxazole prophylaxis used for AIDS patients under anti-retroviral therapy / 中华流行病学杂志

Objective To analyze the situation of survival among AIDS patients under co-trimoxazole prophylaxis as initial anti-retroviral therapy(ART),in Henan province during 2007-2011. Methods Information on AIDS patients receiving initial ART during 2007-2011 was collected from the Chinese HIV/AIDS Integrated Control System. Kaplan-Meier estimation was used to generate survival curves,and Cox proportional hazard regression model was used to determine associated factors of survival status. According to the previous CTX use before ART,the subjects were divided into 3 groups including who had never taken CTX,who had taken CTX and still taking now,who had taken CTX and not current taking. Results A total of 13 103 eligible AIDS patients were identified. 1 702 patients died within 6 years after the initiation of ART,with the mortality as 4.46/100 person year. Among the 455 patients who died within 3 months and 970 died within 12 months,the mortality rates were 14.15/100 person year and 7.78/100 person year,respectively. The Kaplan-Meier survival curves showed that the survival time and mortality of the patients who had taken CTX was longer AND lower than those patients who had never taken CTX when starting the ART program. Results from the log-rank test showed that the difference of two groups was statistically significant during 12 months after the ART(log-rank=5.15,P=0.02). After controlling for other variables,results from multivariable analysis of COX model showed that factors as age,gender,marital status,perion between confirmed diagnosis and receiving the ART,baseline CD4+T cells count,clinical stage,initial therapy schedule,date when starting the ART,number of symptoms at baseline,use of CTX before starting the ART and ART being skipped in the last seven days etc,were associated with the time of survival in patients after the initiation of ART. Patients who had been taking CTX at ART initiation were at lower risk of death (adjusted HR=0.71,95%CI:0.63-0.80;P=0.00),compared to those who had never taken the CTX. Conclusion The co-trimoxazole prophylaxis program was associated with the reduced mortality among AIDS patients who were on ART in Henan province,especially during the first year.

Antimicrobial susceptibility of Salmonella enterica serovars in a tertiary care hospital in southern India.

Background & objectives: Salmonella enterica serovars Typhi and Paratyphi are predominantly known to cause enteric fever. Multidrug resistance in S. Tphi and S. Paratyphi has emerged as a cause of concern. This study was done to evaluate status in antimicrobial susceptibility patterns of Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi obtained from blood culture in a tertiary care hospital in south India. Methods: Blood isolates of Salmonella species over a two year period between May 2009 and June 2011 were studied. A total of 322 isolates of Salmonella species were tested for antimicrobial susceptibility by Kirby-Bauer disc diffusion method. The MIC of ciprofloxacin was obtained by E-test, and azithromycin MIC was confirmed by agar dilution method for a limited number of isolates. Results: Of the total of 322 isolates studied, 186 (57.8%) were S. Typhi, 134 (41.6%) were S. Paratyphi A, and two were S. Paratyphi B. Of these, 44(13.66%) were resistant to ciprofloxacin (MIC <0.50 μg/ml) and 296 (91.9%) were nalidixic acid resistant. Of these 296 nalidixic acid resistant isolates, 278 (94%) were susceptible to ciprofloxacin by MIC criteria (<0.5 μg/ml). Of the 262 isolates tested for azithromycin sensitivity, only 120 (46%) were susceptible, whereas 81 (31%) were resistant and 55 (21%) showed intermediate susceptibility. Of the isolates, 322 (90%) were susceptible to ampicillin and (95%) were susceptible to co-trimoxazole. However, all the isolates were susceptible to chloramphenicol and ceftriaxone. Interpretation & conclusions: Nalidixic acid resistance screening is not a reliable surrogate indicator of ciprofloxacin resistance. Ciprofloxacin MIC should to be routinely done. Azithromycin resistance appears to be emerging. However, isolates showed a high degree of susceptibility to ampicillin, co-trimoxazole and chloramphenicol. Thus, antibiotics like ampicillin and co-trimoxazole may once again be useful for the management of enteric fever in southern India.

Co-trimoxazole induced Stevens-Johnson syndrome in pediatric age group.

Stevens-Johnson syndrome (SJS) is a serious dermatological disorder commonly caused as idiosyncratic reaction to drugs, the most common ones being antibiotics, anticonvulsants and non-steroidal anti-inflammatory drugs. Here, we report a case of co-trimoxazole induced SJS in a 2 years old male child.

An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

Background: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied. Aim: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population. Methods: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. Results: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively Conclusions: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.

Cotrimoxazole enhances the in vitro susceptibility of Coccidioides posadasii to antifungals

The aim of the present study was to evaluate the effect of cotrimoxazole on the in vitro susceptibility of Coccidioides posadasii strains to antifungals. A total of 18 strains of C. posadasii isolated in Brazil were evaluated in this study. The assays were performed in accordance with the Clinical and Laboratory Standards Institute guidelines and the combinations were tested using the checkerboard method. The minimum inhibitory concentrations were reduced by 11, 2.4, 4.3 and 3.5 times for amphotericin B, itraconazole, fluconazole and voriconazole, respectively. Moreover, it was seen that cotrimoxazole itself inhibited C. posadasii strains in vitro. The impairment of folic acid synthesis may be a potential antifungal target for C. posadasii.

Cutaneous adverse reactions to sulfonamide antibiotics.

Background: Sulfonamides are divided into two main groups which are sulfonamide antibiotics and sulfonamide non-antibiotics. The wide use of sulfonamide antibiotics leads to increasing incidence of sulfonamide cutaneous reactions. Objective: The purpose of this study is to explore the cutaneous manifestations induced by sulfonamide antibiotics in a large number of Thai patients, including human immunodeficiency virus (HIV) and non-HIV infected individuals. The second purpose is to determine the risk factors for development of sulfonamide cutaneous reactions. Methods: We retrospectively studied 191 patients with sulfonamide antibiotics cutaneous reactions attending the adverse drug reaction center, Siriraj Hospital, Bangkok between 2006 and 2010. Results: Majority of the patients was female (59.7%).Maculopapular rash was the most common cutaneous manifestation (37.7%), followed by fixed drug eruption (22%), angioedema with or without urticaria (12.6%) and urticaria alone (12%). Among those with known HIV serology, maculopapular eruption occurred more frequently in the HIV positive group while fixed drug eruption occurred more frequently in HIV-negative group. Conclusion: From our study, there were no significant determination factors to develop serious drug reactions. However, the HIV-positive status and lower level of CD4 count had a tendency to increase risk of developing serious cutaneous reactions.

Sporotrichoid nocardiosis with cutaneous dissemination.

Dissemination of primary cutaneous nocardiosis is a rare event. A 37-year-old man working as farmer presented with multiple painful suppurative nodular and ulcerative skin lesions over left lower extremities, in a linear pattern, with duration of five months and single painful nodule over right elbow since last three months. We found the presence of beaded filamentous bacteria in Gram stain smear and partial acid fast stain, from the smear taken from pus. Patient responded well to cotrimoxazole therapy. Hence, we confirm our diagnosis of sporotrichoid pattern of cutaneous nocardiosis with dissemination to other cutaneous area.

Severe adverse cutaneous drug reactions: The 5 year Kuala Lumpur Hospital experience

Introduction: Stevens Johnson syndrome (SJS), Stevens Johnson Syndrome - toxic epidermal necrolysis overlap syndrome (SJS-TEN overlap), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DHS) are well known severe adverse cutaneous drug reactions (SACDRs). All clinicians are responsible for the diagnosis and management of SACDR. Objective: To retrospectively review the clinical patterns, management strategies and outcome of 134 patients with severe adverse cutaneous drug reactions managed at the Department of Dermatology, Kuala Lumpur Hospital between 2006 and 2010. Results: The mean age of presentation was 44.8 years (13-83). The male: female ratio was 1:1. There were 68 cases (50.7%) of SJS, 10 cases (7.5%) SJS-TEN overlap, 32 cases (23.9%) TEN and 24 cases (17.9%) DHS. The five commonest drugs associated with SACDRs were allopurinol (26.9%), carbamazepine (13.4%), phenytoin (9.7%), non-steroidal anti-inflammatory drugs (11.2%) and co-trimoxazole (7.5%). The mean duration of drug exposure before the onset of reaction was 2.8 weeks. A hundred and thirty patients (97%) were managed as in-patient. The mean duration of in-patient stay was 12.4 days. All identified culprit drugs were withheld. Systemic corticosteroids was given to 96% cases of DHS with mean duration of 9.7 weeks; 52.9% of SJS with mean duration of 2.8 weeks; 60% of SJS-TEN overlap with mean duration of 2.3 weeks; and 62.5% of TEN with mean duration of 3.3 weeks. Thirteen patients (42%) with TEN were treated with intravenous immunoglobulin. Eight patients (6%) died, of which 7 were TEN and one DHS. Conclusion: SACDRs are life-threatening emergencies which not only results in significant morbidity and mortality; but also potentially increases the health care cost and burden. Clinicians should recognize high risk medications and prescribe them with great caution.