Extended follow-up of an antibiotic cycling program for the management of febrile neutropenia in a hematologic malignancy and hematopoietic cell transplantation unit.

BACKGROUND: Febrile neutropenia is a common complication during treatment of hematological malignancies and hematopoietic cell transplantation. Empiric antibiotic therapy in this setting, while standard of care, commonly leads to microbial resistance. We have previously shown that cycling antibiotics in this patient population is feasible. This report provides long-term follow-up of cycling antibiotics in this patient population. METHODS: In a prospective cohort of hematological malignancy patients with neutropenic fever, we sought to evaluate the role of empiric antibiotic cycling in preventing antibiotic resistance. Antibiotic cycling was initiated in March 2002 and, until June 2005, antibiotics were cycled every 8 months (Cycling Period A). From July 2005 to December 2009, antibiotics were cycled every 3 months (Cycling Period B). The rates of bacteremia, resistance, and complications were compared to a retrospective cohort (Pre-cycling Period). RESULTS: The rate of gram-negative bacteremia decreased when compared to Cycling Periods A and B (5.3 vs. 2.1 and 3.3 episodes/1000 patient-days, respectively, P < 0.0001), most likely owing to implementation of quinolone prophylaxis. The resistance profile of the gram-negative organisms isolated remained stable over the 3 time periods, with the exception of an increase in quinolone resistance during the cycling periods. Gram-positive bacteremia rates remained stable, but vancomycin-resistant Enterococcus (VRE) increased significantly (0.1 vs. 1.0 and 1.6 episodes/1000 patient-days, respectively, P = 0.005) during cycling periods. Mortality rates were comparable. CONCLUSIONS: Antibiotic cycling for neutropenic fever was effectively implemented and followed over an extended time period. Gram-negative resistance remained stable, but there is some concern for selection of resistant gram-positive bacteria, specifically VRE. Although antibiotic cycling did not seem to cause resistance in our study, further study is necessary to clarify the effect of cycling on antibiotic resistance, patient outcomes, and hospital cost.

Culture-confirmed typhoid fever and pregnancy.

BACKGROUND: The relationship between pregnancy and typhoid fever is not well defined. The objective of this study was twofold: to assess the effect of the pregnant and postpartum host on typhoid disease expression, and to explore the relationship between typhoid fever and pregnancy outcome. METHODS: Over an 11-year period, all 181 adult women with blood culture-confirmed typhoid fever admitted to a university hospital in Karachi, Pakistan were studied; those with pregnancy-related disease were compared to the non-pregnant women. The relationship between typhoid fever and pregnancy outcome was evaluated by comparing 80 pregnant women with typhoid, with 194 randomly selected pregnant women without typhoid who were matched for age and study year. RESULTS: In adult females with bacteremic typhoid disease, a significant proportion was pregnancy-related (47%). These women were less likely to have other co-morbid illnesses (2% vs. 27%, p<0.001) and were almost exclusively treated with ampicillin/amoxicillin or third-generation cephalosporins, while the non-pregnant women with typhoid fever preferentially received quinolones. The mean duration of antimicrobial therapy was similar in both groups (14 days) but the non-pregnant group defervesced earlier (4.2 days vs. 5.6 days, p=0.011). Complications of typhoid fever were significantly more likely in the non-pregnant group (23% vs. 8%, p=0.005) and primarily involved lower gastrointestinal bleeding. On comparing the pregnant women with typhoid with randomly selected age-matched pregnant women without typhoid, there were no apparent effects of typhoid fever on pregnancy outcome as measured by gestational age at delivery, pregnancy complications, modes of delivery, neonate gender, birth weight, or birth Apgar scores. CONCLUSIONS: While pregnancy is a risk factor for and effects typhoid disease expression, typhoid fever does not appear to affect pregnancy outcome.

The clinical impact of antibacterial prophylaxis and cycling antibiotics for febrile neutropenia in a hematological malignancy and transplantation unit.

Febrile neutropenia is an expected complication during treatment of aggressive hematological malignancies and hematopoietic cell transplantation. We conducted a prospective cohort trial to determine the effects and safety of prophylactic fluoroquinolone administration, and rotation of empiric antibiotics for neutropenic fever in this patient population. From March 2002 through 2004, patients were treated with prophylactic levofloxacin during prolonged neutropenia, and a cycling schedule of empiric antibiotic therapy for neutropenic fever was initiated. The rates of bacteremia, resistance and complications were compared to a retrospective cohort of previously treated patients. The rate of gram-negative bacteremia decreased after the initiation of prophylactic levofloxacin (4.7 vs 1.8 episodes/1000 patient days, P<0.05). Gram-positive bacteremia rates remained unchanged, but more isolates of Enterococcus faecium were resistant to vancomycin after the intervention began. Resistance to the antibiotic agents used in the rotation did not emerge. There was no change in mortality during the intervention period. A prophylactic and cycling antibiotic schedule was successfully implemented on a hematological malignancy and hematopoietic cell transplant unit. gram-negative bacteremia was significantly decreased, without emergence of resistance. Concerns with Gram-positive resistance will require further observation.

Features distinguishing amoebic from pyogenic liver abscess: a review of 577 adult cases.

Distinguishing amoebic from pyogenic liver abscesses is crucial because their treatments and prognoses differ. We retrospectively reviewed the medical records of 577 adults with liver abscess in order to identify clinical, laboratory, and radiographic factors useful in differentiating these microbial aetiologies. Presumptive diagnoses of amoebic (n = 471; 82%) vs. pyogenic (n = 106; 18%) abscess were based upon amoebic serology, microbiological culture results, and response to therapy. Patients with amoebic abscess were more likely to be young males with a tender, solitary, right lobe abscess (P = 0.012). Univariate analysis found patients with pyogenic abscess more likely to be over 50 years old, with a history of diabetes and jaundice, with pulmonary findings, multiple abscesses, amoebic serology titres <1:256 IU, and lower levels of serum albumin (P < 0.04). Multivariate logistic regression analysis confirmed that age >50 years, pulmonary findings on examination, multiple abscesses, and amebic serology titres <1:256 IU were predictive of pyogenic infection. Several clinical and laboratory parameters can aid in the differentiation of amebic and pyogenic liver abscess. In our setting, amebic abscess is more prevalent and, in most circumstances, can be identified and managed without percutaneous aspiration.

Predictors of inpatient mortality in 190 adult patients with tuberculous meningitis.

INTRODUCTION: Tuberculous meningitis (TBM), a tuberculous infection of the leptomeninges, carries significant morbidity and mortality. To date, little literature is available regarding TBM in Pakistan. METHODS: All adult patients with TBM admitted to a tertiary care teaching hospital in Karachi, were reviewed retrospectively. AIMS: To describe the demographic profile, clinical features, laboratory and radiological picture of these patients and to identify predictors of mortality. RESULTS: Among the 190 patients analyzed, majority (28%) were between 21-30 years of age. Fever (90%), impaired consciousness (63%) and nausea/vomiting (50%) were the most common presenting symptoms. Thirty four percent were categorized as clinical stage III. CSF cultures were positive in only 5%. Thirty seven percent had an associated lung pathology on a chest X-ray. Neuroimaging revealed meningeal enhancement in 27% and hydrocephalus in 23%. All patients were treated with antituberculous therapy; 79% received concomitant steroid therapy. Neurosurgical intervention was required in 13% and mechanical ventilation support in 12%. Overall mortality was 20% and neurological sequelae were seen in 42% of the survivors. Univariate analysis showed age greater than sixty years, clinical stage III and mechanical ventilation as predictors of mortality. The logistic regression model, however, revealed that stage III presentation was not an independent predictor. CONCLUSION: We continue to see late presentations of TBM in our setting. The current study has shown that age greater than sixty years and the need for mechanical ventilation are significant independent predictors of mortality.

Predictors of mortality in brain abscess.

OBJECTIVE: Brain abscess carries significant morbidity and mortality. Our objective was to elucidate the clinical presentation of brain abscess and to assess predictors of mortality in these patients. METHODS: All patients with a brain abscess presenting to the Aga Khan University Hospital, a tertiary care referral center in Karachi, Pakistan, were studied retrospectively. Statistical analysis involved univariate analysis and a logistic regression model. RESULTS: Among the 66 patients analyzed, a distant metastatic focus of infection was the most commonly identified predisposing factor (29%). Otogenic infection was the commonest contiguous source and sinusitis was noticeably absent. Multiple abscesses were frequent (35%). Streptococci were the most common isolates (39%). Lumbar puncture was performed in 44% and steroids administered in 33%. Treatment was surgical in 58%. Most comatose patients were treated conservatively. Overall mortality was 29%. Univariate analysis identified comatose presentation and identification of a distant focus of infection as predictors of mortality. The logistic regression model, however, identified a distant focus of infection as the only independent predictor. CONCLUSION: Age greater than 30 years, corticosteroid use, multiple abscesses, performance of lumbar puncture and conservative management had no affect on outcome.

Post-coronary artery bypass surgery pericardial abscess: Salmonella paratyphi B.

Endemic enteric fever is one of the major health problems in South Asia where focal pyogenic infections with salmonella are being increasingly reported. A pericardial abscess following coronary artery bypass surgery with Salmonella paratyphi B was successfully treated, the first reported case so far.

Serotype distribution of Salmonella isolates from food animals after slaughter differs from that of isolates found in humans.

If raw meat and poultry are the primary point of entry for Salmonella species into human populations, a correlation might be expected between the serotype distribution of Salmonella species isolated from animals at the time of slaughter and that of isolates found in humans. For 1990-1996, sufficient national data were available to permit such a comparison. A mathematical model was developed to predict serotype distributions of Salmonella isolates among humans on the basis of animal data. There was a significant mismatch between the serotype distributions among humans predicted by the model and those actually observed. This mismatch raises questions about the validity of the "standard" assumptions about Salmonella transmission on which the model was based-namely, that raw animal products are the primary source for human salmonellosis, that the risk of transmission to humans is equal for all food product categories, and that all Salmonella serotypes have an equal ability to cause human illness.

Infective endocarditis and septic embolization with Ochrobactrum anthropi: case report and review of literature.

Ochrobactrum anthropi, previously known as CDC group Vd, is an aerobic, Gram-negative bacillus of low virulence that occasionally causes human infection. We describe a case of infective endocarditis with O. anthropi complicated by septic embolization. A review of all the literature reported cases of O. anthropi infection is presented and categorized into 'Central line related', 'Transplant related' and "Other pyogenic infections". Mortality appears to be related to the underlying disease state, rather than the organism.

Parasite density and malaria morbidity in the Pakistani Punjab.

The relationship between quantitative Plasmodiumfalciparum or P. vivax parasitemia and clinical illness has not been defined in Pakistan or in other areas where malaria transmission is not highly endemic. Standardized questionnaires were given to and physical examinations and parasitologic tests were performed in 8,941 subjects seen in outpatient clinics in 4 villages for 13 consecutive months in the Punjab region of Pakistan. The results, based on multivariable analysis, showed that a clinical diagnosis of malaria, a history of fever, rigors, headache, myalgia, elevated temperature, and a palpable spleen among children were all strongly associated with the presence and density of P. falciparum or P. vivax malaria in a monotonic dose-response fashion. The malaria attributable fraction of a clinical diagnosis of malaria, and the same symptoms and signs also increased with increasing P. falciparum and, to a lesser extent, P. vivax, parasitemia. Unlike in sub-Saharan Africa, clinical illness due to malaria often occurs in the Punjab among adolescents and adults and in patients with parasite densities less than 1,000/microl. Clinical guidelines based upon parasitemia and symptomatology must be adjusted according to the intensity of transmission and be specific for each geographic area.

Malaria in West Virginia: forty cases seen at West Virginia University Hospital.

In the U.S., malaria predominately occurs in travelers and immigrants. We report a series of 40 cases at West Virginia University Hospital, and 24 of whom were students who had visited areas of East Africa, West Africa and Asia usually in either December, January, August or September. Most patients (79%) reported a previous episode of malaria, and P. falciparum was identified in 60%. Fever, chills and rigors were the most common symptoms. Correct use of malaria prophylaxis was recorded in five patients, and only two of these were students. Successful outcomes were recorded in all but one patient. Our series suggests that international students would benefit from the proper use of chemoprophylaxis, thus decreasing the number of cases of malaria seen in university settings.

Prospective study on the relation between living arrangement and change in functional health status of elderly women.

Limited prospective data exist on how living arrangements are associated with change in functional health. This study evaluated whether elderly women living alone were less likely to experience functional decline when compared with women who lived with others. A total of 619 community-dwelling, white women from Baltimore, Maryland, aged 65-99 years at baseline were questioned annually from 1984 to 1986. Functional health was measured as the sum of limitations in seven physical and seven instrumental activities of daily living (Instrumental ADL). A total of 148 women experienced functional decline over the 2 years, primarily as a deterioration in Instrumental ADL. The association between living arrangement and change in Instrumental ADL depended on the level of physical impairment. Among women without severe impairment, Instrumental ADL deterioration was significantly less for those living alone compared with those living with spouses (odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.45-0.92) or nonspouse others (OR = 0.62, 95% CI 0.45-0.96). For women with severe impairment, however, those living alone had a greater decline in Instrumental ADL, especially when compared with those living with nonspouse others (OR = 5.13, 95% CI 1.23-21.28). These results suggest that, unless severely physically impaired, women living independently have less deterioration in functional health when compared with peers in alternate living arrangements.

The pharmacologic consequences of fever.

Despite its potential importance to the management of patients with febrile illnesses, the effect of fever on pharmacokinetics and pharmacodynamics has received little attention in the clinical literature. This article considers literature published in this potentially important area.