Presumed Bacterial Infection Research Articles

Switch Therapy in Full-Term Neonates with Presumed or Proven Bacterial Infection

This case-control study of full-term newborns with presumed or proven bacterial infection compared the efficacy, safety and tolerability of switch antibiotic therapy and traditional completely intravenous antibiotic administration. There were 36 newborns treated with switch therapy (i.v. ampicillin + sulbactam combined with i.v. amikacin for 3 days followed by oral cefpodoxime proxetil for 5 days); there were 72 full-term new-borns with the same characteristics as controls who received i.v. ampicillin + sulbac-tam combined with i.v. amikacin for 3 days followed by i.v. ampicillin + sulbactam alone for a further 5 days. The results showed that full-term newborns with presumed or proven bacterial infection initially treated with intravenous antibiotics can be switched to oral antibiotics after 3 days' therapy if physical and laboratory data indicate the disappearance of infection, thus significantly reducing the length of stay in the neonatal intensive care unit and significantly increasing breastfeeding, without having any negative clinical impact.

Urogenital tuberculosis in a patient with AIDS: an unusual presentation

A 38-year-old man with AIDS presented to hospital with a 3-month history of fevers, bilateral lumbar pain, dysuria and increased urinary frequency. Six years earlier he had received 6 months' treatment for pulmonary tuberculosis. At presentation, he was on antiretroviral therapy with a combination of efavirenz, stavudine and lamivudine. Physical examination, evaluation of HIV viral load, CD4 count, measurement of serum hemoglobin concentration, white blood cell count, urinalysis, urine culture for usual pathogens, direct smear and urine culture for Mycobacterium tuberculosis, chest radiography, abdominal CT, measurement of serum creatinine concentration and estimated creatinine clearance. Urogenital tuberculosis. The patient's symptoms and radiological abnormalities persisted despite antibiotic therapy for presumed bacterial infection. After urine culture had confirmed M. tuberculosis infection, he was administered pharmacological treatment comprising isoniazid, rifampin, pyrazinamide and ethambutol for 2 months, with isoniazid and rifampin given for a further 7 months. His symptoms improved within a few days of initiating treatment. Six months after treatment started, CT revealed a nonfunctioning right kidney and a functional left kidney with areas of scarring. The patient refused right nephrectomy, and completed his pharmacological treatment. No evidence of disease recurrence was observed during 2 years of follow-up.

World Health Organization Clinical Stage 3 disease conditions in HIV-infected patients who start antiretroviral therapy in Malawi

There is little information about disease conditions that are diagnosed in patients diagnosed as having World Health Organization Clinical Stage 3 HIV who are started on antiretroviral therapy (ART) in Africa. We therefore conducted an audit in the central region of Malawi of patients registered for ART between January and September 2006. There were 4299 patients in Stage 3 of whom 4154 had data about their disease conditions. Only one condition was listed for 3880 patients. Of these, 1892 (48.8%) had unexplained weight loss, chronic fever or chronic diarrhoea, 822 (21.2%) had active/previous tuberculosis (TB) and 671 (17.3%) had a severe presumed bacterial infection. No patient was diagnosed as having haematological abnormalities. Nearly half the patients started on ART had a symptomatic, unspecified disease, (which may be obscuring important pathologies such as TB) and almost no laboratory assessment had taken place before the commencement of ART. These two areas need to be addressed in order to improve the management of patients starting on ART.

Cytomegalovirus Ulcer

A 47-year-old man with multiple-drug–resistant AIDS was admitted to Yale–New Haven Hospital for evaluation of mental status and neuromotor changes and a 6-week history of a painful, nonhealing, enlarging ulcer on the lower extremity that the patient attributed to minor trauma. The patient had received outpatient wound care and several courses of oral antibiotics, but he was taking neither antiretroviral medications nor prophylaxis for opportunistic infections. The patient’s most recent CD4 cell count was less than 20/μL with a viral load of 715000 copies/mL. He had a history of successfully treated cytomegalovirus (CMV) retinitis and Pneumocystis carinii pneumonia. On admission, he displayed clinical and radiologic features consistent with cerebral toxoplasmosis. He had no history of diabetes mellitus, peripheral vascular disease, or neuropathic disease. During his hospital stay, the patient received intravenous and oral antibiotics (ampicillin sodium– sulbactam sodium, aztreonam, and clindamycin) for presumed bacterial infection of the ulcer, and a skin care nurse treated the wound daily with bacitracin zinc and dry dressings. After 4 days in the hospital with no improvement, dermatology consultation was requested. On physical examination, there was a tender 3.0 2.0-cm ulcer on the right lateral part of the heel with surrounding erythema and induration (Figure 1). The border was well demarcated and not elevated, undermined, or scalloped. The base contained granulation tissue and necrotic debris. The patient had no oral, ocular, or anogenital ulcers. The remainder of the lower extremity examination was significant for 1+ pitting ankle edema, adequate capillary refill time, palpable dorsalis pedis pulses, and no evidence of compromised circulation or peripheral neuropathy. The patient also had molluscum contagiosum on his chest. A punch biopsy specimen from the edge of the ulcer showed hyperplastic epidermis and numerous thickwalled blood vessels in the dermis, as well as a perivascular lymphocytic infiltrate. Among normal endothelial cells were many large, irregularly shaped endothelial cells with large basophilic intranuclear inclusions, in some cells surrounded by clear halos. Intracytoplasmic basophilic inclusions were also present (Figure 2). Immunohistochemical studies showed CMV antigen reactivity within the endothelial cells. Direct immu-

Outcomes after judicious antibiotic use for respiratory tract infections seen in a private pediatric practice.

Most respiratory tract infections (RTIs) in children have a viral cause, they resolve on their own, and antibiotics need not be prescribed. We sought to provide evidence that judicious antibiotic use can be accomplished in private pediatric practice without observing an increase in return office visits or in the rate of bacterial infections that may follow. This was a prospective 12-month study from July 1, 1996 through June 30, 1997. On the same 1 day each week, a representative convenience sample of acute respiratory tract illness patients was enrolled, and laboratory studies performed as appropriate, including viral cultures on all. Children were then followed for 30 days to ascertain the outcomes of not prescribing antibiotics except when specific bacterial infections were present at the initial visit. Three hundred eighty-three children were enrolled; 293 (77%) did not receive antibiotics at the enrollment visit. Ninety children (23%) received antibiotics based on a diagnosis of acute otitis media (n = 53), acute streptococcal tonsillopharyngitis (n = 18), or other presumed or documented bacterial infections (n = 19). An unscheduled return visit related to the initial visit occurred for 86 (29%) of the 293 children not receiving antibiotics initially and in 40 (44%) of 90 children receiving antibiotics initially. Eighty-seven children (23%) had positive viral culture results. The most frequently isolated viruses were adenovirus, enterovirus, parainfluenzae virus, and influenza virus. Children with RTIs without a concomitant presumed or proven bacterial infection do not require antibiotics. In this busy office practice, >75% of the children presenting with an RTI did not have a presumed or proven bacterial infection. These children did not have a higher rate of return office visits or an increase in bacterial infections. This reinforces the judicious use of antibiotics in managing children with RTIs.outcomes, antibiotic, respiratory infections.

Bacterial infections in infants 60 days and younger: epidemiology, resistance, and implications for treatment.

To establish what might be more optimal initial antibiotic therapy for suspected invasive bacterial infections in infants 60 days or younger who are evaluated in the emergency department (ED). Urban university-affiliated pediatric referral center with an average yearly ED census of 52000 visits during the study period. We assembled a retrospective case series of all positive blood, urine, and cerebrospinal fluid cultures in children 60 days or younger from January 1, 1994, through December 31, 1997, obtained from both inpatients and patients initially evaluated in the ED. From this case series we determined the frequency of bacterial pathogens responsible for such infections in this age group. Pathogens were defined as group B streptococcus, various enteric gram-negative rods (GNRs), Listeria monocytogenes, enterococcus, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type B, and Staphylococcus aureus. A subgroup analysis was performed to determine resistance patterns among the GNRs isolated from patients evaluated in the ED. A total of 367 pathogens were isolated: 187 (51.0%) in the neonatal intensive care unit, 153 (41.7%) in the ED, 20 (5.4%) in the inpatient wards, and 7 (1.9%) in the pediatric intensive care unit. Of the 121 pathogens isolated from 120 ED patients that were eligible for review, 94 (77.7%) were in the urine only, 16 (13.2%) in blood only, 4 (3.3%) in cerebrospinal fluid only, 3 (2.5%) in blood and cerebrospinal fluid, and 4 (3.3%) in blood and urine. Organisms isolated included GNRs (n = 96, 79.3%), group B streptococcus (n = 14, 11.6%), enterococcus (n = 7, 5.8%), S. pneumoniae (n = 3, 2.5%), and N. meningitidis (n = 1, 0.8%). No Listeria were isolated. Of the 96 GNRs isolated, 60 (62.5%; 95% confidence interval, 52.8%-72.1%) were ampicillin resistant. All were sensitive to gentamicin sulfate and cefotaxime sodium. Our results reveal 2 important facts: (1) during a 4-year period, no isolates of Listeria were identified from any patients 60 days or younger; and (2) of the 96 GNRs isolated from patients in the ED, more than 60% were ampicillin resistant. These data suggest that in similar centers with a low incidence of infection with Listeria and high levels of ampicillin resistance among GNRs, empiric use of ampicillin as part of a combination for presumed bacterial infections in patients 60 days or younger initially evaluated in the ED may be neither necessary nor beneficial. Consideration should be given to empiric initial antibiotic therapy using a third-generation cephalosporin with or without gentamicin.

Original Paper: Treatment of respiratory tract infections - a study in 18 general practices in Germany

Background: Respiratory tract infections are common in general practice: antibiotics and symptomatic drugs are frequently prescribed for these conditions. Since most respiratory tract infections are of viral origin, there is no conclusive evidence of usefulness of such medication. The reasons for general practitioners' (GPs') prescribing behaviour are not well understood.Objective: To assess the influence of medical and nonmedical factors on antibiotic and symptomatic drug prescription for respiratory tract infections: the common cold, sinusitis, tonsillitis, laryngitis and bronchitis.Methods: Eighteen GPs recruited all the adult patients (maximum n=30) who consulted them with symptoms of respiratory tract infection during a two-week period. Information on patients was obtained from matched physician-patient questionnaires completed for each patient, or in case of non-responding patients, from the GP questionnaire only. The patient forms focused on symptoms, reasons for consulting and expectations; whereas the physician documentation concentrated on diagnosis, prescriptions and pre-existing chronic conditions. The predictors of antibiotic and symptomatic drug prescriptions were identified by univariate and multivariate analyses.Results: A total of 417 physician questionnaires including 280 matched doctor-patient questionnaires were obtained, 35 GP cases (27 matched pairs) were excluded from the analysis because of a principal diagnosis other than a respiratory tract infection.Antibiotics were prescribed for 106 of 382 patients (27.7%); and cough and cold preparations for 67%. Tonsillitis (odds ratio [OR]: 216.65), bronchitis (OR: 3.44), sinusitis (OR: 2.48) and yellow-green sputum (OR: 4.44) and not being a current smoker (OR: 0.2) significantly predicted antibiotic prescriptions.Patients' wish for a symptomatic drug (OR: 18.84), bronchitis (OR: 3.43), yellow-green sputum (OR: 2.34) and not having tonsillitis (OR: 0.10) predicted prescription of symptomatic drugs.Conclusion: The diagnosis of a presumed bacterial infection is important for a GP's decision to prescribe antibiotics, even though many of these patients probably have a viral disease. Patient expectations are extremely important when prescribing cough and cold drugs. For a better understanding of GPs' prescribing behaviour, a simultaneous consideration of medical and non-medical factors seems appropriate.

Antibiotic Stewardship in a Paediatric Hospital

Infectious diseases comprise a major percentage of paediatric illnesses as infections in out-patients, illnesses requiring hospitalization for treatment and nosocomially acquired infections. Although a significant percentage of infectious diseases are of viral etiology, initial empirical therapy for febrile undiagnosed illnesses and for presumed or proven bacterial infections results in widespread use of antimicrobials. In contrast to the beneficial effects of antibiotics are their expense, their adverse effects and their contribution to the emergence of increasingly drug-resistant organisms. Strategies to enhance the appropriate use of antimicrobials are most evident in hospitals such as The Hospital for Sick Children – a tertiary care paediatric hospital whose infrastructure supports and encourages proper use. The use of many of the following strategies (1) has been shown to reduce drug expenditures and overall hospital costs by improving patient care.

Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock.

To test the hypothesis that variations in oxygen consumption (VO2) and resting metabolic rate reflect the severity of bacterial infections and reflect the development of sepsis syndrome and septic shock. Observational study with sequential measurements of VO2 and resting metabolic rate by expiratory gas analysis. Medical intensive care unit. Thirty patients, treated primarily for presumed bacterial infection, were examined on 118 treatment days. None. VO2 and resting metabolic rate were measured by expiratory gas analysis. For mechanically ventilated patients, a measurement system was developed, based on a paramagnetic oxygen sensor, an infrared CO2 sensor, and digital signal averaging. Measurements in spontaneously breathing patients were performed with a metabolic monitor. Patients were assigned by clinical criteria to the following groups: sepsis, sepsis syndrome, and septic shock. The lowest VO2 value of each patient in each stage was evaluated. Mean VO2 in 15 patients with sepsis was 180 +/- 19 (SD) mL/min/m2, in 11 patients with sepsis syndrome 156 +/- 22 mL/min/m2, and in eight patients with septic shock 120 +/- 27 mL/min/m2 (p < .001). Mean resting metabolic rate in sepsis was +55 +/- 14%, in sepsis syndrome +24 +/- 12%, and in septic shock +2 +/- 24% (p < .001). Mean oxygen delivery (DO2) was 501 +/- 116 mL/min/m2 in sepsis, 515 +/- 186 mL/min/m2 in sepsis syndrome, and 404 +/- 96 mL/min/m2 in septic shock. Oxygen extraction (VO2/DO2) was highest in sepsis (0.39 vs. 0.33 in sepsis syndrome and 0.29 in septic shock). During recovery from sepsis syndrome or septic shock, a significant increase in resting metabolic rate to +61 +/- 22% was measured in nine patients. In sepsis syndrome, VO2 and resting metabolic rate are enhanced by 30% compared with normal basal metabolism, but they are markedly reduced compared with uncomplicated sepsis. The higher VO2 in uncomplicated sepsis is flow independent. The noninvasive measurement of VO2 and resting metabolic rate by expiratory gas analysis therefore can be used as a quantitative staging and monitoring parameter for the development of sepsis syndrome and septic shock.

Relationship between cefpirome clearance, serum creatinine, weight and age in patients treated for infection

Cefpirome serum concentrations were measured by microbiological assay in 30 patients after five to nine days of treatment with 1 or 2 g bd for moderate to severe infection of presumed bacterial origin. Patients with serum creatinine (SCr) greater than 220 mumol/L were excluded. The age of patients ranged from 34-86 years. Creatinine clearance (Clcr) was calculated from age, sex, weight and SCr. The range of SCr was 63-220 mumol/L and the range of Clcr was 18-169 mL/min. The correlation coefficient with cefpirome clearance was 0.464 for SCr and 0.747 for Clcr. More than half of the patients with Clcr less than 50 mL/min had SCr within the normal range of 70-150 mumol/L. Mean cefpirome clearance in patients with Clcr 18-50 mL/min was 42.7 mL/min, which is very similar to the figure of 43.5 mL/min reported in a single dose volunteer study in patients with renal failure. Mean cefpirome clearance in patients with Clcr greater than 80 mL/min was 107.6 mL/min. In conclusion, these data on cefpirome clearance obtained after multiple dose treatment of patients with presumed bacterial infection are consistent with data previously obtained from single dose volunteer studies and support the currently recommended dose regimens. Clinicians should take account of age, weight and sex when estimating renal function from SCr.

Urinary Tract Infections in Febrile Infants Younger Than 8 Weeks of Age

In this prospective study of 442 infants younger than 8 weeks of age who attended a pediatric emergency department with temperature greater than or equal to 100.6 degrees F (38.1 degrees C), urinary tract infections (UTIs) were found in 33 patients (7.5%), 2 of whom were bacteremic. Clinical and laboratory data were not helpful for identifying UTIs. Of the 33 patients with UTIs, 32 had urinalyses recorded; 16 were suggestive of a UTI (more than five white blood cells per high-power field or any bacteria present). Of the 16 infants with apparently normal urinalysis results, three had an emergency department diagnosis suggesting an alternative bacterial focus of infection. If the physician had decided on the basis of apparently normal urinalysis results to forgo obtaining a urine culture, more than half of the UTIs would have been missed. Bag-collected specimens were significantly more likely to yield indeterminate urine culture results than either catheter or suprapubic specimens. In addition, uncircumcised males were significantly more likely to have a UTI than circumcised boys. These results suggest that a suprapubic or catheter-obtained urine specimen for culture is a necessary part of the evaluation of all febrile infants younger than 8 weeks of age, regardless of the urinalysis findings or another focus of presumed bacterial infection.

Intravenous sulbactam/ampicillin in the treatment of pediatric infections

A total of 82 patients involving 83 episodes of proven or presumed bacterial infection were treated with sulbactam/ampicillin. These included 36 cases of soft tissue infection or abscess, four cases of joint or bone infection, 20 cases of respiratory tract infection (17 cases of pneumonia, two of otitis media, and one of tonsillitis), 15 urinary tract infections, three cases of enterocolitis, one case of infective endocarditis, two cases of septicemia, and two of peritonitis. The causative pathogen was isolated in 48 cases (49 infections). These pathogens included Staphylococcus aureus 13 cases, Staphylococcus epidermidis one, Streptococcus pyogenes two, Streptococcus pneumoniae two, Viridans group streptococcus two, peptostreptococcus one, Haemophilus influenzae one, Escherichia coli 12, Enterobacter cloacae three, Proteus mirabilis one, Acinetobacter calcoaceticus one, Salmonella spp. two, Shigella sonnei one, Bacteroides fragilis one, and polymicrobial infections of various combinations in five cases. No bacterial pathogens were isolated in 34 infections, 14 cases of pneumonia and 15 soft tissue infections. Sulbactam/ampicillin was given by intravenous bolus in a dosage range of 75–450 mg/kg/day in four divided doses for variable periods of time depending on the type and severity of the infection. Of a total of 83 episodes of infections, 80 (96.4%) cases were either cured or improved. Bacteriologic eradication also occurred in 46 (93.9%) of 49 infections. Side effects were diarrhea in two patients, acute hemolytic anemia in one patient, and transient elevations in SGOT and leukopenia in one patient. Side effects disappeared upon completion of treatment. Sulbactam/ampicillin is a safe and effective antibiotic for the treatment of common pediatric infections.

Bacterial Meningitis in the Elderly-Reply

—Dr Harris focuses on specific clinical characteristics of our older adult population (age, ≥50 years) and reiterates concerns regarding efficacy of third-generation cephalosporins in the treatment of gramnegative bacillary meningitis. 1 It is important to differentiate those patients with microbiologically proved bacterial meningitis from those with presumed bacterial infections treated as such. In the latter group, situations associated with a negative bacterial culture included prior antibiotic treatment, parameningeal focus of infection, and CSF leak due to prior trauma or neurosurgical procedure. While higher mortality correlated with positive microbiologie diagnosis in our series of patients,1 characteristics (eg, preexisting neurologic disease, previous neurologic surgical procedures, change in sensorium at time of presentation, and community onset vs hospital onset) did not differ significantly between these two subgroups (Table 1). The eight patients with aseptic meningitis had no preexisting neurologic disease or neurologic surgical procedures, and all had community-acquired infection. The mean CSF white blood cell

C-reactive protein and zeta sedimentation ratio as indicators of bacteremia in pediatric patients

RECENT STUDIES have examined the usefulness of history and observation variables, ~: slide-agglutination C-reactive protein, 6 erythrocyte sedimentation rate, ~ and a variety of white blood cell measures *~ in identifying children with bacteremia or invasive bacterial infections. Although all of these tests have shown a significant association with presumed bacterial infection, none has proved sensitive enough to be used as a single measure, and certain of the tests have practical drawbacks. We examined the zeta sedimentation ratio and quantitative C-reactive protein, two recently developed tests that are potentially advantageous in that they can be performed rapidly and require small amounts of blood. Our study was designed to evaluate their utility in screening for bacteremia, a condition that can for study purposes be rigorously and objectively defined. The potential association of bacteremia with serious complications 9-~'also makes this condition a bottom line consideration in the evaluation of febrile infants and young children.

THE DETECTION OF GROUP B STREPTOCOCCAL POLYSACCHARIDES IN URINE BY AGGLUTINATION

Prepared staphylococcal co-agglutination reagents were used for the detection of group B streptococcal polysaccharides in the concentrated and unconcentrated urine of 78 infants with presumed bacterial infection. These prepared reagents were compared to commerically available reagents (Phadebact, Wellcogen). All reagents were evaluated for their ability to identify patients infected with group B streptococci and for their ability to detect purified group B and type III polysaccharides. All three reagents were able to identify the six patients with positive group B streptococcal blood cultures when concentrated urine was tested. All three reagents had equivalent levels (62.5 ng/ml) of detection for the group B polysaccharide when 20 ul of polysaccharide solution was used. These reagents had poor levels of detection for the type III polysaccharide. Prepared reagents were as sensitive as those commercially available for the detection of infants with group B streptococcal disease and were one one-hundredth the cost.

Tobramycin and clindamycin in the treatment of febrile leukaemic patients.

Thirty-nine episodes of presumed or proven bacterial infection were treated in 22 adult patients with leukaemia, using a combination of tobramycin and clindamycin. In 5 patients who had not responded within 72 h, co-trimoxazole was successful. Fifteen out of 16 (94%) cases with proven infection recovered as did all 14 with presumed infection. The commonest infecting organism was Escherichia coli but Pseudomonas aeruginosa was only encountered in 1 patient. Superinfection with Candida albicans caused the deaths of 3 patients. One patient died of pneumonia complicated by renal failure. There were no other serious side effects of this combination of antibiotics. The high recovery rate is considered to be due to the early use of broad spectrum antibiotics in pyrexial leukaemic patients and was achieved without special isolation facilities, prophylactic antimicrobial therapy or leucocyte transfusions.

Use of the nitroblue tetrazolium dye test. An aid in managing patients with cystic fibrosis.

One hundred fifty-seven nitroblue tetrazolium (NBT) dye tests were performed on 78 patients with cystic fibrosis. A positive NBT response of >10% was significantly correlated with the presence of presumed bacterial respiratory infection, and stable patients had normal NBT scores below 10%. Serial determinations in 16 instances of bacterial infection were helpful in evaluating response to therapy. Total leukocyte count, mean percentage of immature polymorphonuclear leukocytes, temperature, or a change in sputum flora were not helpful in detecting bacterial infection in these patients. The NBT test is a valuable adjunct in the surveillance of patients with cystic fibrosis.

Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia.

Seventy-five acutely ill, febrile patients with cancer and granulocytopenia were treated empirically with a combination of carbenicillin and gentamicin for presumed bacterial infection. Cultures taken before the initiation of antibiotics subsequently documented the presence of infection in 48 of these patients, of whom 21 were shown to have Pseudomonas aeruginosa infections. Fourteen of these patients with pseudomonas infections had complete improvement, three improved temporarily but later died of infection, two had no improvement, and two could not be evaluated. This antibiotic combination was less promising for the infections caused by other gram-negative bacteria, especially klebsiella. Superinfection occurred in eight patients. Combination carbenicillin and gentamicin is of value as initial antibiotic therapy for suspected Ps. aeruginosa infection in granulocytopenic patients with cancer but only after careful examination and extensive culturing.