Reduction of serum albumin in non-critically ill patients during hospitalization is associated with incident hypoglycaemia.

AIM: Our study looked at the association between changes in serum albumin (SA) levels during hospitalization and incidence of hypoglycaemia among non-critically ill patients. METHODS: Included were patients discharged from internal medicine units with hospital stays ≤ 14 days. Patients were allocated to three groups: (1) admission SA > 3.5 g/dL with no decrease during hospitalization; (2) admission SA < 3.5 g/dL with no decrease during hospitalization; and (3) decrease in SA regardless of admission SA level. Incident hypoglycaemia (glucose ≤ 70 mg/dL) was predicted by applying regression analysis, using hypoglycaemia as a dependent variable. Mortality studies were performed using Cox regression. RESULTS: Included were 7718 patients (mean age 71.8 ± 17.4 years, 49.9% males, 27.1% with diabetes). Of these patients, 12.7% had at least one documented hypoglycaemia episode during hospitalization. Patients with decreases in SA levels during hospitalization (group 3) had higher rates of incident hypoglycaemia compared with patients in groups 1 and 2 (21.0% vs. 6.0% and 16.3%, respectively; P < 0.001 for both). Results remained significant after controlling for admission SA. Strong negative correlations were observed between SA and serum osmolarity (r = -0.204, P < 0.0001) and, separately, between changes in SA with changes in serum osmolarity (r = -0.157, P < 0.001), indicating that SA changes were not due to haemodilution. Overall 1-year mortality was 16.7%, and Cox regression analysis showed an increased 1-year mortality in patients in group 3 (27.9%) compared with those in groups 1 and 2 (15.2% and 13.8%, respectively). CONCLUSION: Changes in SA during hospitalization are associated with an increased risk of hypoglycaemia during hospitalization of non-critically ill patients.

Association of albumin and cholesterol levels with incidence of hypoglycaemia in people admitted to general internal medicine units.

AIM: To study the association between serum albumin and cholesterol levels at hospital admission and incident hypoglycaemia among people admitted to internal medicine units. METHODS: In this cross-sectional analysis, we examined the electronic medical records of people hospitalized in internal medicine departments. Data extracted included all glucose measurements as well as serum albumin and cholesterol, which were measured upon admission. A hypoglycaemia event was recorded for a given person if at least one glucose measurement of ≤ 3.9 mmol/l was recorded during the hospital stay. Regression analysis was used to determine which clinical measures predict hypoglycaemia. RESULTS: During the acquisition period, 45 224 people (mean age 68.9 ± 17.8 years, 49.4% male, 21.1% diabetes mellitus) were discharged from internal medicine units. Hypoglycaemia was documented in 7.5% of these individuals (15.4% of people with diabetes vs. 5.5% of those without; P < 0.001). Logistic regression showed that both serum albumin [odds ratio (OR) 0.908, 95% confidence interval (CI) 0.896-0.919; P < 0.001) and cholesterol (OR 0.938, 95% CI 0.896-0.981; P = 0.005] were significantly associated with incident hypoglycaemia. Results remained significant even after controlling for age, sex, average glucose during hospitalization, length of hospital stay, acute infection upon admission, diabetes status, haemoglobin, white blood cell count and C-reactive levels. A combination of hypoalbuminaemia (< 35 g/l) and hypocholesterolaemia (< 3.37 mmol/l) upon admission greatly increased the risk of incident hypoglycaemia (OR 2.544, 95% CI 2.096-3.088; P < 0.001). CONCLUSION: Hypoalbuminaemia and hypocholesterolaemia predict incident hypoglycaemia in the hospital setting among people with and without diabetes mellitus.

Impact of conversion from an open ward design paediatric intensive care unit environment to all isolated rooms environment on incidence of bloodstream infections and antibiotic resistance in Southern Israel (2000 to 2008).

We studied the epidemiology, microbiology, clinical aspects and outcome of bloodstream infections (BSI) in a tertiary paediatric intensive care unit. All BSI episodes were prospectively identified and analysed. The paediatric intensive care unit moved in 2006 from an open-plan unit to a new (all single room) unit. Three hundred and fifty-three BSI episodes occurred in 299 of 4162 patients. Overall, BSI incidence was 85 per 1000 hospitalised children. Fewer BSI episodes occurred during the last two years of the study (2007 to 2008), compared with 2000 to 2006 (70 of 1061 admissions, 6.5% versus 283 of 3101 admissions, 9.1%, respectively, P=0.01). There were 127 of 340 (37.4%) community-acquired and 213 of 340 (62.6%) nosocomial BSI episodes (31 of 1000 and 51 of 1000, respectively). Nosocomial BSI episodes decreased during 2007 to 2008 versus 2000 to 2006 (37.7% versus 55.8%, P=0.03). In 448 instances, pathogens were isolated, 231 (52%) Gram-positive and 188 (42%) Gram-negative. Coagulase-negative Staphylococci, S. pneumoniae and S. aureus (41.1%, 19.9% and 11.7%, respectively) were the most common Gram-positive and Enterobacteriaceae spp. the most frequent Gram-negative organisms (45.2%, of them Klebsiella spp. and E. coli 40% and 29.4%, respectively). A significant decrease was recorded during 2007 to 2008 in Enterobacteriaceae resistance to piperacillin, gentamicin and ciprofloxacin. Thirty of 299 (10%, 9 with S. pneumoniae-BSI) patients died. A significant decrease in BSI and nosocomial incidence and Enterobacteriaceae spp. antibiotic resistance was recorded following the conversion of the paediatric intensive care unit from an open ward to an all isolated rooms environment.

Malnutrition risk in newly hospitalized overweight and obese individuals: Mr NOI.

BACKGROUND/OBJECTIVES: Malnutrition risk and its consequences have not been reported in obese and overweight newly hospitalized patients. To estimate malnutrition risk among newly hospitalized overweight or obese patients, and to assess the effect of body mass index (BMI) on duration of hospitalization and risk of in-hospital death among hospitalized adults at increased risk of malnutrition. SUBJECTS/METHODS: In this survey, all adults newly admitted to internal medicine and surgical departments at a large tertiary medical center, during the 5-week data acquisition period in 2010, were screened for malnutrition risk using the Nutrition Risk Screen (NRS 2002). Malnutrition risk was compared across body weight categories. In addition, overweight/obese subjects were compared by malnutrition risk category. RESULTS: Of the 431 individuals analyzed, 138 were overweight and 105 were obese. Among overweight or obese patients, 23.2% and 24.8%, respectively, were at increased risk for malnutrition. Elevated risk for malnutrition prolonged hospitalization for both overweight and obese patients (from 5.6 ± 7.9 to 10.0 ± 10.3 days (P=0.04) and from 4.8 ± 4.6 to 15.1 ± 25.7 days (P=0.001), respectively). Prolonged hospital stay remained associated with malnutrition risk after controlling for age and BMI. Malnutrition risk significantly increased odds of in-hospital death: odds ratio (OR) 6.4, 95% confidence interval (CI) 1.2-33.2, P=0.03, even after controlling for age and BMI. CONCLUSIONS: Increased malnutrition risk is a frequent finding in newly hospitalized overweight/obese adults, prolongs length of hospital stay and increases risk of in-hospital mortality.

Pneumococcal acute otitis media in infants and children in central Romania, 2009-2011: microbiological characteristics and potential coverage by pneumococcal conjugate vaccines.

OBJECTIVE: To assess the epidemiological and microbiological characteristics of pneumococcal acute otitis media (AOM) in children in Brasov, Central Romania, before the introduction of pneumococcal conjugate vaccine (PCV) into the routine national immunization program. METHODS: All AOM patients aged <5 years who underwent tympanocentesis or presented with purulent otorrhea of ≤24h duration during 2009-2011 were enrolled. RESULTS: Two hundred and twelve consecutive AOM patients had a middle ear fluid (MEF) culture performed; 99 (46.6%) episodes occurred in patients <12 months of age. One hundred and eleven (52.4%) episodes were culture-positive. Tympanocentesis was performed in 142 patients and spontaneous otorrhea cultures in 70 patients. Overall, 114 pathogens were recovered: Streptococcus pneumoniae was the most common isolate (81 isolates, 70.3% of all culture-positive episodes), followed by non-typeable Haemophilus influenzae (26, 20.7%), Streptococcus pyogenes (5, 4.5%), and Moraxella catarrhalis (2, 1.8%). Antibiotic susceptibility and serotyping were performed for 48 (59.3%) S. pneumoniae isolates: 45 (93.8%) were non-susceptible to penicillin (minimal inhibitory concentration (MIC) ≥2.0µg/ml in 24, 53.3%) and 37 (77.1%) isolates had ceftriaxone MIC values ≥0.5µg/ml (16 with MIC >2.0µg/ml). S. pneumoniae non-susceptibility rates to trimethoprim-sulfamethoxazole, erythromycin, and clindamycin were 75.0%, 58.3%, and 35.4%, respectively. All isolates were susceptible to chloramphenicol. Multidrug resistance was found in 33 (68.7%) isolates. The most common S. pneumoniae serotypes were 19F (14, 29.2%), 6B (8, 16.7%), 23F (8, 16.7%), and 14 (6, 12.5%). Serotype 19A was found in three (6.2%) patients and 6A in two (4.1%). Non-PCV13 serotypes represented six (12.6%) of all serotypes (four of them non-susceptible to penicillin). Thirty-six (75.0%) isolates were potentially covered by PCV7, 37 (77.0%) by PCV10, and 42 (87.5%) by PCV13. CONCLUSIONS: (1) S. pneumoniae was the most prevalent pathogen, with frequent antibiotic resistance and multi-resistance patterns; (2) most pneumococcal AOM and multidrug-resistant episodes could be prevented by PCVs.

Prevalence of pilus-encoding islets among acute otitis media Streptococcus pneumoniae isolates from Israel.

We evaluated the distribution of the two known Streptococcus pneumoniae pilus encoding islets (PI-1 and PI-2) among a panel of 113 acute otitis media clinical isolates from Israel. PI-1 was present in 30.1% (n = 34) of the isolates tested, and PI-2 was present in 7% (n = 8). In addition, we found that: (i) the PI positive isolates, 50% of which belong to the international clones Spain(9V)-3 (ST156) and Taiwan(19F)-14 (ST236), correlate with the genotype (as determined by multilocus sequence typing) but not with the serotype; (ii) PI-2 was not present in the absence of Pl-1; and (iii) the frequency of PI-1 was higher among antibiotic-resistant isolates.

Resumenes de articulos de la literatura pediatrica: Otitis media aguda recalcitrante: patogénos, resistencia y estrategia de tratamiento / Abstracts of articles in the pediatric literature: recalcitrant acute otitis media: pathogens, resistance and treatment strategy

El propósito de la siguiente revisión es analizar la experiencia acumulada durante los años 1996 a 2003 en un grupo de niños con otitis media aguda (OMA).

Clinical/otologic score before and during treatment of acute otitis media.

OBJECTIVES: To determine clinical characteristics of AOM at presentation and during therapy according to specific etiologies. PATIENTS AND METHODS: 1003 patients studied during 1996-2001 in antibiotic efficacy studies underwent tympanocentesis and middle ear fluid culture at enrollment and on Day 4-6 (in initially culture-positive patients only). We used a clinical/otologic (CO) score for evaluating severity of fever, irritability and tympanic membrane redness and bulging (0-3 each parameter, maximal score=12). RESULTS: Seven hundred sixty-three patients had positive cultures with 392 (39%) Haemophilus influenzae, 198 (20%) Streptococcus pneumoniae and 173 (17%) mixed H. influenzae and S. pneumoniae infection. Mean CO score was higher in culture-positive versus culture-negative patients (8.21+/-2.17 vs. 7.73+/-2.32, p=0.003) regardless of isolated organism. A marked improvement in CO score was observed on Day 4-6 in all patients: 1.83+/-2.18 in children initially culture-positive and 0.9+/-1.67 in those initially culture-negative (p<0.001). The improvement was greater in patients with eradication versus those with bacteriological failure (CO score 1.52+/-1.82 vs. 2.77+/-2.85, p<0.001). CONCLUSIONS: CO score before treatment, after bacterial eradication or in bacteriologic failures are similar in bacterial AOM and are not predictive of the etiology of the disease.

Long-term thyrotropin-suppressive therapy with levothyroxine impairs small and large artery elasticity and increases left ventricular mass in patients with thyroid carcinoma.

BACKGROUND: Exogenous subclinical hyperthyroidism, caused by long-term thyrotropin (TSH)-suppressive treatment with levothyroxine (LT(4)), is associated with several cardiovascular abnormalities. In order to assess the effect of long-term thyroid hormone-suppressive therapy on the blood vessels and myocardium, we determined the arterial elasticity, using the pulse wave contour analysis. METHODS AND RESULTS: Twenty-six athyreotic patients receiving TSH-suppressive LT(4) therapy for periods ranging from 3 to 21 years at a mean daily dose of 2.25 +/- 0.5 microg/kg per day were included in the study. Twenty six age- and gender-matched healthy subjects served as controls. Arterial elasticity of large and small arteries was evaluated using pulse wave contour analysis method (HDI CR 200, Eagen, MN). Cardiac structure was assessed by two-dimensional echocardiography. We found decreased large artery elasticity in subclinical hyperthyroidism (sHT) patients compared to controls (14.14 +/- 3.38 versus 10.53 +/- 2.43 L/mm Hg x 100, p < 0.000). Small artery elasticity was also lower in patients than in controls (5.42 +/- 1.82 versus 4.30 +/- 1.75 mL/mm Hg x 100, p < 0.056). The echocardiographic data showed significantly increased left ventricular (LV) mass index (101.90 +/- 18.61 versus 88.03 +/- 22.01 g/m(2), p < 0.049) and interventricular septum thickness (10.61 +/- 1.46 versus 9.11 +/- 1.13 mm, p < 0.002) in LT(4)-treated patients compared to controls. CONCLUSIONS: We found impaired vascular elasticity of large and small arteries and increased LV mass in patients receiving long-term TSH-suppressive therapy with LT(4).

Microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in paediatric febrile neutropenic oncology patients: comparison between two consecutive time periods with use of different antibiotic treatment protocols.

This study was devised to look at trends in the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in paediatric febrile oncology patients. The retrospective study compared various microbiological aspects recorded for febrile oncology neutropenic patients treated with two different empirical antibiotic regimens (ceftazidime plus gentamicin during 1998-1999 and piperacillin/tazobactam plus amikacin during 2000-2002). Eighty-one bacteraemic episodes occurred in 41 patients. Overall, 132 (34 during 1998-1999 and 98 during 2000-2002) organisms were isolated: 84 (65%) Gram-negative bacteria, 39 (30%) Gram-positive bacteria and 7 (5%) fungi. Enterobacter spp. incidence decreased from 18 to 6% (P=0.07) while the recovery rates of Gram-positive organisms increased from 24 to 32% (P=0.4) during 2000-2002 compared with 1998-1999. MRSA were not isolated from any episode of bacteraemia. Five (18%) of the 28 Escherichia coli and Klebsiella spp. isolates were beta-lactamase producers (80% [4/5] isolated during 2000-2002). Twenty-seven of 28, 27/27, 23/28, 20/25 and 27/28 of these isolates were susceptible to imipenem, piperacillin/tazobactam, gentamicin, ceftazidime and ciprofloxacin, respectively. Thirty-two of 34 (94%) and 60/74 (81%) of the Gram-negative organisms isolated during 2000-2002 were susceptible to piperacillin/tazobactam and ceftazidime, respectively (P=0.076). No major differences in the microbial spectrum and antibiotic susceptibilities were recorded between the two consecutive study periods. An increase in the number of extended beta-lactamase producing E. coli and Klebsiella spp. occurred during 2000-2002. All beta-lactamase producing organisms were susceptible to piperacillin/tazobactam and initial empirical therapy with piperacillin/tazobactam was more appropriate than ceftazidime to cover most of the pathogens causing bacteraemia.

Acute mastoiditis in infancy: the Soroka experience: 1990-2000.

UNLABELLED: Acute mastoiditis (AM) is an uncommon but serious complication of acute otitis media (AOM). In the pre-antibiotic era, AM was seen more frequently than it is today, but it was rare in infants. However, in the last two decades an increase in the incidence of AM in infancy has been reported in the literature. During the years 1990-2002, we treated 113 patients with 128 episodes of AM; of them, 24 were infants (median age 6 months; 18 males) who suffered from 26 episodes of AM. Twenty developed AM as a complication of their first episode of AOM. One of the four infants with a prior history of AOM suffered from common variable immunodeficiency. A significant increase in the incidence of AM in infants was recorded during the study period (P = 0.01). The most common presenting clinical signs were post-auricular swelling and fever >38 degrees C (77% and 77%, respectively, of all patients). Seventeen episodes of AM were not treated with prior antibiotics. Tympanocentesis was performed in all episodes of AM. Middle ear fluid culture was positive in 17 (65%) of the 26 AM episodes. The most common pathogens cultured were Streptococcus pneumoniae (10 infants, 58% of all pathogens, 3/10 intermediately susceptible to penicillin) followed by Streptococcus pyogenes (4, 23%), non-typable H. influenzae (2, 12%) and S. aureus (1, 6%). Temporal bone CT showed bone destruction in 14 patients; 3 infants had subperiosteal abscesses and 3 lateral sinus thrombosis. Ten infants underwent mastoid surgery due to non-resolution of symptoms and signs with antibiotic therapy. Eight underwent cortical mastoidectomy with two patients undergoing ventilation tube introduction only. The remainder of the infants healed with conservative treatment. CONCLUSIONS: (1) A significant increase in the incidence of AM in infants was recorded over the last decade, though a specific reason for this trend remains uncertain; (2) Most of the cases of AM followed the infant's initial AOM episode, and most of the infants had not received prior antibiotic therapy; (3) The clinical signs and symptoms of AM were more severe in infants than in older patients; (4) While S. pneumonia was the most common pathogen isolated in middle ear fluid cultures, the involvement of S. pyogenes in AM was higher than that reported in AOM.

The Ashkelon Hypertension Detection and Control Program (AHDC Program): a community approach to reducing cardiovascular mortality.

BACKGROUND: Blood pressure (BP) reduction is crucial in reducing cardiovascular (CV) morbidity and mortality in the community. Subjects aged 20-65 seldom visit the primary care clinics, so they are unlikely to be detected without an active outreach screening program. The aim of the project was to prepare a professional doctor-nurse screening team, who will instruct those found to be at high risk in control of their risk factors, in order to reduce CV morbidity and mortality. METHODS: During a 10-year period (1980-1990), teams examined 12,202 subjects, (mean age 51 +/- 7 years, range 20-65 years) accounting for 23.4% of the total regional population. High risk subjects underwent an intensive CV risk factor control program. RESULTS: Subjects (3,506 or 28.6%) were found to have one or more CV risk factors (hypertension, obesity, smoking, hypercholesterolemia). During an average of 2 years, follow-up BP, weight reduction, and smoking cessation remained statistically significant. Total cholesterol was unchanged. Over this period, the standardized mortality ratio (SMR) in the area for acute MI fell from 100 to 76 (P < 0.01), for CV disease from 129 to 107 (P < 0.0001), and for hypertension from 121 to 87 (P < 0.1 NS). The project saved many life-years at no additional net cost to society, and cost effectiveness analysis showed positive results. CONCLUSIONS: A community approach with mainly nonpharmacological treatment is feasible and cost effective in reducing CV morbidity and mortality.

Risk factor profile and achievement of treatment goals among hypertensive patients from the Israeli Blood Pressure Control (IBPC) program--initial cost utility analysis.

AIMS: Blood pressure (BP) reduction is crucial in reducing cardiovascular morbidity and mortality. The IBPC (Israeli Blood Pressure Control) program was initiated in order to enhance the control of modifiable risk factors among high-risk hypertensive patients under follow-up by general practitioners in Israel. The cost effectiveness of an intervention program is an important factor in the decision-making process of its implementation and therefore was evaluated here. The objective of this evaluation is to estimate the costs, monetary savings and benefits in terms of QALYs (quality-adjusted life years) that would be expected if the program were to be expanded to 100 clinics nationwide, enabling around 14800 persons to be treated. METHODS: Hypertensive patients were screened in 30 general practice clinics, supervised by specialists in family medicine, each seeing 1000-5000 patients; 50-250 hypertensive patients were diagnosed at each participating clinic. BP levels, body mass index (BMI), lipid and glucose levels, as well as target organ damage and medications were recorded for all patients. RESULTS: A total of 4948 (2079, 42% males) were registered. Mean age was 64.8 +/- 12 years. After 1 year of follow-up versus baseline, the various parameters were as follows: BP control was achieved in 46.4% vs 29% of all hypertensive patients. LDL control (JNC VI criteria) was achieved in 41.7% vs 31.2% of all patients. Fasting plasma glucose control (glucose < 126 mg/dl) was achieved in 22% vs 19% of diabetic patients and 5.2% vs 3.1% of the diabetics had fasting plasma glucose levels > 200 mg/dl. Obesity (BMI > 30 kg/m2) was noted in 36.7% vs 43.8% at baseline. The cost utility analysis of the reduction in risk factors was calculated based on the international dicta applied to the reduction in risk factors as a result of treatment. For 100 clinics nationwide and 14800 persons to be treated the net saving to health services would be $977993 and the increase in QALYs would be 602 years. CONCLUSIONS: Better risk factor control in hypertensive patients by general practitioners could reduce morbidity and mortality as well as be cost effective.

High-dose liposomal amphotericin B in the therapy of systemic candidiasis in neonates.

High-dose (5-7 mg/kg/day) liposomal amphotericin B was evaluated prospectively during the period 1995-2001 in 41 episodes of systemic candidiasis occurring in 37 neonates (36 of the 37 were premature infants with very low birth weights). Median age at the onset of systemic candidiasis was 17 days. Candida spp. were isolated from blood in all patients and from urine, skin abscesses and peritoneal fluid in 6, 5 and 1 neonates, respectively. Candidiasis was due to Candida parapsilosis in 17 cases, Candida albicans in 15 cases, Candida tropicalis in 5 cases, Candida guilliermondii in 2 cases, Candida glabrata in 2 cases and an unidentified Candida sp. in 1 case. Twenty-eight, five and eight infants received 7, 6-6.5 and 5 mg/kg/day, respectively. Median duration of therapy was 18 days; median cumulative dose was 94 mg/kg. Fungal eradication was achieved in 39 of 41 (95%) episodes; median duration of therapy until fungal eradication was 8.7+/-4.5 days. Fungal eradication was achieved after 10.9+/-4.8 days in patients who had received previous antifungal therapy compared to 8.2+/-4.3 days in those treated with liposomal amphotericin B as first-line therapy. One patient died due to systemic candidiasis on day 12 of therapy. High-dose liposomal amphotericin B was effective and safe in the treatment of neonatal candidiasis. Fungal eradication was more rapid in patients treated early with high doses and in patients who received high-dose liposomal amphotericin B as first-line therapy.

Klebsiella bacteremia in children in southern Israel (1988-1997).

BACKGROUND: Klebsiella spp. have emerged in recent years as a major cause of gram-negative bacteremia in infants and children. We therefore aimed to document the epidemiology, antibiotic susceptibility pattern and outcome of both community-acquired and nosocomial Klebsiella spp. bacteremias in children. PATIENTS AND METHODS: From 1988-1997, 177 episodes of Klebsiella bacteremia, representing 15% of all gram-negative bacteremias, occurred at the Soroka Medical Center in 166 children aged 0-14 years. RESULTS: The overall incidence of Klebsiella bacteremia in southern Israel during the study period was 0.13/1,000, with an increase from 0.1 to 0.2/1,000 children from 1988-1992 to 1993-1997 (p = 0.02). 113 and 64 episodes were recorded in Bedouin Arabs and Jewish children, respectively. The incidence of Klebsiella bacteremia was significantly higher in Bedouins compared to Jewish children (p < 0.001). The incidence of Klebsiella bacteremia increased significantly among Jewish children from 1993-1997 compared to 1988-1992. The incidence of Klebsiella bacteremia was 2/1,000 admissions, with an increase from 1.8 to 2.2/1,000 from 1993-1997 compared to 1988-1992. The incidence of Klebsiella bacteremia was significantly higher among hospitalized Bedouin children compared to Jewish children (3.1 vs 1.4/1,000 admissions, p < 0.001). There were 48 (27%), 24 (14%) and 98 (55%) Klebsiella bacteremia episodes at the pediatric departments, pediatric intensive care unit (PICU) and neonatal intensive care unit (NICU), respectively. 76% of Klebsiella bacteremia episodes were nosocomial; 66% occurred at NICU. 71% and 90% of Klebsiella bacteremia episodes occurring at NICU and PICU, respectively, were nosocomial. The overall incidence of nosocomial infections was 1.5/1,000 admissions, with an increase from 1.2 to 1.8/1,000 from 1993-1997 compared to 1988-1992 (p = 0.03). The resistance rates of Klebsiella spp. to piperacillin, ceftriaxone, ceftazidime and gentamicin were 34%, 17%, 17% and 14%, respectively. A significant increase in the resistance rates to ceftriaxone and ceftazidime was observed from 1993-1997 compared to 1988-92 (21.9% vs 7.8%, p = 0.05 and 21.9% vs 5%, p = 0.03). A significant increase in resistance to ceftriaxone was recorded at PICU and NICU (from 12% and 0%, respectively, from 1988-1992, to 61% and 16%, respectively, from 1993-1997, p = 0.02). Overall mortality rate of Klebsiella bacteremia was 13% (21/167 cases, 12 and eight at PICU and NICU, respectively). CONCLUSION: An increase in Klebsiella bacteremia was recorded in southern Israel during the 10 years of the study. A marked increase in the rate of nosocomial Klebsiella bacteremia occurred at all departments. Resistance to third-generation cephalosporins emerged frequently at PICU and NICU during the last period of the survey.

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

OBJECTIVES: To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). METHODS: In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. RESULTS: Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. CONCLUSIONS: On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.