Beta-lactamase production by Kingella kingae in Israel is clonal and common in carriage organisms but rare among invasive strains.

The purpose of this study was to investigate the prevalence of ß-lactamase and the genomic clonality of a large collection of Kingella kingae isolates from Israeli patients with a variety of invasive infections and asymptomatic pharyngeal carriers. ß-lactamase production was studied by the nitrocefin method and the minimum inhibitory concentrations (MICs) of penicillin and amoxicillin-clavulanate were determined by the epsilon (Etest) method. The genotypic clonality of isolates was investigated by pulsed-field electrophoresis (PFGE). ß-lactamase was found in 2 of 190 (1.1 %) invasive isolates and in 66 of 429 (15.4 %) randomly chosen carriage organisms (p < 0.001). Overall, 73 distinct PFGE clones were identified (33 among invasive organisms and 56 among carriage isolates). ß-lactamase production was found to be limited to four distinct PFGE clones, which were common among carriage strains but rare among invasive strains, and all organisms in the collection belonging to these four clones expressed ß-lactamase. The penicillin MIC of ß-lactamase-producing isolates ranged between 0.094 and 2 mcg/mL (MIC50: 0.25 mcg/mL; MIC90: 1.5 mcg/mL) and that of amoxicillin-clavulanate between 0.064 and 0.47 mcg/mL (MIC50: 0.125 mcg/mL; MIC90: 0.125 mcg/mL). The penicillin MIC of ß-lactamase non-producing isolates ranged between <0.002 and 0.064 mcg/mL (MIC50: 0.023 mcg/mL; MIC90: 0.047 mcg/mL). Although ß-lactamase production is prevalent among K. kingae organisms carried by healthy carriers, the low invasive potential of most colonizing clones results in infrequent detection of the enzyme in isolates from patients with clinical infections. The exceptional presence of ß-lactamase among invasive organisms correlates with the favorable response of K. kingae infections to the administration of ß-lactamase-susceptible antibiotics.

Isolation rates of Brucella melitensis in an endemic area and implications for laboratory safety.

A retrospective study was conducted to assess the potential threat posed by processing blood cultures to clinical microbiology laboratory personnel working in an area endemic for Brucella melitensis in southern Israel. The computerized laboratory records for the 2002-2009 period were reviewed, and the proportion of aerobic vials from which Brucella organisms were isolated out of the total number of positive aerobic blood culture vials was determined. During the 8-year period, B. melitensis was isolated in 514 of 20,620 (2.5%) positive vials. Isolation rate increased at the end of the period reaching a peak of 5.3% in 2008. Between April 2008 and September 2009, the proportion of aerobic blood cultures from which B. melitensis was isolated was even higher than that positive for pneumococci (4.3% and 2.6%, respectively, P < 0.001). Although it has been recommended that processing of Brucella cultures should be confined to a Class II biologic safety cabinet, by the time the organism is identified, extensive manipulation of culture media has already been performed and inadvertent exposure of laboratory personnel may have already occurred. To reduce the risk of transmission, all positive blood culture vials in endemic areas should be processed in a safety cabinet.

Respiratory carriage of the novel Kingella negevensis species by young children.

Kingella negevensis, a novel Kingella species implicated in a pediatric joint infection, has been recently characterized but its epidemiology remains largely unknown. The pharyngeal carriage of K. negevensis was studied by re-examining the results of a previous longitudinal study conducted in a cohort of healthy Israeli children from whom upper respiratory tract specimens were sequentially cultured between the ages of 2 and 36 months. Isolates were identified as K. negevensis by a species-specific nucleic amplification assay and genotyped by pulsed-field gel electrophoresis. ß-lactamase production was determined by the nitrocephin test. Kingella negevensis was detected in 26 of 4,472 (0.58%) oropharyngeal cultures obtained from 24 of 716 children (3.35%) and was not isolated from any of 4,472 nasopharyngeal specimens. Following the first 6 months of life during which none of the children was colonized, the prevalence of carriage gradually increased reaching a peak of 1.09% at 24 months of age and decreased thereafter. Kingella negevensis strains showed genomic heterogeneity, and two clones represented 22 of 26 (84.62%) isolates. Twelve of the 26 (46.15%) isolates, belonging to two distinct clones, produced ß-lactamase. Kingella negevensis shows remarkable similarities with K. kingae in terms of colonization site, age-related patterns of acquisition and carriage, and clonal distribution of ß-lactamase production. Additional research is needed to investigate potential colonization sites of K. negevensis outside the respiratory tract, explore the mechanisms of pharyngeal colonization by the organism, and determine its role as an invasive human pathogen.

Antimicrobial susceptibility testing of Kingella kingae with broth microdilution and disk diffusion using EUCAST recommended media.

OBJECTIVES: Increasing use of improved culture techniques and sensitive nucleic acid amplification assays have resulted in recognition of Kingella kingae as an important cause of invasive infections in young children, especially in septic arthritis, osteomyelitis, bacteraemia, and endocarditis. In 2016, EUCAST established clinical MIC breakpoints for K. kingae (published in EUCAST Clinical Breakpoint Tables v 7.0, 2017). The present study was carried out to produce MIC-zone diameter correlations for K. kingae on an international collection of isolates, with the aim of suggesting zone diameter breakpoints corresponding to the clinical MIC breakpoints. METHODS: Antimicrobial susceptibility testing was performed for 18 clinically relevant agents on a collection of 159 clinical isolates of K. kingae. Broth microdilution MIC determination and disk diffusion were performed according to EUCAST recommendations for fastidious organisms. RESULTS: The correlation between MICs and zone diameters was good for all agents with EUCAST breakpoints for K. kingae. ß-lactamase was detected in 41 isolates (26%) and these isolates were resistant to aminopenicillins. These isolates were also resistant to trimethoprim-sulfamethoxazole. Resistance to tetracyclines was detected in 8% of all isolates. All resistant isolates were correctly categorized for these agents with the proposed zone diameter breakpoints. One isolate, resistant to erythromycin but susceptible to other macrolides, was categorized as susceptible with erythromycin disk diffusion. No resistance was detected for the cephalosporins, carbapenems, and fluoroquinolones tested. CONCLUSION: Based on the results in this study, zone diameter breakpoints for K. kingae calibrated to EUCAST clinical MIC breakpoints were proposed and approved by EUCAST.

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.

Massive clonidine ingestion with hypertension in a 9-month-old infant.

The antihypertensive drug clonidine has a double and antagonistic effect on arterial blood pressure. As a result of activation of peripheral alpha-adrenergic receptors, it causes a transient increase in blood pressure; by a central action it decreases sympathetic tone which results in sustained bradycardia and hypotension. Both central and peripheral effects are experimentally blocked by tolazoline, an alpha-adrenergic blocking agent. The toxic symptoms seen in clonidine poisoning are usually produced by the central effect. A case of severe clonidine poisoning in a 9-month-old infant is reported. The clinical picture included coma, miosis, apneic spells, bradycardia, and hypertension. Rapid and complete recovery was obtained with supportive treatment that included assisted ventilation. No adrenergic blockers or antihypertensive drugs were given. Use of tolazoline in cases of clonidine overdose in children remains controversial. Supportive measures alone may be adequate for even the most severe cases.

Clinical features and epidemiology of invasive Kingella kingae infections in southern Israel.

OBJECTIVE: To characterize the clinical spectrum and epidemiology of invasive Kingella kingae infections in children living in southern Israel. DESIGN: Five-year observational, descriptive study. POPULATION: Children in whom K. kingae was isolated from blood or other normally sterile body fluid. RESULTS: Twenty-five patients with invasive K. kingae infection (13 male and 12 female) were identified. Twenty-four of these children were younger than 2 years. The annual incidence was 14.3, 27.4, and 31.9 cases per 100,000 children < or = 4 years, < or = 24 months, and < or = 12 months, respectively. Seventeen (68%) of 25 patients sought treatment between July and December. Concomitant upper respiratory tract infection or stomatitis was observed in 14 (56%) of the patients, suggesting a respiratory or buccal source for the infection. Four children were bacteremic: 2 of them suffered from a lower respiratory tract infection, and the remaining 2 had bacteremia with no evident focal infection. Twenty-one children had skeletal infections and none of them was bacteremic; 16 had septic arthritis, 3 had osteomyelitis, 1 had both osteomyelitis and septic arthritis of the adjacent joint, and 1 had dactylitis of the hand. Involvement of the ankle was unusually frequent among children with septic arthritis, whereas the calcaneus was involved in 3 of the 4 children with osteomyelitis. Antibiotic treatment resulted in full recovery in all cases, and only 2 patients with septic arthritis required surgical drainage. CONCLUSION: Kingella kingae is a much more common cause of invasive infection in young children than has been previously recognized. The disease has a clear seasonal pattern, usually affects the skeletal system, frequently involves unusual bones and joints, and follows a benign course.

Group A beta-hemolytic streptococcal bacteremia in children.

Twenty cases of Group A beta-hemolytic streptococcal bacteremia in children diagnosed between 1980 and 1987 are reported. Most cases occurred during the winter. The skin and soft tissues were the most common sources of the Group A beta-hemolytic streptococcal bacteremia. Three patients died. Two separate groups of children were observed: (1) a group of 12 young, well-nourished, previously healthy infants, who did not generally develop focal complications and had a favorable course; (2) a group of 8 older children suffering from malnutrition and underlying diseases, such as psychomotor retardation, infected hemangiomata, hemophilia and acute hepatitis B who commonly had focal infections such as pneumonia, meningitis or arthritis/osteomyelitis and had a worse prognosis. M protein-typable strains traditionally related to Group A beta-hemolytic Streptococcus virulence were an inconstant finding in this series.

Early onset pneumococcal sepsis in children hospitalized for noninfectious life-threatening events.

During a 13-year period 9 patients admitted to a pediatric intensive care unit for life-threatening noninfectious conditions developed pneumococcal sepsis within 48 h of admission. All patients were Bedouins, a population group characterized by high prevalence of respiratory carriage of Streptococcus pneumoniae. In populations with high carriage rates of S. pneumoniae, critically ill children appear to be at increased risk of pneumococcal sepsis.

Changing epidemiology of invasive Streptococcus pyogenes infections in southern Israel: differences between two ethnic population groups.

BACKGROUND: Two ethnic populations (westernized Jews and Bedouins in transition from semi-nomadic to sedentary life conditions) living in Southern Israel and receiving inpatient services in the only medical facility of the region. OBJECTIVE: To determine whether the incidence and severity of Streptococcus pyogenes infections among Jewish and Bedouin children have changed over the years. STUDY DESIGN: Retrospective (1980 to 1994), population-based. Medical charts of children younger than 15 years of age hospitalized with S. pyogenes bacteremia and/or severe invasive infection were reviewed. Incidence rates of bacteremia among Jewish and Bedouin children were calculated separately. RESULTS: The incidence of S. pyogenes bacteremia was 2.82/100,000 between 1980 and 1984, was 2.58/100,000 between 1985 and 1989 and rose significantly during 1990 through 1994 to 4.82/100,000 (P < 0.01). The observed increment was the result of a significant increase among the Jews, whereas the incidence among the Bedouin population remained relatively stable. Streptococcal toxic shock syndrome was diagnosed in three Jewish patients between 1992 and 1994. No predominance of any particular streptococcal M-type was observed. CONCLUSIONS: The incidence of pediatric S. pyogenes bacteremia has increased in Southern Israel in recent years. This increase has occurred among the Jewish population, among which the first cases of streptococcal toxic shock syndrome have recently occurred. The increased incidence observed is not the result of dissemination of a single virulent streptococcal clone.

The changing spectrum of group B streptococcal disease in infants: an eleven-year experience in a tertiary care hospital.

Risk factors, clinical syndromes and the case-fatality rates associated with Group B Streptococcus (GBS) infections in infants managed at the University of Rochester Medical Center during 1979 to 1989 were reviewed. Overall 92 episodes of early onset disease (EOD) and 54 of late onset disease (LOD) were diagnosed in 143 infants (3 infants with EOD presented later with LOD). About one-third of patients with EOD and controls were non-white compared with two-thirds of patients with LOD that occurred in racial minority groups. Prematurity and low birth weight were significantly more common in patients with invasive GBS disease than in controls. Eighty-three of 92 (90%) cases of EOD were detected during the first day of life and 10 of 54 (19%) cases of LOD occurred in infants older than 3 months of age. At the time of diagnosis 4% of infants with EOD were asymptomatic, 54% had respiratory disease, 27% had sepsis without a focus, 15% had meningitis and 1% had urinary tract infection or omphalitis. Among infants with LOD 46% had sepsis, 37% meningitis, 7% urinary tract infection, 6% osteomyelitis and/or septic arthritis and 4% cellulitis or pneumonia. Leukopenia and shift to the left were observed in 43 and 61% of episodes of EOD and in 28 and 57% of episodes of LOD, respectively. All infants were promptly treated with antibiotics and vigorous supportive therapy. The case-fatality rate was 13% in EOD and 0 in LOD.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory carriage of Kingella kingae among healthy children.

The role of Kingella kingae as an invasive pathogen of young children is being increasingly recognized, but the niche of the organism in the respiratory tract and its prevalence in the normal flora of children remain unknown. To investigate these two aspects throat and nasopharyngeal cultures were obtained every 2 weeks from two cohorts of children, ages 6 to 42 months on enrollment, attending a day-care center in southern Israel. To determine the age-related prevalence of K. kingae, throat cultures were obtained from children ages 6 months to 14 years hospitalized for elective surgery who had not received antibiotics during the previous 30 days and from healthy infants younger than 6 months attending a well-baby-care clinic for routine vaccinations. During an 11-month follow-up 109 of 624 (27.5%) throat cultures but none of the nasopharyngeal cultures obtained from 48 day-care center attendees grew K. kingae. The monthly prevalence of K. kingae ranged from 6.1 to 34.6% with December and April peaks. Overall 35 of 48 (72.9%) children had at least one positive culture for the organism. Among the 27 children who had > or = 2 positive cultures, continuous and intermittent patterns of carriage were observed. None of the colonized children experienced an invasive K. kingae infection. The prevalence of pharyngeal carriage among surgical patients was 8.0%, and the organism was not isolated from any of the infants younger than 6 months attending the well-baby-care clinic.

Increasing prevalence of penicillin-resistant pneumococcal infections in children in southern Israel: implications for future immunization policies.

Although penicillin-resistant pneumococci (PR-PnC) are recognized as an increasing problem worldwide, data on the prevalence of these strains among pediatric patients are incomplete. The present study was conducted in southern Israel (1) to investigate the frequency of PR-PnC in invasive and middle ear infections in pediatric patients and (2) to assess the impact of resistance on the potential role of the candidate conjugate vaccines in preventing childhood PR-PnC infections. A total of 120 blood or cerebrospinal fluid isolates from 1987 to 1993 and 78 ear isolates from 1992 to 1993 were serogrouped and tested for susceptibility to antibacterial agents. The prevalence of PR-PnC among invasive isolates increased from 16% in the years 1987 to 1991 to 36% in 1992 to 1993 (P = 0.019). This increase was noted mainly for intermediately resistant strains (minimal inhibitory concentration, 0.12 to 1.0 micrograms/ml) whereas the prevalence of highly resistant strains was 3 and 2% for the 2 periods, respectively. The prevalence of PR-PnC among ear isolates in 1992 to 1993 was 42%. Resistance to other antimicrobial agents (one or more of the following: tetracycline, erythromycin, clindamycin and chloramphenicol) was found in 16 (8%) isolates, and multiple resistance (resistance to > or = 3 antibacterial agents) was found in 9 (5%) isolates. Sixty-five (99%) of the 66 resistant isolates belong to Serogroups 6, 14, 19 and 23. The prevalence of these 4 serogroups rose from 37% in 1987 to 1991 to 66% in 1992 to 1993 (P = 0.043). This rise was mainly because of Serogroup 23, the prevalence of which rose from 3% in 1987 to 1991 to 23% in 1992 to 1993 (P < 0.001). Eighty-five percent of all isolates belonging to Serogroup 23 were resistant to penicillin. Because Serogroups 6, 14, 19 and 23 are among the commonest pediatric pneumococcal strains, the newly developed conjugate pneumococcal vaccines contain these 4 serogroups. The selection of antibiotic-resistant strains has thus led to a change in the spectrum of serotypes causing invasive disease and to a situation of potential increase in vaccine coverage for the proposed pneumococcal conjugate vaccines.

Reduction of pneumococcal nasopharyngeal carriage in early infancy after immunization with tetravalent pneumococcal vaccines conjugated to either tetanus toxoid or diphtheria toxoid.

BACKGROUND: Pneumococcal nasopharyngeal colonization is important for transmission of the organisms. We assessed the ability of two tetravalent conjugate vaccines administered in early infancy to prevent carriage of vaccine-related pneumococci. METHODS: A vaccine containing pneumococcal type 6B, 14, 19F and 23F polysaccharide conjugated to tetanus toxoid (Pnc-T) and a vaccine containing the same four polysaccharides conjugated to diphtheria toxoid (Pnc-D) were compared with placebo, in a double blinded study (25 infants per group). Vaccines (or placebo) were injected at 2, 4 and 6 months of age. At 12 months of age a native (nonconjugate) polysaccharide vaccine was administered as a booster. Serum type-specific anticapsular antibody concentrations were measured and nasopharyngeal cultures were obtained at 2, 4, 6, 7, 12 and 13 months of age. RESULTS: In general carriage of all pneumococci (vaccine- and non-vaccine-related) was low at age 2 months and increased with age. However, for the vaccine-related serotypes (6A, 6B, 14, 19F and 23F) carriage was not increased with age in Pnc-D or Pnc-T recipients. Of all cultures obtained after the full primary series, 7 of 72 (10%), 3 of 62 (5%) and 19 or 70 (27%) were positive for the vaccine-related pneumococcal serotypes among the Pnc-D, Pnc-T and placebo recipients, respectively (P = 0.001 for Pnc-D vs. placebo; P = 0.014 for Pnc-T vs. placebo). Most of the antibiotic-resistant isolates belonged to the vaccine-related serotypes. CONCLUSIONS: A significant reduction in the carriage of vaccine-related strains after administration of conjugate vaccines was observed. These preliminary results suggest that transmission of specific pneumococcal serotypes most often associated with disease and antibiotic resistance may at least partially be controlled by immunization.

Predictive value of pneumococcal nasopharyngeal cultures for the assessment of nonresponsive acute otitis media in children.

BACKGROUND: Nonresponsive acute otitis media (NR-AOM) is reported in > 10% of children with AOM treated with antibiotics. Drug-resistant Streptococcus pneumoniae is currently considered the leading cause of antibiotic failures in AOM. Nasopharyngeal colonization with S. pneumoniae was found to increase significantly during episodes of AOM. OBJECTIVES: To investigate the nasopharyngeal colonization with S. pneumoniae during NR-AOM and compare it with that found in AOM not recently treated with antibiotics (NT-AOM); to assess the predictive value of nasopharyngeal pneumococcal cultures results for the bacteriologic assessment of NR-AOM. MATERIALS AND METHODS: Patients age 3 to 48 months with NT-AOM and NR-AOM were prospectively studied. Simultaneous nasopharyngeal cultures for S. pneumoniae and middle ear fluid cultures were obtained at enrollment. Antibiotic susceptibility testing was performed in all S. pneumoniae isolates. Penicillin and ceftriaxone MICs for S. pneumoniae were determined by E-test. The sensitivity, specificity and positive and negative predictive values of positive or negative nasopharyngeal cultures for the presence of S. pneumoniae in middle ear fluid were calculated. RESULTS: We studied 362 and 217 children with NT-AOM and NR-AOM, respectively. Of the children with NT-AOM and NR-AOM, 95 and 97%, respectively, were younger than 2 years of age. S. pneumoniae was isolated in the nasopharynx of 66 and 58% of children with NT-AOM and NR-AOM, respectively. Penicillin-nonsusceptible S. pneumoniae was isolated more frequently from the nasopharynx of patients with NR-AOM than from those with NT-AOM (84% vs. 47%; P < 0.01). Antibiotic susceptibility patterns were similar for S. pneumoniae isolates recovered from the nasopharynx and those from the middle ear fluid in both NT-AOM and NR-AOM. A positive nasopharyngeal culture had only little predictive value for the presence of S. pneumoniae in middle ear fluid (41 and 51% for NT-AOM and NR-AOM, respectively). However, the negative predictive value of nasopharyngeal cultures for recovery of S. pneumoniae in NR-AOM was high and significantly higher in NR-AOM than in NT-AOM (91% vs. 78%, respectively; P = 0.009). The negative predictive value of nasopharyngeal cultures for recovery of antibiotic-resistant S. pneumoniae was 95 and 93% in NT-AOM and NR-AOM, respectively. Conclusions. A significantly higher nasopharyngeal colonization rate with antibiotic-resistant S. pneumoniae was found in patients with NR-AOM than in those with NT-AOM. Negative nasopharyngeal culture for antibiotic-resistant S. pneumoniae practically rules out its presence in middle ear fluid.

A prospective study of neonatal sepsis and meningitis in southern Israel.

OBJECTIVE: To study the epidemiology of neonatal sepsis and meningitis in the Negev area of southern Israel. DESIGN: A prospective 8-year study conducted at the neonatal intensive care unit and pediatric wards of the Soroka University Medical Center. RESULTS: Two hundred twenty-nine cases of hospital and community-acquired neonatal sepsis occurred during the study period. Thirty-two patients (14%) were meningitis. During this period 70,709 births (59% Jews and 41% Bedouins) were recorded; thus the rates of neonatal sepsis and meningitis were 3.2 and 0.5/1000 live births, respectively. One hundred seventeen (4/1000 live births) cases were recorded in Bedouins and 112 (2.6/1000 live births) in Jewish neonates (P < 0.001). Twenty-six percent of all sepsis cases occurred within < 24 h from birth, 25% from Days 2 to 7 of life and 49% between Days 8 and 28. A total of 251 organisms that were considered true pathogens were isolated. Fifty-seven of all isolates were Gram-negative organisms (mainly Klebsiella pneumoniae (20%) and Escherichia coli (16%)). Gram-positive organisms were isolated in 41% of cases. Although E. coli was the most frequently recovered Gram-negative pathogen in community-acquired late onset sepsis, Klebsiella and Enterobacter spp. represented the most commonly isolated Gram-negative organisms in nosocomial late onset sepsis. All Staphylococcus aureus isolates recovered in late onset sepsis were nosocomial. The incidence of Streptococcus agalactiae was 3 times higher in early onset sepsis than in late onset sepsis. All cases of Streptococcus pneumoniae sepsis occurred in Bedouins. CONCLUSIONS: Neonatal sepsis and meningitis rates in southern Israel are similar to those reported in Western Europe and the United States. The incidence of neonatal sepsis is significantly higher for Bedouins than for Jewish neonates. The distribution of the main pathogens is different in southern Israel and although Gram-negative enteric organisms are predominant, S. agalactiae plays a relatively minor role in the etiology of sepsis during the first month of life. In southern Israel the etiology of community-acquired late onset sepsis is different from that of nosocomial late onset sepsis.

Pseudooutbreak of Candida guilliermondii fungemia in a neonatal intensive care unit.

During a 3-week period multiple blood cultures obtained from 14 Neonatal Intensive Care Unit infants and 3 Newborn Unit babies grew Candida guilliermondii, a yeast rarely associated with infections in humans. At the time of detection of positive cultures, most infants had been hospitalized for days or weeks for serious perinatal conditions and treated with antibiotics and intravenous hyperalimentation. Two critically ill premature infants from whom the yeast was isolated were given amphotericin B. In 7 other infants, however, yeasts were recovered on the day of birth, raising the question of pseudofungemia. Exhaustive interrogation on the blood culture practices revealed that when drawing blood for a culture from small infants, "butterfly" needles were often flushed with a diluted heparin solution to prevent blood clotting. Culture of a single lot of diluted heparin vials, prepared at the hospital pharmacy and distributed to the Neonatal Intensive Care Unit and Newborn Unit shortly before the onset of the epidemic, grew between 10,000 and 15,000 colony-forming units of Candida guilliermondii/ml. Removal of contaminated heparin vials and discontinuation of heparinization of needles used for blood cultures resulted in cessation of the epidemic. The present outbreak illustrates the difficulties in recognizing pseudoinfections in sick premature infants and the importance of intensive investigation and intervention during such an outbreak.

Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for treatment of acute otitis media.

BACKGROUND: Trimethoprim-sulfamethoxazole (T/S) has often been used as first and second line of treatment for acute otitis media (AOM). Because of the increasing resistance of Streptococcus pneumoniae and Haemophilus influenzae to T/S, we undertook the present study to investigate the bacteriologic and clinical efficacy of this drug in AOM. METHODS: Fifty-four culture-positive evaluable patients ages 3 to 32 months with AOM were treated with T/S 4/20 mg/kg in two divided daily doses for 10 days. Middle ear fluid (MEF) was cultured at enrollment (Day 1) and on Days 4 and 5 after initiation of treatment. Additional MEF cultures were obtained if clinical relapse occurred. Clinical failure was determined when the symptoms and signs of AOM did not improve or recurred during therapy. Bacteriologic failure was defined by positive culture on Days 4 and 5, or negative on Days 4 and 5 but positive again before the end of treatment. Patients were followed until Day 28 +/- 2. RESULTS: A total of 67 organisms were isolated from MEF specimens of the 54 study patients: S. pneumoniae, 24; H. influenzae, 40; and Streptococcus pyogenes, 3. Fifteen (63%) of 24 S. pneumoniae were nonsusceptible to T/S (trimethoprim MIC, >0.5 microg/ml), of which 10 (67%) were highly resistant to T/S (trimethoprim MIC, > or = 4.0 microg/ml). Twelve (30%) of 40 H. influenzae and all 3 S. pyogenes isolates were nonsusceptible to T/S (MIC > or = 4.0 microg/ml). Bacteriologic eradication occurred in 9 of 9 (100%) and 27 of 27 (100%) T/S-susceptible S. pneumoniae and H. influenzae, respectively, vs. 4 of 15 (27%) and 6 of 12 (50%) T/S-nonsusceptible S. pneumoniae and H. influenzae, respectively (P < 0.001). The 3 patients with S. pyogenes failed bacteriologically. Nine new organisms, not initially isolated, emerged during treatment, 7 of which (77%) were resistant to T/S. Altogether bacteriologic failure (organisms not eradicated plus newly emerged) occurred in 29 (53%) of 54 patients. Clinical failures occurred in 8 (15%) of 54 patients, and in 7 of these 8 cases the clinical failures occurred in those with bacteriologic failures. Ten patients relapsed clinically after completion of treatment and in 8 of them tympanocentesis for MEF culture was performed. Six of these 8 cultures were positive, and the initial pathogen was isolated in 4 of 6 (67%). CONCLUSIONS: A high bacteriologic failure rate as well as a considerable clinical failure rate occurred among patients with AOM treated with T/S. We believe that T/S is no longer an appropriate empiric choice for the treatment of AOM in regions where high T/S resistance among respiratory pathogens is reported.

Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children.

BACKGROUND: Acute invasive diarrhea is a potentially serious condition in children. Because of the increasing resistance of enteric pathogens to commonly used oral antibiotics, intramuscular ceftriaxone has become the routine drug in the treatment of acute invasive diarrhea requiring an emergency visit in southern Israel. The inconvenience of this parenteral regimen created an increased need for oral pediatric formulations for the treatment of invasive diarrhea. OBJECTIVES: To evaluate the efficacy and safety of a suspension formulation of ciprofloxacin in the treatment of acute invasive diarrhea in infants and children. PATIENTS AND METHODS: From July 1996 through December 1997, 201 evaluable children ages 6 months to 10 years (35% <1 year; 70% <3 years) presenting with acute invasive diarrhea at the Pediatric Emergency Room were randomized to receive either ciprofloxacin suspension (10 mg/kg twice a day + im placebo; n = 95) or im ceftriaxone (50 mg/kg/day + placebo suspension; n = 106) for 3 days in a double blind manner. Stool cultures for Shigella, Salmonella, Campylobacter spp. and diarrheagenic Escherichia coli were obtained on Days 1, 3, 4 to 5 and 21 +/- 5. Clinical response and safety were assessed on Days 1, 2, 3, 4 to 5 and 21 +/- 5. RESULTS: We isolated 127 pathogens from 121 (60%) patients: 73 (57%) Shigella; 23 (18%) Salmonella; 18 (14%) E. coli; and 13 (10%) Campylobacter. Overall bacteriologic eradication on Day 4 to 5 was 99% for Shigella, 77% for Salmonella and 77% for Campylobacter, with no difference between the 2 groups. Clinical cure or improvement was observed in 100 and 99% of the ciprofloxacin and ceftriaxone groups, respectively. Serum ciprofloxacin values determined on Day 3 of the treatment were higher in the majority of patients than were the MIC50 and MIC90 values for the Shigella and Salmonella spp. isolated. Possible drug-related adverse events occurred in 13 patients [ciprofloxacin, 8 (8%); ceftriaxone, 5 (4.7%)] and were mild and transient. Joint examination was normal during and after completion of therapy in all patients. CONCLUSION: Oral ciprofloxacin was as safe and effective as intramuscular ceftriaxone for the empiric treatment of acute invasive diarrhea in ambulatory pediatric patients requiring an emergency room visit.

Early eradication of pathogens from middle ear fluid during antibiotic treatment of acute otitis media is associated with improved clinical outcome.

OBJECTIVE: To determine the relation between early bacteriologic eradication and clinical outcome of acute otitis media (AOM) in infants and young children treated with various antibiotics. STUDY DESIGN: The study group consisted of patients ages 3 to 24 months seen at the Pediatric Emergency Room with: (1) symptoms and physical findings consistent with AOM of < or = 7 days duration; (2) no spontaneous perforation or tympanostomy tubes; (3) positive initial middle ear fluid culture; and (4) a follow-up to at least Day 10+/-2 of the study with a second culture performed 72 to 96 h after initiation of antibiotic treatment. Any patient with a positive middle ear fluid culture 72 to 96 h after initiation of antibiotic treatment was considered to have bacteriologic failure. Otologic evaluation was done by an otolaryngologist unaware of the culture results and of the study drug allocation. A clinical score based on body temperature, report of irritability and ear tugging observed by the parents and the appearance and redness of the ear drum as observed by the otolaryngologist was also used for clinical evaluation. RESULTS: The study group consisted of 123 patients, of whom 57 (46%) had positive middle ear fluid 72 to 96 h after initiation of antibiotic treatment. Clinical failure was observed in 21 of 57 (37%) patients in whom bacteriologic eradication did not occur vs. only 2 of 66 (3%) patients with bacteriologic eradication after 3 to 4 days of treatment (P < 0.001). Clinical score for both moderate and severe disease decreased significantly faster in those with bacteriologic eradication than in those in whom middle ear fluid was still culture-positive 72 to 96 h after initiation of treatment. CONCLUSION: Clinical failures in our population were associated with inability to eradicate the causative organisms of AOM from the middle ear fluid within 3 to 4 days after initiation of antibiotic therapy. Most patients (including those without bacteriologic eradication) improved after 3 to 4 days of treatment, but patients with sterile middle ear fluid felt better after 3 to 4 days of treatment than patients in whom middle ear fluid was still culture-positive.