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Candida liver abscesses effectively treated with caspofungin in an extremely low birth-weight infant
Abstracts
hyperlucency, vermian and brain stem hypoplasia. Serum creatine kinase was raised. Electroencephalography was normal. Electromyography revealed myopathic involvement and muscle biopsy was compatible with congenital muscular dystrophy. Conclusions With all these features, a clinical diagnosis of FCMD was made. FCMD may be complicated with febrile and nonfebrile generalized seizures but there is no report of an association between FCMD and any movement disorder such as hyperekplexia in the literature. doi:10.1016/j.earlhumdev.2008.09.160
Abstract UENPS.145 Evaluation of the efficiency of perinatal HIV prevention in Lviv region of Ukraine Korzhynskyy Yuriy⁎,a, Lisnyy Andriya, Sluzhynska Maryanab, Sorokolit Andriyb, Berezhna Ludmylab a Danylo Halytskyy National Medical University, Lviv, Ukraine b Regional Centre for HIV-AIDS Control and Prophylaxis, Lviv, Ukraine Background and aim The rate of spreading of the HIV infection in Ukraine is one of the highest in Europe. Prophylaxis of the mother-to-child transmission of HIV is conducted in Lviv region since 2001. The objective of the present study was to evaluate the efficiency of different prophylactic protocols. Materials and methods During 2001–2007 years 3 different protocols of mother-to-child transmission (MTCT) prophylaxis subsequently were implemented: zidovudine (ZDV) starting at 36 weeks of gestation (introduced in 2001, protocol 1), nevirapine (NVP) to mother and child (introduced in 2003, protocol 2) and ZDV prophylaxis starting at 28 weeks of gestation combined with NVP if started later (introduced in 2005, protocol 3). It was advised for HIV positive (HIV+) mothers not to breastfeed. MTCT rate (MTCTR) and relative risk (RR) associated with each protocol were estimated and RR of protocol infringement was evaluated. 167,977 pregnant women were tested for HIV antibodies. HIV infection was confirmed with immunoblotting and/or PCR. In most children HIV status was determined at 18 months of age. Results Number of HIV+ pregnant women increased from 9 in 2001 to 74 in 2007 in Lviv region (Table 1). The number of HIV+ children infected perinatally increased from 3 in 2002 to 7 in 2007. At the same time MTCTR decreased from 50.00% in 2002 to 9.50% in 2007. 20 HIV+ women and their children did not receive any prophylaxis demonstrating MTCTR of 30%. In 28% of cases the protocols were not followed properly. Only two mothers with their babies were designated to protocol 1 and both infringed it. Nevertheless both children remained HIV negative. RR of following protocol 2 versus no prophylaxis was 0.41(0.15–1.13) and protocol 3 — 0.40 (0.16– 0.96). RR of protocol 2 infringement was 11.3 (1.4–86.5) and of protocol 3 infringement — 22.5 (3.0–167.3). When strictly following the protocol 2 RR of MTCTR was 0.10 (0.013–0.71) and protocol 3 — 0.053 (0.0067–0.41). There was no significant difference in the overall efficiency of protocols 2 (MTCTR = 12.2%) and 3 (MTCTR = 11.0%). At the same time MTCTR in patients strictly following protocols 2 and 3 were as low as 2.94% and 1.59% respectively. Conclusions Amount of HIV+ pregnant women among about 26,000 annual deliveries is increasing in Lviv region while MTCTR is decreasing. Avoidance of the protocol infringement may substantially increase the efficiency of prophylaxis of MTCT.
S63
Table 1 Perinatal HIV infection in Lviv region of Ukraine in 2000–2007 Year
Number of Number of Number of HIV- Number of Mother-to-child deliveries pregnant women positive women HIV-positive transmission checked for HIV who delivered children rate, %
2000 2001 2002 2003 2004 2005 2006 2007
23,366 22,402 23,101 23,975 24,932 25,035 26,423 26,885
18,567 13,570 12,006 22,002 24,218 24,462 26,321 26,831
3 9 6 17 18 23 45 74
0 0 3 6 2 2 3 6
0.0 0.0 50.0 35.3 11.1 8.7 6.7 8.1
doi:10.1016/j.earlhumdev.2008.09.161
Abstract UENPS.146 Candida liver abscesses effectively treated with caspofungin in an extremely low birth-weight infant Filippi Luca, Poggi Chiara⁎, Gozzini Elena, Fiorini Patrizio A. Meyer University Children's Hospital, Florence, Italy Background and aim Candidiasis shows a considerable incidence in neonatal intensive care units, prominently in neonates less than 28 weeks of gestational age. The long-term outcome of survivors appears severe, with higher incidence of cerebral palsy, visual, auditory and neurodevelopmental impairment, and lower assessments of mental and motor development scores. Materials and methods We report a 820 g female infant born at 25 + 5 weeks of gestational age who developed at 13 days of life intestinal obstruction and signs of sepsis. An ultrasound scan detected multiple liver abscesses, with maximal diameters of 21 × 19, 6, 5 and 4 mm. Results With the suspicion of fungal infection, fluconazole therapy was promptly established and at 20 days the infant underwent surgery for ileal atresia. Blood culture was positive for C. albicans, sensitive to fluconazole and amphotericin B. Liposomal amphotericin B was therefore associated to fluconazole. However, on the following days procalcitonin and CRP resulted persistently high, platelets count was persistently low, clinical conditions were deteriorating and blood culture at 34 days remained positive for C. albicans. Therefore therapy with caspofungin, 1 mg/kg daily, was added. In two days procalcitonin and CRP rapidly reduced and ultrasound scan demonstrated at 40 days disappearance of the 3 smallest lesions and reduction of the other one to 16 × 10 mm. Blood culture cleared at 55 days, and the abscess reduced to 6 mm. The abscess was no longer detectable by ultrasound scan at 75 days. The infant was discharged at 120 days of life. Conclusions Caspofungin is an alternative antifungal drug, recommended for adult esophageal and invasive candidiasis and aspergillosis. In recent years caspofungin was successfully experienced in few cases of neonatal candidiasis refractory to conventional drugs. The reported patient is the first ELBW neonate with Candida liver abscesses refractory to fluconazole and liposomal amphotericin B, who was successfully treated with caspofungin. No clinical adverse events attributable to caspofungin were observed during the treatment. Our observation confirms the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal
S64
Abstracts
drugs. More extensive data are needed in order to assess caspofungin efficacy and safety in neonates and to create a specific neonatal schedule. doi:10.1016/j.earlhumdev.2008.09.162
Abstract UENPS.147 Comparison of 4-day and 7-day antibiotic courses for probable neonatal sepsis Saini Shiv Sajan⁎, Dutta Sourabh, Ray Pallab, Narang Anil Postgraduate Institute of Medical Education and Research, Chandigarh, India Background and aim There are no evidence-based guidelines of antibiotic duration for probable neonatal sepsis, although a 7-day course is commonly administered in clinical practice. We hypothesized that a 4-day antibiotic course is not inferior to a 7-day course, amongst neonates, >30 weeks and >1 kg at birth, with probable sepsis, whose clinical signs remit within 96 h and blood culture is sterile.
Materials and methods On line registry was implemented. All newborns admitted to a NICU were enrolled during all admission time. Fields include birth, admission and discharge dates, birth weight and gestational age, days in intensive care, ventilation days, type and days of central venous catheters (CVC), sepsis, pneumonia, meningitis, necrotizing enterocolitis (NEC), isolates, resistance and antibiotics used. The registry started on January 1st, 2008; 23 NICU were enrolled. Results A great variability amongst Units was found concerning days in intensive care, invasive ventilation, CVC use, admitted very low birth weight infants (VLBW) and adherence to the project. On July 20th, 2167 patients had been introduced, accounting for 27,889 admission days, 15% of VLBW, 352 ventilated (ventilation days 3151); 601 infants had had CVC (CVC days 7396). There were 183 episodes of infection in 150 infected newborns; 7% of admitted patients had at least one episode of infection; the rate of episodes of infection was 6.6/1000 admission days, but it climbs to 11/1000 in VLBW infants; there were 166 episodes of sepsis, 19 pneumonia, 1 meningitis and 17 NEC. The rate of associated CVC blood-stream infection was 19/1000 CVC days and that of tracheal tube (TT) associated pneumonia 5/1000TT days. The most common isolate was coagulase negative Staphylococcus. Of the infected newborns 2.7% died because of infection.
Materials and methods Conclusions This was a randomized, controlled, open-labeled trial with blocking and stratification by birth weight. Neonates, >30 weeks and > 1000 g, with signs of sepsis and elevated C reactive protein were enrolled, if not already on antibiotics. Randomization to 4-day or 7-day antibiotic courses was done at 96 h if the baby had remitted, blood culture was sterile and meningitis was ruled out. Subjects were followed up for 15 days after stopping antibiotics, including hospital observation for at least 48 h. The key outcome was “treatment failure” in follow-up, defined as reappearance of signs of sepsis, with or without laboratory evidence and adjudicated to be a relapse by a blinded committee.
The surveillance system provides a valuable knowledge on health-care associated infections enabling neonatologist to improve data and searching causes responsible for basal deviations. doi:10.1016/j.earlhumdev.2008.09.164
Abstract UENPS.149 Candida spp catheter-associated infection in neonatal period
Results Of 240 babies evaluated, 188 were excluded [persistent signs at 96 h: 68; blood culture positive and/or meningitis: 106, no consent: 8 and logistic reasons: 6]. 52 babies were randomized to receive 4-day (n = 26) or 7-day courses (n = 26). Baseline variables were balanced in the 2 groups. Primary outcome assessment could be done in 25 cases in either group. There was no significant difference in the treatment failure rates between the 2 groups (3 in 7-day group vs. 0 in 4-day group, p = 0.23).
Rosmanova Radosveta⁎ Rosmanova R., V. Atanasova, Hr. Hitkova⁎, V. Hristova, Pleven ~ Bulgaria Background and aim
There was no statistically significant difference in the treatment failure rate between the 4-day and 7-day antibiotic course groups among neonates >30 weeks and >1000 g, with probable sepsis without meningitis, who become asymptomatic within 4 days of intravenous antibiotics.
The fungi of Candida species are widely distributed in the environment. They are normal inhabitant of gastro-intestinal and female genital tracts. This determines the higher colonization of the newborns. Candida spp is 4th in frequency among etiologic causes of nosocomial infections. The frequency of fungal catheter-associated infection is about 8% without upward tendency and a main cause is Candida species. The frequency of candidiasis ranges from 1.2 to 5.6% in neonatal intensive cares units. Risk factors are: presence of vaginal Candida as colonization or infection of the mother; characteristics of the newborn immune system; primary broad-spectrum antibiotic therapy, parenteral nutrition and a placement of intravascular catheters.
doi:10.1016/j.earlhumdev.2008.09.163
Materials and methods
Conclusions
Abstract UENPS.148 The Portuguese prospective surveillance system on health-care associated infections in the NICU Maria Teresa Neto, on behalf of the National Programme⁎ Hospital Dona Estefânia, Lisboa, Portugal
We are presented with 7 cases of Candida spp-associated infection. 225 children with placed central venous catheter are treated in NICU of University Hospital — Pleven from 1999 to 2001. The birth weight of neonates ranges from 950 to 4050 g and the gestation age — from 31 to 40 gestation weeks. Reasons of hospitalization are severe asphyxia, birth trauma, prematurity, and seizures. Duration of catheter stay was from 4 to 14 days. Primary combined antibiotic therapy included cephalosporines 2nd generation and aminoglycozides. Results
Background and aim Health-care associated infections (HCAIs) in the Neonatal Intensive Care Unit (NICU) are fearful events with great morbidity and mortality. Prospective surveillance provides knowledge on the endemic rates, microbiology and resistance, helping neonatologists to improve quality on healthcare. The aim is to present the Portuguese surveillance system on HCAIs in NICUs.
Candida in blood culture was found in 1 case only, when there were data of generalized infection. Suspected catheter-associated endogen Candida-sepsis was in 1 newborn, which mother was with vaginal candidiasis and viral hepatitis. Clinical manifestation in other cases was skin-mucous form with colonization of the catheter tip. All children are treated by removal of the catheter and administering of systemic antifungal drugs parenteral and/or peroral — Diflucan or Ketokonazole. The outcome is good in all children.
hyperlucency, vermian and brain stem hypoplasia. Serum creatine kinase was raised. Electroencephalography was normal. Electromyography revealed myopathic involvement and muscle biopsy was compatible with congenital muscular dystrophy. Conclusions With all these features, a clinical diagnosis of FCMD was made. FCMD may be complicated with febrile and nonfebrile generalized seizures but there is no report of an association between FCMD and any movement disorder such as hyperekplexia in the literature. doi:10.1016/j.earlhumdev.2008.09.160
Abstract UENPS.145 Evaluation of the efficiency of perinatal HIV prevention in Lviv region of Ukraine Korzhynskyy Yuriy⁎,a, Lisnyy Andriya, Sluzhynska Maryanab, Sorokolit Andriyb, Berezhna Ludmylab a Danylo Halytskyy National Medical University, Lviv, Ukraine b Regional Centre for HIV-AIDS Control and Prophylaxis, Lviv, Ukraine Background and aim The rate of spreading of the HIV infection in Ukraine is one of the highest in Europe. Prophylaxis of the mother-to-child transmission of HIV is conducted in Lviv region since 2001. The objective of the present study was to evaluate the efficiency of different prophylactic protocols. Materials and methods During 2001–2007 years 3 different protocols of mother-to-child transmission (MTCT) prophylaxis subsequently were implemented: zidovudine (ZDV) starting at 36 weeks of gestation (introduced in 2001, protocol 1), nevirapine (NVP) to mother and child (introduced in 2003, protocol 2) and ZDV prophylaxis starting at 28 weeks of gestation combined with NVP if started later (introduced in 2005, protocol 3). It was advised for HIV positive (HIV+) mothers not to breastfeed. MTCT rate (MTCTR) and relative risk (RR) associated with each protocol were estimated and RR of protocol infringement was evaluated. 167,977 pregnant women were tested for HIV antibodies. HIV infection was confirmed with immunoblotting and/or PCR. In most children HIV status was determined at 18 months of age. Results Number of HIV+ pregnant women increased from 9 in 2001 to 74 in 2007 in Lviv region (Table 1). The number of HIV+ children infected perinatally increased from 3 in 2002 to 7 in 2007. At the same time MTCTR decreased from 50.00% in 2002 to 9.50% in 2007. 20 HIV+ women and their children did not receive any prophylaxis demonstrating MTCTR of 30%. In 28% of cases the protocols were not followed properly. Only two mothers with their babies were designated to protocol 1 and both infringed it. Nevertheless both children remained HIV negative. RR of following protocol 2 versus no prophylaxis was 0.41(0.15–1.13) and protocol 3 — 0.40 (0.16– 0.96). RR of protocol 2 infringement was 11.3 (1.4–86.5) and of protocol 3 infringement — 22.5 (3.0–167.3). When strictly following the protocol 2 RR of MTCTR was 0.10 (0.013–0.71) and protocol 3 — 0.053 (0.0067–0.41). There was no significant difference in the overall efficiency of protocols 2 (MTCTR = 12.2%) and 3 (MTCTR = 11.0%). At the same time MTCTR in patients strictly following protocols 2 and 3 were as low as 2.94% and 1.59% respectively. Conclusions Amount of HIV+ pregnant women among about 26,000 annual deliveries is increasing in Lviv region while MTCTR is decreasing. Avoidance of the protocol infringement may substantially increase the efficiency of prophylaxis of MTCT.
S63
Table 1 Perinatal HIV infection in Lviv region of Ukraine in 2000–2007 Year
Number of Number of Number of HIV- Number of Mother-to-child deliveries pregnant women positive women HIV-positive transmission checked for HIV who delivered children rate, %
2000 2001 2002 2003 2004 2005 2006 2007
23,366 22,402 23,101 23,975 24,932 25,035 26,423 26,885
18,567 13,570 12,006 22,002 24,218 24,462 26,321 26,831
3 9 6 17 18 23 45 74
0 0 3 6 2 2 3 6
0.0 0.0 50.0 35.3 11.1 8.7 6.7 8.1
doi:10.1016/j.earlhumdev.2008.09.161
Abstract UENPS.146 Candida liver abscesses effectively treated with caspofungin in an extremely low birth-weight infant Filippi Luca, Poggi Chiara⁎, Gozzini Elena, Fiorini Patrizio A. Meyer University Children's Hospital, Florence, Italy Background and aim Candidiasis shows a considerable incidence in neonatal intensive care units, prominently in neonates less than 28 weeks of gestational age. The long-term outcome of survivors appears severe, with higher incidence of cerebral palsy, visual, auditory and neurodevelopmental impairment, and lower assessments of mental and motor development scores. Materials and methods We report a 820 g female infant born at 25 + 5 weeks of gestational age who developed at 13 days of life intestinal obstruction and signs of sepsis. An ultrasound scan detected multiple liver abscesses, with maximal diameters of 21 × 19, 6, 5 and 4 mm. Results With the suspicion of fungal infection, fluconazole therapy was promptly established and at 20 days the infant underwent surgery for ileal atresia. Blood culture was positive for C. albicans, sensitive to fluconazole and amphotericin B. Liposomal amphotericin B was therefore associated to fluconazole. However, on the following days procalcitonin and CRP resulted persistently high, platelets count was persistently low, clinical conditions were deteriorating and blood culture at 34 days remained positive for C. albicans. Therefore therapy with caspofungin, 1 mg/kg daily, was added. In two days procalcitonin and CRP rapidly reduced and ultrasound scan demonstrated at 40 days disappearance of the 3 smallest lesions and reduction of the other one to 16 × 10 mm. Blood culture cleared at 55 days, and the abscess reduced to 6 mm. The abscess was no longer detectable by ultrasound scan at 75 days. The infant was discharged at 120 days of life. Conclusions Caspofungin is an alternative antifungal drug, recommended for adult esophageal and invasive candidiasis and aspergillosis. In recent years caspofungin was successfully experienced in few cases of neonatal candidiasis refractory to conventional drugs. The reported patient is the first ELBW neonate with Candida liver abscesses refractory to fluconazole and liposomal amphotericin B, who was successfully treated with caspofungin. No clinical adverse events attributable to caspofungin were observed during the treatment. Our observation confirms the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal
S64
Abstracts
drugs. More extensive data are needed in order to assess caspofungin efficacy and safety in neonates and to create a specific neonatal schedule. doi:10.1016/j.earlhumdev.2008.09.162
Abstract UENPS.147 Comparison of 4-day and 7-day antibiotic courses for probable neonatal sepsis Saini Shiv Sajan⁎, Dutta Sourabh, Ray Pallab, Narang Anil Postgraduate Institute of Medical Education and Research, Chandigarh, India Background and aim There are no evidence-based guidelines of antibiotic duration for probable neonatal sepsis, although a 7-day course is commonly administered in clinical practice. We hypothesized that a 4-day antibiotic course is not inferior to a 7-day course, amongst neonates, >30 weeks and >1 kg at birth, with probable sepsis, whose clinical signs remit within 96 h and blood culture is sterile.
Materials and methods On line registry was implemented. All newborns admitted to a NICU were enrolled during all admission time. Fields include birth, admission and discharge dates, birth weight and gestational age, days in intensive care, ventilation days, type and days of central venous catheters (CVC), sepsis, pneumonia, meningitis, necrotizing enterocolitis (NEC), isolates, resistance and antibiotics used. The registry started on January 1st, 2008; 23 NICU were enrolled. Results A great variability amongst Units was found concerning days in intensive care, invasive ventilation, CVC use, admitted very low birth weight infants (VLBW) and adherence to the project. On July 20th, 2167 patients had been introduced, accounting for 27,889 admission days, 15% of VLBW, 352 ventilated (ventilation days 3151); 601 infants had had CVC (CVC days 7396). There were 183 episodes of infection in 150 infected newborns; 7% of admitted patients had at least one episode of infection; the rate of episodes of infection was 6.6/1000 admission days, but it climbs to 11/1000 in VLBW infants; there were 166 episodes of sepsis, 19 pneumonia, 1 meningitis and 17 NEC. The rate of associated CVC blood-stream infection was 19/1000 CVC days and that of tracheal tube (TT) associated pneumonia 5/1000TT days. The most common isolate was coagulase negative Staphylococcus. Of the infected newborns 2.7% died because of infection.
Materials and methods Conclusions This was a randomized, controlled, open-labeled trial with blocking and stratification by birth weight. Neonates, >30 weeks and > 1000 g, with signs of sepsis and elevated C reactive protein were enrolled, if not already on antibiotics. Randomization to 4-day or 7-day antibiotic courses was done at 96 h if the baby had remitted, blood culture was sterile and meningitis was ruled out. Subjects were followed up for 15 days after stopping antibiotics, including hospital observation for at least 48 h. The key outcome was “treatment failure” in follow-up, defined as reappearance of signs of sepsis, with or without laboratory evidence and adjudicated to be a relapse by a blinded committee.
The surveillance system provides a valuable knowledge on health-care associated infections enabling neonatologist to improve data and searching causes responsible for basal deviations. doi:10.1016/j.earlhumdev.2008.09.164
Abstract UENPS.149 Candida spp catheter-associated infection in neonatal period
Results Of 240 babies evaluated, 188 were excluded [persistent signs at 96 h: 68; blood culture positive and/or meningitis: 106, no consent: 8 and logistic reasons: 6]. 52 babies were randomized to receive 4-day (n = 26) or 7-day courses (n = 26). Baseline variables were balanced in the 2 groups. Primary outcome assessment could be done in 25 cases in either group. There was no significant difference in the treatment failure rates between the 2 groups (3 in 7-day group vs. 0 in 4-day group, p = 0.23).
Rosmanova Radosveta⁎ Rosmanova R., V. Atanasova, Hr. Hitkova⁎, V. Hristova, Pleven ~ Bulgaria Background and aim
There was no statistically significant difference in the treatment failure rate between the 4-day and 7-day antibiotic course groups among neonates >30 weeks and >1000 g, with probable sepsis without meningitis, who become asymptomatic within 4 days of intravenous antibiotics.
The fungi of Candida species are widely distributed in the environment. They are normal inhabitant of gastro-intestinal and female genital tracts. This determines the higher colonization of the newborns. Candida spp is 4th in frequency among etiologic causes of nosocomial infections. The frequency of fungal catheter-associated infection is about 8% without upward tendency and a main cause is Candida species. The frequency of candidiasis ranges from 1.2 to 5.6% in neonatal intensive cares units. Risk factors are: presence of vaginal Candida as colonization or infection of the mother; characteristics of the newborn immune system; primary broad-spectrum antibiotic therapy, parenteral nutrition and a placement of intravascular catheters.
doi:10.1016/j.earlhumdev.2008.09.163
Materials and methods
Conclusions
Abstract UENPS.148 The Portuguese prospective surveillance system on health-care associated infections in the NICU Maria Teresa Neto, on behalf of the National Programme⁎ Hospital Dona Estefânia, Lisboa, Portugal
We are presented with 7 cases of Candida spp-associated infection. 225 children with placed central venous catheter are treated in NICU of University Hospital — Pleven from 1999 to 2001. The birth weight of neonates ranges from 950 to 4050 g and the gestation age — from 31 to 40 gestation weeks. Reasons of hospitalization are severe asphyxia, birth trauma, prematurity, and seizures. Duration of catheter stay was from 4 to 14 days. Primary combined antibiotic therapy included cephalosporines 2nd generation and aminoglycozides. Results
Background and aim Health-care associated infections (HCAIs) in the Neonatal Intensive Care Unit (NICU) are fearful events with great morbidity and mortality. Prospective surveillance provides knowledge on the endemic rates, microbiology and resistance, helping neonatologists to improve quality on healthcare. The aim is to present the Portuguese surveillance system on HCAIs in NICUs.
Candida in blood culture was found in 1 case only, when there were data of generalized infection. Suspected catheter-associated endogen Candida-sepsis was in 1 newborn, which mother was with vaginal candidiasis and viral hepatitis. Clinical manifestation in other cases was skin-mucous form with colonization of the catheter tip. All children are treated by removal of the catheter and administering of systemic antifungal drugs parenteral and/or peroral — Diflucan or Ketokonazole. The outcome is good in all children.