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1.  Staphylococcus Aureus- The Predominant Pathogen in the Neonatal ICU of a Tertiary Care Hospital in Amritsar, India 
Background: An early treatment and the appropriate and the rational use of antibiotics would minimize the risk of severe morbidity and mortality in neonatal sepsis, and reduce the emergence of multi-drug resistant organisms in intensive care units. For the success of an early empiric treatment, a periodic review of the cases to assess any changing trends in the infecting organisms and their antimicrobial susceptibility is important.
AIM: To study the most commonly encountered bacterial pathogens which caused neonatal sepsis and their sensitivity patterns, so that guidelines could be prepared for a rational antibiotic therapy.
Setting and Design: This was a retrospective study which was conducted in the Department of Microbiology and the Neonatal Intensive Care Unit (NICU) at SGRDIMSAR, Amritsar, during June 2011 to June 2012.
Methods and Materials: Blood specimens for culture were drawn from 311 newborns who were admitted in an NICU with sepsis. The specimens were inoculated into brain heart infusion broth. Subcultures were performed on days 1, 2, 3, 5, 7 and 10. The isolates were identified by doing standard biochemical tests. The antibiotic resistance patterns of the isolates were studied by the Kirby Bauer disc diffusion technique.
Results: A total of 131 organisms were isolated from the 311 blood cultures. These included Staphylococcus aureus (n=68), Coagulase Negative Staphylococcus (CoNS) (n=30), Klebsiella pneumoniae (n=10), Acinetobacter baumannii (n=9), Escherichia coli (n=05), Enterobacter cloacae (n=04), Citrobacter diversus (n=02), Pseudomonas aeruginosa (n=02) and Candida (n=01). Staphylococcus aureus was the main pathogen in both early and late-onset sepsis. On antibiotic sensitivity testing, 57.35% of the Staphylococcus aureus isolates were found to be methicillin resistant. More than 90% gram negative rods were resistant to amikacin. The resistance to the third generation cephalosporins varied between 50-55%. The resistance to ciprofloxacin was quite high; however, most of the isolates were susceptible to levofloxacin. A majority of the isolates were susceptible to piperacillin- tazobactum and imipenem.
Conclusion: The present study emphasized the importance of periodic surveys on the microbial flora which was encountered in particular neonatal settings to recognize the trend.
PMCID: PMC3576753  PMID: 23450439
Septicaemia; Drug resistance; Antimicrobial sensitivity tests; S.aureus neonate; India
2.  Isolation of MRSA, ESBL and AmpC – β -lactamases from Neonatal Sepsis at a Tertiary Care Hospital 
Background and Objectives: The emergence of methicillin resistant Staphylococcus aureus (MRSA) and extended spectrum β–lactamases (ESBLs) in neonatal intensive care unit patients is increasing.
This study aims to find out the bacteriological profile in neonatal sepsis and study their antimicrobial susceptibility pattern including detection of MRSA and ESBLs.
Materials and Methods: This study was conducted for a period of one and a half years from January 2010 to June 2011 in a tertiary care hospital in Chennai. A total of 182 blood samples were collected using sterile precautions. They were processed following standard laboratory protocol. Antibiogram was done using appropriate antibiotics by Kirby-Bauer disc diffusion method. Isolated Staphylococcus aureus were tested for methicillin resistance using Cefoxitin disc (30μg), ESBL was detected using combined disc method, MIC reduction and Polymerase chain reaction, metallobetalactamases using EDTA and Amp-C beta lactamases using AmpC disc test. C-reactive protein (CRP) was estimated for all the cases.
Results: Out of the 182 cases, 110 (60.4%) were culture positive. Fifty five (63.9 %) of early onset sepsis cases had Gram negative bacteria (GNB) and 19 (79.1%) of late onset sepsis cases had Gram positive bacteria. Out of the total pathogens, 31 (28.1%) were Klebsiella pneumoniae and 30 (27%) were Staphylococcus aureus.
17 (56.6 %) of Staphylococcus aureus were found to be MRSA and they were 100% sensitive to Vancomycin. 33 (67.3%) of Enterobacteriaceae were ESBL producers. ESBL isolates were 100% sensitive to Imipenem. Three (6.1%) of Enterobacteriaceae were AmpC producers and 3 (27.2%) of Pseudomonas aeruginosa were MBL producers. CRP was positive in 99 (54.3%) cases, out of which 94 (94.9%) were culture positive.
Conclusion: Klebsiella spp. and Staphylococcus aureus were the commonest bacteria causing neonatal sepsis in this centre. Multidrug resistance among the isolates was common. Early diagnosis and institution of specific antibiotics after studying the sensitivity pattern will help in reducing neonatal morbidity and mortality and prevent emergence of drug resistant strains.
PMCID: PMC4129330  PMID: 25120982
C-reactive protein; Extended spectrum beta lactamases; Klebsiella pneumoniae; Methicillin resistant; Neonatal sepsis; Staphylococcus aureus; Staphylococcus aureus
3.  Neonatal sepsis at Muhimbili National Hospital, Dar es Salaam, Tanzania; aetiology, antimicrobial sensitivity pattern and clinical outcome 
BMC Public Health  2012;12:904.
Neonatal sepsis contributes significantly to morbidity and mortality among young infants. The aetiological agents as well as their susceptibility to antimicrobial agents are dynamic. This study determined aetiology, antimicrobial susceptibility and clinical outcome of neonatal sepsis at Muhimbili National Hospital.
Three hundred and thirty neonates admitted at the Muhimbili National Hospital neonatal ward between October, 2009 and January, 2010 were recruited. Standardized questionnaires were used to obtain demographic and clinical information. Blood and pus samples were cultured on MacConkey, blood and chocolate agars and bacteria were identified based on characteristic morphology, gram stain appearance and standard commercially prepared biochemical tests. Antimicrobial sensitivity testing was performed for ampicillin, cloxacillin, gentamicin, amikacin, cefuroxime and ceftriaxone on Mueller Hinton agar using the Kirby Bauer diffusion method.
Culture proven sepsis was noted in 24% (74/330) of the study participants. Isolated bacterial pathogens were predominantly Staphylococcus aureus, Klebsiella spp and Escherichia coli. Klebsiella spp 32.7% (17/52) was the predominant blood culture isolate in neonates aged below seven days while Staphylococcus aureus 54.5% (12/22) was commonest among those aged above seven days. Staphylococcus aureus was the predominant pus swabs isolate for both neonates aged 0–6 days 42.2% (98/232) and 7–28 days 52.3% (34/65). Resistance of blood culture isolates was high to ampicillin 81.1% (60/74) and cloxacillin 78.4% (58/74), moderate to ceftriaxone 14.9% (11/74) and cefuroxime 18.9% (14/74), and low to amikacin 1.3% (1/74). Isolates from swabs had high resistance to ampicillin 89.9% (267/297) and cloxacillin 85.2 (253/297), moderate resistance to ceftriaxone 38.0% (113/297) and cefuroxime 36.0% (107/297), and low resistance to amikacin 4.7% (14/297). Sepsis was higher in neonates with fever and hypothermia (p=0.02), skin pustules (p<0.001), umbilical pus discharge and abdominal wall hyperemia (p=0.04). Presence of skin pustules was an independent predictor of sepsis OR 0.26, 95% CI (0.10-0.66) p=0.004. The overall death rate was 13.9% (46/330), being higher in neonates with sepsis 24.3% (18/74) than those without 10.9% (28/256), p=0.003.
Staphylococcus aureus was predominant isolate followed by Klebsiella and Escherichia coli. There was high resistance to ampicillin and cloxacillin. Mortality rate due to neonatal sepsis was high in our setting. Routine antimicrobial surveillance should guide the choice of antibiotics for empirical treatment of neonatal sepsis.
PMCID: PMC3503784  PMID: 23095365
4.  Neonatal Sepsis: High Antibiotic Resistance of the Bacterial Pathogens in a Neonatal Intensive Care Unit of a Tertiary Care Hospital 
To study the bacterial pathogens causing neonatal sepsis and their sensitivity pattern so that guidelines can be prepared for empirical antibiotic therapy.
Materials and Methods:
We conducted a prospective analysis of all the cases admitted to the neonatal intensive care unit (NICU) of a tertiary care hospital and studied the culture and sensitivity pattern of organisms isolated. The neonates who presented with signs and symptoms of septicemia, with/without pneumonia and/or meningitis were studied and a detailed record of the maturity, age at onset, sex, birth weight (weight on admission for home deliveries), symptoms and signs along with the maternal risk factors was made. The cases with suspect sepsis were screened using various screening markers. Blood culture was done in all the cases, while cerebrospinal fluid was analysed only in those indicated. Sensitivity of the isolated organism was tested by Kirby Bauer disc diffusion techniques and various drug resistance mechanisms were studied.
Out of the 190 neonates (M:F=1.22:1) admitted to the NICU, 60 (31.57%) shows blood culture positive. Ninety-five percent cases were due to early onset septicemia. Thirty one neonates had Gram negative, twenty seven had Gram positive septicemia and two had candidial infection. Seventy percent Gram-positive isolates were resistant to penicillin. Ninety percent Gram negative isolates were resistant to gentamycin and ampicillin. Carbapenem resistance mechanisms such as ESBL.
There is an increasing trend of antibiotic resistance to the commonly used and available drugs. Continuous surveillance for antibiotic susceptibility should be done to look for resistance pattern.
PMCID: PMC3743139  PMID: 24027694
Early onset septicemia; Kirby Bauer disc diffusion; neonatal sepsis; resistance mechanisms; surveillance
5.  Occurrence of drug-resistant bacteria in communal well water around Port Harcourt, Nigeria. 
Epidemiology and Infection  1989;103(1):193-202.
A total of 108 raw water samples was collected from 36 wells at nine shanty settlements around Port Harcourt, Nigeria, over a period of 7 months. Samples were analysed for their bacteriological quality. Selected bacterial strains isolated from the samples were tested for their susceptibility to ten commonly used antibiotics. The organisms isolated include Pseudomonas spp., Klebsiella spp., Staphylococcus spp., Proteus spp., Enterococcus faecalis, Aeromonas spp., Escherichia coli, Chromobacterium spp., Flavobacterium spp., and Serratia spp. Out of 300 strains tested, 23 (6.9%) were susceptible to all the antibiotics, 277 (92.3%) were resistant to at least one antibiotic and 232 (77.3%) were resistant to two or more antibiotics. The epidemiological significance of these results is discussed.
PMCID: PMC2249474  PMID: 2776852
6.  Bacteraemia in Malawian neonates and young infants 2002–2007: a retrospective audit 
BMJ Open  2012;2(3):e000906.
To assess the causes of bacteraemia in young infants and susceptibility to first-line antibiotics (benzylpenicillin plus gentamicin) at the Queen Elizabeth Central Hospital (QECH), Malawi during 2002–2007.
Retrospective analysis of demographic and microbiological data using laboratory records.
QECH is Malawi's largest hospital with 7000 neonates admitted annually, 9% for septicaemia.
All infants aged 60 days or less admitted to QECH that had a blood culture taken over the 6-year period.
Main outcome measures
6754 blood cultures were taken. 3323 organisms were isolated: one-third were pathogens, two-thirds contaminants. Gram-positive organisms (53%) were more common than gram-negatives (47%). Four organisms made up half of all pathogens: Staphylococcus aureus (15.3%), group B streptococci (13.5%), non-typhoidal salmonellae (12.6%) and Escherichia coli (10.5%). Apart from non-typhoidal salmonellae and Streptococcus pneumoniae, most organisms were more common in the first week of life than later. Overall, 28% of isolates during 2002–2007 were resistant to first-line antibiotic, higher than observed during 1996–2001 (22%). Penicillin susceptibility fluctuated while gram-negative resistance to gentamicin increased from 17% to 27% over the study period.
In the QECH, pathogens causing young infant sepsis are an unusual mix of organisms seen in both developed and developing countries. Resistance to first-line antibiotics is higher than observed in most studies. Ongoing monitoring is needed and clinical outcome data would aid interpretation of findings. A high proportion of blood cultures were contaminated with skin flora—improved training and supervision of phlebotomists are needed to improve the utility of taking blood cultures.
Article summary
Article focus
Identification of bacterial causes of sepsis in young infants aged 2 months or less who presented to the QECH, Malawi during 2002–2007.
Documentation of antibiotic resistance patterns of bacterial pathogens isolated during this period.
Changes in aetiology and antibiotic resistance during this 6-year period compared with an earlier audit (1996–2001).
Key messages
We found an unusual range of organisms infecting young infants, a range that lay between those classically observed in developed countries and those commonly reported in developing countries illustrating the complexities of local microbial ecology.
We documented a concerning level of resistance to empirical first-line antibiotics: 28% of isolates were resistant during 2002–2007 compared with 22% during 1996–2001.
The high number of horizontally acquired pathogens and the high proportion of contaminant organisms cultured highlight the need for greater attention to infection control practices.
Strengths and limitations of this study
One of the largest single-site studies of young infant sepsis reviewing every blood culture sample taken for sepsis during a 6-year period (2002–2007).
Comparison with an earlier audit mapping trends in organisms and antibiotic resistance over a 12-year period.
Clinical outcome data were not linked to laboratory registers so the implications of the high level of antibiotic resistance are not immediately clear.
The high number of contaminants isolated may have obscured the growth of fastidious organisms.
PMCID: PMC3358614  PMID: 22587884
7.  Types of Bacteria associated with Neonatal Sepsis in Al-Thawra University Hospital, Sana’a, Yemen, and their Antimicrobial Profile 
This study was undertaken to investigate the organisms causing sepsis in the Neonatal Unit at Al-Thawra Hospital, Sana’a, Yemen, determine their resistance to antibiotics, and recommend policy for empirical treatment.
A total of 158 neonates having one or more signs of sepsis, and aged from 0 to 28 days, were enrolled in this study. A blood sample was taken from each subject, cultured, and then antibacterial susceptibility tests were performed for isolates.
90 (57%) cases yielded positive cultures. Early-onset sepsis showed higher positive culture results (61.7%) than late-onset sepsis (32%). Significant positive culture results were found among the group with birth weight 0.9–2 Kg (78.6%). Gram negative bacteria constituted 97.8% of the total isolates, of which Klebsiella pneumoniae was the predominant pathogen (36.7%), followed by Pseudomonas species (30.0%). The commonest symptoms among the cases were respiratory distress (72.2%), jaundice (62.2%), cyanosis (51.1%), and lethargy (47.8%); the mortality rate was 27.8%. All Gram negative bacterial isolates were sensitive to imipenem and some isolates were sensitive to fourth-generation cephalosporins, but most isolates were highly resistant to the majority of other antibiotics tested.
Gram negative organisms were the most frequent causative agents of bacterial sepsis, which is a significant cause of mortality and morbidity in the newborn, and particularly in those of very low birth weight. It can also be concluded that imipenem and fourth-generation cephalosporins can be used for empirical treatment of bacterial sepsis.
PMCID: PMC3286716  PMID: 22375258
Sepsis; Neonatal; Early-onset; Late-onset; Drug resistance; Treatment, empirical; Sanaa; Yemen
8.  Early-onset sepsis in a neonatal intensive care unit in Beni Suef, Egypt: bacterial isolates and antibiotic resistance pattern 
Korean Journal of Pediatrics  2013;56(8):332-337.
To identify the frequency of bacterial isolates in early-onset neonatal sepsis (EONS) and their antimicrobial resistance pattern.
A retrospective study of EONS was conducted at the Beni Suef University Hospital from September 2008 to September 2012. A case of EONS was defined as an infant who had clinical signs of infection or who was born to a mother with risk factors for infection, and in whom blood culture obtained within 72 hours of life grew a bacterial pathogen.
Of 673 neonates screened, there were 138 positive blood cultures (20.5%) (confirmed EONS). Of the recovered isolates, 86.2% were gram-negative pathogens. Klebsiella pneumoniae (42.8%), Enterobacter cloacae (22.5%), and Escherichia coli (13.8%) were the commonest isolated organisms. The most common gram-positive microorganism was Staphylococcus aureus accounting for only 12 isolates (8.7%). All Klebsiella isolates and 93% of Enterobacter isolates were resistant to ampicillin. Gram-negative pathogens had the maximum overall sensitivity to imipenem, cefepime, and ciprofloxacin; whereas, gram-positive isolates were most susceptible to vancomycin, imipenem, and piperacillin.
K. pneumoniae was the predominant causative bacteria of EONS followed by E. cloacae and E. coli. There was a high resistance to ampicillin. Imipenem had the maximum overall activity against the causative bacteria. Continuous surveillance is needed to monitor the changing epidemiology of pathogens and antibiotic sensitivity.
PMCID: PMC3764257  PMID: 24019843
Drug Resistance; Newborn; Sepsis
9.  Bacteriological Profile of Septicemia and the Risk Factors in Neonates and Infants in Sikkim 
Bacterial infections remain an important cause of pediatric mortality and morbidity. It might be possible to reduce these factors by early diagnosis and proper management.
The aim of the study was to analyze the bacteriological profiles with their antibiogram, and to register the risk factors for septicemia in neonates and infants. Setting and design: This observational cross-sectional study was conducted in a tertiary care teaching hospital at Gangtok, Sikkim, India, and included clinically suspected cases of septicemia in neonates and infants.
Materials and Methods:
Blood culture reports were studied in 363 cases of clinically suspected septicemia in neonates and infants, using the standard technique of Mackie and McCartney. The antibiotic sensitivity was performed by Kirby-Bauer's disc diffusion method. Risk factors for sepsis in the children were registered.
Blood culture was positive in 22% of cases. Gram-negative septicemia was encountered in 61% of the culture-positive cases. Pseudomonas and Enterobacter species were the predominant pathogens amongst gram-negative organisms. Most gram-negative organisms were sensitive to Amikacin, Ciprofloxacin, and Co-trimoxazole. The most common gram-positive organism isolated was Staphylococcus aureus (97%). More than 70% of Staphylococci isolated were resistant to Penicillin, but were sensitive to Clindamycin (70%) and Vancomycin (40%). The most important risk factors of septicemia in our study population were preterm birth (31%), followed by respiratory distress (5%) and low birth weight (4%).
As the cultures showed variable antibiogram with complicated patterns of resistance, culture and sensitivity test should be performed in all cases of septicemia.
PMCID: PMC3068578  PMID: 21572608
Developing countries; Infant; Neonate; Septicemia
10.  “Neonatal Sepsis”: Bacteria & their Susceptibility Pattern towards Antibiotics in Neonatal Intensive Care Unit 
Background: Neonatal sepsis is one of the most common causes of neonatal mortality and morbidity, particularly in the developing countries. Its causative bacteria and their respective sensitivity patterns are different in each hospital and region. The objective of this study was to determine the causative bacteria and pattern of susceptibility to antibiotics in NICU of a tertiary care centre, which in turn may help in implementation of empirical therapy.
Material and Methods: This prospective study was carried out at a medical college during the period from 1st April 2011 to 31st March 2013. A total of 364 cases of suspected sepsis were admitted in our NICU during the mentioned period. Out of which, 137 cases were positive for culture. All the neonates of suspected sepsis were screened by using a panel consisting of CRP, ANC, I/T ratio, micro ESR and culture and sensitivity.
Results: A total of 137 cultures were found to be positive out of 364 cases. The most common organism isolated was Staphylococcus aureus (37.22%) followed by Klebsiella pneumoniae (27.01%) and Escherichia coli (19.70%). Other organisms were much less in number, which included pathogenic Streptococci, Coagulase negative Staphylococci (CoNS), Pseudomonas, Acinetobacter and Enterobacter species. The gram positive organisms except Streptococci displayed a high degree of resistance to most penicillins and ciprofloxacin but were sensitive to vancomycin, amikacin and cefepime. There was a high incidence of resistance noted with ampicillin, gentamicin and ciprofloxacin amongst most gram negative organisms’ where-in cefepime, amikacin and meropenem were effective in most cases.
Conclusion: There is an increasing trend of antibiotic resistance to the commonly used first line drugs. Continuous surveillance for antibiotic susceptibility is needed to ensure proper empirical therapy.
PMCID: PMC3879858  PMID: 24392386
Neonates; Empirical therapy; Early onset sepsis; Late onset sepsis; Antimicrobial sensitivity
11.  Lower Respiratory Tract Infections (LTRIs): An Insight into the Prevalence and the Antibiogram of the Gram Negative, Respiratory, Bacterial Agents 
Background: Community acquired respiratory tract infections are one of the commonest health issues globally, which demand frequent visits to the family practitioners. The emergence of antibiotic resistance in the frequently isolated pathogens has complicated the use of the empiric therapy with traditional agents.
Aim: This study was focused on obtaining a comprehensive insight into the microbial profile, its prevalence and the susceptibility patterns of the gram negative bacilli isolates in lower respiratory tract infections.
Methods and Materials: Respiratory samples which were received from the patients at a Medical College Hospital in North Kerala, India were processed according to the standard protocol over a period of one year, from April 2011 to March 2012. The antimicrobial susceptibility was tested by the Kirby-Bauer disc diffusion method as per the CLSI guidelines. The data was interpreted by using the WHO Net antibiotic susceptibility surveillance soft ware
Results: Out of 1750 respiratory samples, 298(17.03%) were culture positive for gram negative bacilli. The highest isolation rate was observed in the 61-80 years age group with a male preponderance and Klebsiella pneumoniae (41.95%) was found to be the predominant organism. The resistance pattern varied for different organisms. Among the different groups of antibacterial agents which were tested, levofloxacin was found to be an effective oral antibacterial against the pathogens which were isolated. The carbapenems (imipenem and meropenem), the betalactum/betalactamase inhibitors (piperacillin/tazobactum) and the aminoglycosides (amikacin) were effective among the parenteral antibacterials. The selection of the appropriate antibacterial therapy should be based on the organisms which are isolated and on the emerging resistance to the conventional therapies.
Conclusion: Owing to the increased concern which surrounds antibiotic resistance and the changing patterns of the bacterial pathogens, the ongoing surveillance of disease and a regular review of the management guidelines are critical.
PMCID: PMC3592286  PMID: 23543819
Gram negative bacilli; Multidrug resistance
12.  Aetiological agents of ventilator-associated pneumonia and its resistance pattern – a threat for treatment 
The Australasian Medical Journal  2013;6(9):430-434.
Ventilator-associated pneumonia (VAP) is a common type of nosocomial pneumonia encountered in intensive care units. There are several aetiological agents which make treatment challenging. Improper antibiotic treatment of ventilated patients may lead to the emergence of multidrug resistant (MDR) pathogens.
A prospective study was performed over a period of 20 months. Our study had two arms: the first, ‘Incidence and risk factors of VAP in a tertiary care hospital’ was the subject of an earlier publication; we therefore present the second investigative arm in this work. The aetiological agents of patients on mechanical ventilation (MV) were identified by standard bacteriological method. The susceptibility pattern was evaluated by Kirby-Bauer disc diffusion method. Extended spectrum beta lactamase (ESBL) testing was performed by combination disc method, and metallo-beta lactamase (MBL) testing was performed by EDTA disk synergy test (EDS).
Late-onset VAP was associated with Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli, while early-onset VAP was commonly caused by members of Enterobacteriaceae, Candida albicans and Staphylococcus aureus. 72.2 per cent of VAP patients had monomicrobial and 27.8 per cent had polymicrobial infection. Out of the 24 isolates obtained from patients with VAP, seven (29.2 per cent) were MDR pathogens. ESBL and MBL production was detected in 40 per cent and 20 per cent of Klebsiella pneumoniae isolated in our study. Around 50 per cent of isolates associated with late-onset VAP were MDR, while 22.2 per cent isolates obtained from patients with earlyonset VAP were MDR.
VAP is a nosocomial pneumonia that is common among ventilated patients. The aetiological agents vary from common organisms to MDR pathogens that are difficult to treat. A proper knowledge of MDR pathogens and early isolation followed by prevention of prolonged antibiotic therapy can reduce the mortality of late onset VAP.
PMCID: PMC3794413  PMID: 24133535
Ventilator associated pneumonia; aetiology; drug resistance
13.  Mortality Pattern in Children: A Hospital Based Study in Nigeria 
Background: Hospital based data on mortality pattern is a reflection of what is obtainable in a community at large. Therefore, data obtained from such review is usually beneficial in re-evaluating existing services and in improving facilities and patient care. The aim of this study was to evaluate the mortality pattern of children admitted into the children medical wards of the University of Port-Harcourt Teaching Hospital from Jan 2007 to December 2008. Materials and Methods: This was a retrospective study. The case files of all patients aged one month to 16 years, admitted into the paediatric wards of University of Port-Harcourt Teaching Hospital, Port-Harcourt, Nigeria over a 2 year period were reviewed. Neonatal and surgical cases were excluded. Results: There were 2,174 admissions during the study period. Sixty one of the total number of admissions died in the children medical wards giving a mortality rate of 2.8%. The youngest child was 2 months and the oldest 10 years. Fifty two (80.3%) were under 5 years. There was male preponderance. Most of the deaths occurred between April and September. The commonest causes of death were HIV/AIDS and bronchopneumonia in the under five age group; while in those above 5 years of age malignancies and HIV/AIDS were the predominant causes. Conclusion: Effective HIV/AIDS control measures will significantly reduce child mortality in our community. Also there is need to have a closer look at the potential risk for malignancies. Health intervention programmes such as integrated management of childhood illnesses and primary health care, which have been shown to reduce childhood deaths significantly, need to be intensified in order to achieve the MDG 4 by 2015.
PMCID: PMC3614794  PMID: 23675160
mortality pattern; children; admission; HIV/AIDS; MDGs
14.  Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza- Tanzania 
BMC Pediatrics  2010;10:39.
Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC), Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis.
This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method.
Among 770 neonates admitted during the study period; 300 (38.9%) neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40%) and 179(60%) had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1%) and 92 (51.4%) among neonates with early and late onset neonatal sepsis respectively (p = 0.466). Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA). Deaths occurred in 57 (19%) of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001), gram negative sepsis (p = 0.0001) and infection with ESBL (p = 0.008) or MRSA (p = 0.008) isolates.
Our findings suggest that lethargy, convulsion, inability to feed, cyanosis, PROM and meconium stained liquor are significantly associated with positive blood culture in both early and late onset disease. Mortality and morbidity on neonatal sepsis is high at our setting and is significantly contributed by positive blood culture with multi-resistant gram negative bacteria.
PMCID: PMC2889942  PMID: 20525358
15.  Bacterial Uropathogens in Urinary Tract Infection and Antibiotic Susceptibility Pattern in Jimma University Specialized Hospital, Southwest Ethiopia 
Urinary tract infection (UTI) is one of the most common bacterial infections encountered by clinicians in developing countries. Area-specific monitoring studies aimed to gain knowledge about the type of pathogens responsible for urinary tract infections and their resistance patterns may help the clinician to choose the correct empirical treatment. Therefore, the aim of this study was to determine the type and antibiotic resistance pattern of the urinary pathogens isolated from patients attending Jimma University Specialized Hospital from April to June 2010.
A hospital based cross sectional stud was conducted and urine samples were collected using the mid-stream “clean catch” method from 228 clinically-suspected cases of urinary tract infections and tested bacteriologically using standard procedures. Antimicrobial susceptibility test was performed for the isolated pathogens using Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute guidelines.
Significant bacteria were detected from 9.2% of the total patients. The most common pathogens isolated were Escherichia coli (33.3%), Klebsiella pneumoniae (19%) and S. saprophyticus (14.3%). E. coli and Klebsiella pneumoniae showed the highest percentage of resistance to ampicillin and amoxacillin (100%) however, all isolates of E. coli and K. pneumoniae were susceptible to ciprofloxacin. S. saprophyticus and S. aureus were resistant to ampicillin (100%) and amoxicillin (66.7%). For all UTI isolates, least resistance was observed against drugs such as ceftriaxone, gentamycin and chloramphenicol.
This study finding showed that E. coli isolates were the predominant pathogens and the presence of bacterial isolates with very high resistance to the commonly prescribed drugs that in turn leaves the clinicians with very few alternative options of drugs for the treatment of UTIs. As drug resistance among bacterial pathogens is an evolving process, routine surveillance and monitoring studies should be conducted to provide physicians knowledge on the updated and most effective empirical treatment of UTIs.
PMCID: PMC3275859  PMID: 22434993
Urinary tract infection; antimicrobial resistance; Jimma; Ethiopia
16.  Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis 
Bacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia.
This was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed.
The most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n = 7, 71%–100%), other Klebsiella species (n = 7, 28%–80%), and Staphylococcus (n = 36, 25%–40%).
The common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high sensitivity to cephalosporins used in the empirical treatment of meningitis. The resistance of the common isolates to penicillin is high. Most ESBL K. pneumoniae were isolated from CSF samples drawn from neonates and were found to be resistant to the antibiotics recommended in the Namibia STGs. Based on the above findings, it is recommended to use a combination of aminoglycoside and third-generation cephalosporin to treat non–ESBL Klebsiella isolates. Carbapenems (e.g., meropenem) and piperacillin/tazobactam should be considered for treating severely ill patients with suspected ESBL Klebsiella infection. Namibia should have a national antimicrobial resistance surveillance system for early detection of antibiotics that may no longer be effective in treating meningitis and other life-threatening infections due to resistance.
PMCID: PMC3987067  PMID: 24764539
Celebrospinal fluid; Antimicrobial resistance; Culture and sensitivity; Empiric therapy; Meningitis; Namibia
17.  Susceptibility of bacterial etiological agents to commonly-used antimicrobial agents in children with sepsis at the Tamale Teaching Hospital 
Bloodstream infections in neonates and infants are life-threatening emergencies. Identification of the common bacteria causing such infections and their susceptibility patterns will provide necessary information for timely intervention. This study is aimed at determining the susceptibilities of bacterial etiological agents to commonly-used antimicrobial agents for empirical treatment of suspected bacterial septicaemia in children.
This is a hospital based retrospective analysis of blood cultures from infants to children up to 14 years of age with preliminary diagnosis of sepsis and admitted to the Neonatal Intensive Care Unit (NICU) and Paediatric Wards of the Teaching Hospital Tamale from July 2011 to January 2012.
Out of 331 blood specimens cultured, the prevalence of confirmed bacterial sepsis was 25.9% (86/331). Point prevalence for confirmed cases from NICU was 44.4% (28/63) and 21.6% (58/268) from the Paediatric ward. Gram positive cocci (GPC) were the predominant isolates with Coagulase positive (32.2%) and Coagulase-negative (28.7%) Staphylococci accounting for 60.9% of the total isolates. Gram negative rods (GNR) comprised 39.1% of all isolates with Klebsiella, E.coli and Salmonella being the most common organisms isolated. Klebsiella was the most frequent GNR from the NICU and Salmonella typhi was predominantly isolated from the paediatric ward. Acinetobacter showed 100.0% susceptibility to Ceftriaxone and Cefotaxime but was resistant (100.0%) to Ampicillin, Tetracycline and Cotrimoxazole. Escherichia coli and Klebsiella were 80.0% and 91.0% susceptible to Ceftriaxone and Cefotaxime respectively. Klebsiella species showed 8.3% susceptibility to Tetracycline but was resistant to Ampicillin and Cotrimoxazole. Escherichia coli showed 40.0% susceptibility to Ampicillin, Chloramphenicol and Cotrimoxazole; 20.0% susceptibility to Tetracycline and 80.0% susceptible to Gentamicin and Cefuroxime. Coagulase negative Staphylococci was susceptible to Gentamicin (72.0%) but Coagulase positive Staphylococci showed intermediate sensitivity to Gentamicin (42.9%).
Coagulase Negative, Coagulase Positive Staphylococci, Salmonella and Klebsiella were the aetiological agents of bloodstream infection among children at TTH. While gram-positive and gram-negative bacteria showed low susceptibility to Ampicillin, Tetracycline and Cotrimoxazole, the GNR were susceptible to Gentamicin and third-generation cephalosporins.
PMCID: PMC3598494  PMID: 23419199
18.  Treatment of Infections in Young Infants in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Frontline Health Worker Diagnosis and Antibiotic Access 
PLoS Medicine  2014;11(10):e1001741.
Anne C. C. Lee and colleagues assess the factors affecting access to treatment for neonatal and infant infections in low- and middle-income countries by conducting a systematic review and meta-analysis of frontline health worker diagnosis and access to antibiotics.
Please see later in the article for the Editors' Summary
Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription?
Methods and Findings
We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%–91%) and lower specificity (62%, 95% CI 48%–75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%–88%) and specificity of 69% (95% CI 54%–83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%–34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data.
Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs.
Review Registration
PROSPERO International prospective register of systematic reviews (CRD42013004586).
Please see later in the article for the Editors' Summary
Editors' Summary
Neonatal mortality—death that occurs during the first 28 days of life—accounts for nearly half of all the deaths that occur in children before they reach their fifth birthday. Worldwide, nearly 3 million neonatal deaths occur every year. Three bacterial infections—sepsis (infection of the bloodstream), pneumonia (infection of the lungs), and meningitis (infection of the brain's protective covering)—are responsible for nearly a quarter of all neonatal deaths. Babies born in low- and middle-income countries (LMICs) are at particularly high risk of developing neonatal bacterial infections because the risk factors for these infections, which include maternal infections and unhygienic delivery care, are more common in LMICs than in high-income countries. Babies born in LMICs are also at a high risk of dying from bacterial infections because access to appropriate medical care and antibiotics is often poor.
Why Was This Study Done?
To reduce neonatal deaths from bacterial infections in LMICs, health care experts need to identify the factors that limit access to medical care and antibiotics in these countries. Are babies dying because health care providers fail to diagnose neonatal bacterial infections, because antibiotics are not available in first-line health facilities, or for some other reason? In this systematic review and meta-analysis, the researchers investigate access to treatment for neonatal bacterial infections in LMICs by first asking whether frontline health workers in LMICs can accurately diagnose bacterial infections in neonates and young infants (babies less than 2 months old). Next, they ask whether antibiotics for treating neonatal infections are available and affordable in LMICs. Finally, they ask how often antibiotics are procured for young children (children up to the age of 5 years) without a prescription. A systematic review uses pre-defined criteria to identify all the research on a given topic; meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 37 published studies, 46 surveys of drug availability and affordability in LMICs (Health Access International databases), and eight surveys of the capacity of health facilities in LMICs to provide quality health care services (service provision assessments) that met their inclusion criteria. Meta-analysis of six studies indicated that a combination of simple clinical signs for the diagnosis of bacterial infection in children predicted very severe disease in young infants with a sensitivity of 87% and a specificity of 62% (“sensitivity” indicates the percentage of true positives detected by a test; “specificity” indicates the percentage of healthy people that a test correctly identifies as healthy) compared to a physician's diagnosis with laboratory testing. Meta-analysis of eight studies indicated that frontline health workers (for example, community health workers) diagnosed very severe disease (including possible bacterial infection) in young infants with a sensitivity of 82% and a specificity of 69% compared to trained physicians. The national surveys analyzed indicated that first-level (primary) health facilities in Africa and South Asia had low, variable stocks of recommended first-line injectable antibiotics and that the cost of these drugs was high. By contrast, some oral antibiotics were widely available at low cost in most regions. Finally, meta-analysis of 11 studies indicated that, in LMICs, 25% of antibiotic purchases for the treatment of young children were obtained without a prescription.
What Do These Findings Mean?
These findings suggest that trained frontline health workers should be able to identify most young infants who have possible bacterial infections in LMICs but may also diagnose bacterial infections in many young infants who are not infected. This may lead to the inappropriate use of antibiotics and facilitate the emergence of antibiotic resistance. These findings also show that the availability and affordability of first-line injectable antibiotics is low in many health facilities in Africa and Asia. The lack of neonatal-specific data on illness recognition, antibiotic formulations and availability, and other aspects of this systematic review and meta-analysis are likely to limit the accuracy of these findings. Nevertheless, the researchers suggest that, to decrease the neonatal death toll in LMICs, governments, policymakers, and the pharmaceutical industry need to work together to improve the diagnosis of neonatal bacterial infections and to increase the availability, affordability, and appropriate use of antibiotics for the treatment of these infections.
Additional Information
Please access these websites via the online version of this summary at
WHO provides information on global efforts to reduce global child mortality and on ending preventable neonatal deaths (available in several languages)
The United Nations Children's Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on global efforts to reduce child mortality , and its Childinfo website provides detailed statistics about neonatal survival and health; its “Committing to Child Survival: A Promise Renewed” webpage includes links to its 2013 progress report and to videos about ending preventable child deaths
The WHO has published a report entitled UN Commission on Life Saving Commodities for Women and Children
The Healthy Newborn Network (NHH) is an online community of more than 80 partner organizations that addresses critical knowledge gaps in newborn health; its website includes information on neonatal infections in LMICs
Kidshealth, a resource provided by the not-for-profit Nemours Foundation, has information for parents on neonatal infections (in English and Spanish)
The MedlinePlus Encyclopedia has a page on neonatal sepsis (in English and Spanish)
A personal story about fatal neonatal bacterial meningitis is available on the website of Meningitis UK, a not-for-profit organization; the site also includes a survivor story
PMCID: PMC4196753  PMID: 25314011
19.  A Five-Year Experience of Carbapenem Resistance in Enterobacteriaceae Causing Neonatal Septicaemia: Predominance of NDM-1 
PLoS ONE  2014;9(11):e112101.
Treatment of neonatal sepsis has become a challenge with the emergence of carbapenemase-producing bacteria. This study documents the trend of carbapenem susceptibility in Enterobacteriaceae that caused septicaemia in neonates over a five year period (2007–2011) and the molecular characterisation of Enterobacteriaceae resistant to carbapenems and cephalosporins. Hundred and five Enterobacteriaceae including Escherichia coli (n = 27), Klebsiella pneumoniae (n = 68) and Enterobacter spp. (n = 10) were isolated from blood of septicaemic neonates followed by antibiotic susceptibility tests, determination of MIC values, phenotypic and genotypic detection of β-lactamases. Carbapenem was the most active antimicrobial tested after tigecycline. CTX-M type was the most prevalent ESBL throughout the period (82%). New Delhi Metallo-β-lactamase-1 (NDM-1), which is a recent addition to the carbapenemase list, was the only carbapenemase identified in our setting. Fourteen percent of the isolates possessed blaNDM-1. Carbapenem non-susceptibility was first observed in 2007 and it was due to loss of Omp F/Ompk36 in combination with the presence of ESBLs/AmpCs. NDM-1 first emerged in E. coli during 2008; later in 2010, the resistance was detected in K. pneumoniae and E. cloacae isolates. NDM-1-producing isolates were resistant to other broad-spectrum antibiotics and possessed ESBLs, AmpCs, 16S-rRNA methylases, AAC(6′)-Ib-cr, bleomycin resistant gene and class 1 integron. Pulsed field gel electrophoresis of the NDM-1-producing isolates indicated that the isolates were clonally diverse. The study also showed that there was a significantly higher incidence of sepsis caused by NDM-1-harbouring isolates in the male sex, in neonates with low birth weight and neonates born at an extramural centre. However, sepsis with NDM-1-harbouring isolates did not result in a higher mortality rate. The study is the first to review the carbapenem resistance patterns in neonatal sepsis over an extended period of time. The study highlights the persistence of ESBLs (CTX-Ms) and the emergence of NDM-1 in Enterobacteriaceae in the unit.
PMCID: PMC4236051  PMID: 25406074
20.  Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(8):e1001502.
Grace Chan and coauthors conducted a systematic review and meta-analysis of studies evaluating the risk of neonatal infection or colonization during the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.
Please see later in the article for the Editors' Summary
Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.
Methods and Findings
We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors.
Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis.
Please see later in the article for the Editors' Summary
Editors' Summary
Millennium Development Goal 4 (MDG4)—one of eight goals agreed by world leaders in 2000 to eradicate extreme poverty globally—aims to reduce under-five mortality (deaths) to one-third of its 1990 level (12 million deaths). Progress towards reducing child mortality has accelerated recently, but MDG4 is unlikely to be met, partly because of slow progress towards reducing neonatal mortality—deaths during the first 28 days of life. Neonatal deaths now account for a greater proportion of global child deaths than in 1990. Nearly half of the children who die before their fifth birthday die during the neonatal period, with babies born in low-middle-income countries in sub-Saharan Africa and southern Asia being at the highest risk of neonatal death. Bacterial infections such as infections of the bloodstream (bacteremia/sepsis), lungs (pneumonia), and the brain's protective covering (meningitis) are responsible for a quarter of neonatal deaths. Newborns can acquire infections during birth by picking up bacteria (in particular Group B streptococcus or GBS) that are present in their mother's reproductive tract and that may or may not cause disease in the mother. Bacteria colonizing the maternal perineum (the area between the anus and the vagina) can move up the vaginal canal into the amniotic sac (the fluid-filled bag in which the baby develops). Maternal bacteremia is another source of bacterial transmission from mother to fetus. Other risk factors for neonatal infection include pre-labor rupture of the membranes (PROM) of the amniotic sac, preterm PROM, and prolonged rupture of membranes.
Why Was This Study Done?
In high-income settings, prophylactic (preventative) antibiotic treatment during labor (based on microbiological screening or risk factors such as PROM) and early diagnosis and treatment of sepsis in newborn babies has greatly reduced deaths from early-onset neonatal bacterial infection. Yet, relatively little is known about the risk factors and transmission pathways for this condition globally. In this global systematic review and meta-analysis, the researchers estimate the risk of neonatal bacterial infections (excluding sexually transmitted diseases) among newborns of mothers with bacterial infection or colonization around the time of birth. A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis is a statistical method for combining the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 83 studies (only seven of which were undertaken in settings with high neonatal mortality) that included data on laboratory-confirmed maternal infection, maternal infection indicated by clinical signs and symptoms, maternal colonization (positive bacterial cultures from the reproductive tract without any signs or symptoms of infection), or risk factors for infection such as PROM and data on neonatal infection (laboratory-confirmed or clinically indicated) or colonization. Because different studies used different definitions for infection and colonization, the researchers pooled the data from subsets of the studies using random effects meta-analysis, which allows for heterogeneity (inconsistencies) between studies. Newborns of mothers with laboratory-confirmed infection had a 6.6-fold higher risk of laboratory-confirmed infection than newborns born to mothers without laboratory-confirmed infection. Newborns of mothers with bacterial colonization had a 9.4-fold higher risk of laboratory-confirmed infection than newborns of non-colonized mothers. Finally, compared to newborns of mothers without risk factors for infection, newborns of mothers with PROM or other risk factors had a 2.3-fold higher risk of infection.
What Do These Findings Mean?
These findings indicate that an increased risk of early-onset neonatal infection is associated with maternal infection and maternal colonization and provide some quantification of the excess risk. Because all the studies were facility-based and mostly from urban settings in high-income countries, these findings provide no information about the risk of neonatal infection among home births, rural births or births at community facilities in low-income countries, which limits their generalizability. Other aspects of the studies included in this systematic review and meta-analysis are also likely to limit the accuracy of the findings. Nevertheless, these findings suggest that better diagnosis and treatment of maternal infections and colonization in low- to middle-income countries where neonatal mortality is high might substantially reduce the incidence of neonatal infections and that the development of a simple algorithm that combines clinical signs and risk factors to diagnose maternal infections might be useful in regions where laboratory facilities are unavailable. Moreover, they highlight the need for more studies of maternal and neonatal infection and colonization in resource-poor settings with high neonatal mortality.
Additional Information
Please access these Web sites via the online version of this summary at
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4 and its Childinfo website provides detailed statistics about neonatal survival and health; its Committing to Child Survival: a Promise Renewed webpage includes links to its 2012 progress report and to a video about how new health centers are helping India battle high neonatal death rates
The World Health Organization has information about Millennium Development Goal 4 and about newborn health (some information in several languages)
Countdown to 2015 provides additional information on maternal, newborn, and child survival, including its 2012 report Building a Future for Women and Children
Kidshealth, a resource provided by the not-for-profit Nemours Foundation, has information on neonatal infections for parents (in English and Spanish)
The MedlinePlus Encyclopedia has a page on neonatal sepsis (in English and Spanish)
A personal story about fatal neonatal bacterial meningitis is available on the website of Meningitis UK, a not-for profit organization; the site also includes a survivor story
PMCID: PMC3747995  PMID: 23976885
21.  Etiology of Neonatal Blood Stream Infections in Tbilisi, Republic of Georgia 
Neonatal blood stream infections (BSI) are major cause of morbidity and mortality in developing countries. It is crucial to continuously monitor the local epidemiology of neonatal BSI to detect any changes in patterns of infection and susceptibility to various antibiotics.
To examine the etiology of BSI in two neonatal intensive care units (NICU) in the Republic of Georgia, a resource-poor country, and to determine antibiotic susceptibility of the isolated organisms.
Cross-sectional study among all septic infants was conducted in NICU of two pediatric hospitals in Tbilisi between 09/2003-09/2004.
A total of 200 infants with clinical signs of sepsis were admitted in two NICUs. Of these, 126 (63%) had confirmed bacteremia. Mortality rate was 34%. A total of 98 (78%) of 126 recovered isolates were Gram-negative organisms, and 28 (22%) were Gram-positive. Klebsiella pneumoniae was the most common pathogen, accounting for 36 (29%) of 126 isolates, followed by Enterobacter cloacae – 19 (15%), and S. aureus – 15 (12%). The gram-negative organisms showed high degree of resistance to commonly used antibiotics such as ampicillin, amoxicillin/clavulanate, and comparatively low resistance to amikacin, ciprofloxacin, carbapenems, and gentamicin; 40% of S. aureus isolates were methicillin resistant (MRSA). In multivariate analysis only umbilical discharge was a significant risk factor for having positive blood culture at admission to NICU (PR=2.25, 95% CI 1.82-2.77).
Neonatal BSI was mainly caused by gram-negative organisms, which are developing resistance to commonly used antibiotics. Understanding the local epidemiology of neonatal BSI can lead to the development of better medical practices, especially more appropriate choices for empiric antibiotic therapy, and may contribute to improvement of infection control practices.
PMCID: PMC2695829  PMID: 19058989
blood stream infections; Republic of Georgia; neonatal
22.  Bacterial isolates of early-onset neonatal sepsis and their antibiotic susceptibility pattern between 1998 and 2004: an audit from a center in India 
Epidemiology and surveillance of neonatal sepsis helps in implementation of rational empirical antibiotic strategy.
To study the frequency of bacterial isolates of early onset neonatal sepsis (EONS) and their sensitivity pattern.
In this retrospective study, a case of EONS was defined as an infant who had clinical signs or born to mothers with potential risk factors for infection, in whom blood culture obtained within 72 hours of life, grew a bacterial pathogen. Blood culture sample included a single sample from peripheral vein or artery. Relevant data was obtained from the unit register or neonatal case records.
Of 2182 neonates screened, there were 389 (17.8%) positive blood cultures. After excluding coagulase-negative Staphylococci (160), we identified 229 EONS cases. Preterm neonates were 40.6% and small for gestational age, 18.3%. Mean birth weight and male to female ratio were 2344.5 (696.9) g and 1.16:1 respectively. Gram negative species represented 90.8% of culture isolates. Pseudomonas (33.2%) and Klebsiella (31.4%) were common among them. Other pathogens included Acinetobacter (14.4%), Staphylococcus aureus (9.2%), E.coli (4.4%), Enterobacter (2.2%), Citrobacter (3.1%) and Enterococci (2.2%). In Gram negative group, best susceptibility was to Amikacin (74.5%), followed by other aminoglycosides, ciprofloxacin and cefotaxime. The susceptibility was remarkably low to ampicillin (8.4%). Gram positive group had susceptibility of 42.9% to erythromycin, 47.6% to ciprofloxacin and above 50% to aminoglycosides. Of all isolates, 83.8% were susceptible to either cefotaxime or amikacin
Gram-negative species especially Pseudomonas and Klebsiella were the predominant causative organisms. Initial empirical choice of cefotaxime in combination with amikacin appeared to be rational choice for a given cohort.
PMCID: PMC3444145  PMID: 21745376
Early onset sepsis; neonates; blood culture isolates; antibiotic susceptibility
23.  Antiobiotic resistance pattern of biofilm-forming uropathogens isolated from catheterised patients in Pondicherry, India 
The Australasian Medical Journal  2012;5(7):344-348.
Microbial biofilms pose a public health problem for persons requiring indwelling medical devices, as micro-organisms in biofilms are difficult to treat with antimicrobial agents. Thus the present study includes biofilm formation and antibiotic resistance pattern of uropathogens in hospitalised patients with catheter associated urinary tract infections (UTI).
This prospective analysis included 100 urine samples from catheterised patients with symptoms of UTI over a period of six months. Following identification, all isolates were subjected to antibiotic sensitivity using modified Kirby- Bauer disc diffusion method. Detection of biofilms was done by tube adherence method and Congo red agar method.
E.coli was found to be the most frequently isolated uropathogen 70%, followed by Klebsiella pneumoniae 16%, Pseudomonas aeruginosa 4%, Acinetobacter spp 2%, coagulase negative Staphylococci 6% and Enterococci Spp 2%. In the current study 60% of strains were in vitro positive for biofilm production. Biofilm positive isolates showed 93.3%, 83.3%, 73.3% and 80% resistance to nalidixic acid, ampicillin, cephotaxime and cotrimoxazole, respectively, compared to 70%, 60%, 35%, 60% resistance showed by biofilm non-producers for the respective antibiotics. Approximately 80% of the biofilm producing strains showed multidrug resistant phenotype
To conclude E.coli was the most frequent isolate, of which 63% were biofilm producers. The antibiotic susceptibility pattern in the present study showed quinolones were the least active drug against uropathogens. The uropathogens showed the highest sensitivity to carbapenems. The next best alternatives were aminoglycosides. Significant correlation between biofilm production and multi-drug resistance was observed in our study.
PMCID: PMC3412999  PMID: 22905060
Biofilm; Uropathogens; Tube adherence method; Congo red agar method
24.  Multiplex Identification of Gram-Positive Bacteria and Resistance Determinants Directly from Positive Blood Culture Broths: Evaluation of an Automated Microarray-Based Nucleic Acid Test 
PLoS Medicine  2013;10(7):e1001478.
Nathan Ledeboer and colleagues assess the performance of a diagnostic platform for detecting Gram-positive bacteria in blood cultures, an important step in the diagnosis and treatment of patients with sepsis.
Please see later in the article for the Editors' Summary
A multicenter study was conducted to evaluate the diagnostic accuracy (sensitivity and specificity) of the Verigene Gram-Positive Blood Culture Test (BC-GP) test to identify 12 Gram-positive bacterial gene targets and three genetic resistance determinants directly from positive blood culture broths containing Gram-positive bacteria.
Methods and Findings
1,252 blood cultures containing Gram-positive bacteria were prospectively collected and tested at five clinical centers between April, 2011 and January, 2012. An additional 387 contrived blood cultures containing uncommon targets (e.g., Listeria spp., S. lugdunensis, vanB-positive Enterococci) were included to fully evaluate the performance of the BC-GP test. Sensitivity and specificity for the 12 specific genus or species targets identified by the BC-GP test ranged from 92.6%–100% and 95.4%–100%, respectively. Identification of the mecA gene in 599 cultures containing S. aureus or S. epidermidis was 98.6% sensitive and 94.3% specific compared to cefoxitin disk method. Identification of the vanA gene in 81 cultures containing Enterococcus faecium or E. faecalis was 100% sensitive and specific. Approximately 7.5% (87/1,157) of single-organism cultures contained Gram-positive bacteria not present on the BC-GP test panel. In 95 cultures containing multiple organisms the BC-GP test was in 71.6% (68/95) agreement with culture results. Retrospective analysis of 107 separate blood cultures demonstrated that identification of methicillin resistant S. aureus and vancomycin resistant Enterococcus spp. was completed an average of 41.8 to 42.4 h earlier using the BC-GP test compared to routine culture methods. The BC-GP test was unable to assign mecA to a specific organism in cultures containing more than one Staphylococcus isolate and does not identify common blood culture contaminants such as Micrococcus, Corynebacterium, and Bacillus.
The BC-GP test is a multiplex test capable of detecting most leading causes of Gram-positive bacterial blood stream infections as well as genetic markers of methicillin and vancomycin resistance directly from positive blood cultures.
Please see later in the article for the Editors' Summary
Editors' Summary
Severe sepsis—a life-threatening condition that is usually is triggered by a bacterial infection of the bloodstream—is a major global cause of illness and death. In the US alone, sepsis causes up to 500,000 hospital admissions and more than 250,000 deaths a year. Normally, when microbes enter the human body, the immune system efficiently kills the invaders. In sepsis, the immune system goes into overdrive and the chemicals it releases into the blood to combat the infection trigger widespread inflammation, which leads to the formation of small blood clots and leaky blood vessels that impair the flow of blood to vital organs. In the most severe cases, multiple organs fail and the patient dies. Anyone can get sepsis but people with weakened immune systems, the elderly, and the very young are most vulnerable. Symptoms of sepsis include fever, chills, rapid breathing, and a fast heart rate. In its early stages, sepsis can be treated with antibiotics alone, but people with severe sepsis need to be admitted to an intensive care unit where their vital organs can be supported while the infection is treated.
Why Was This Study Done?
The outcome of sepsis is affected by many factors, but fast, accurate identification of the bacterial infection and determination of its antibiotic susceptibility is essential to ensure that patients receive appropriate antibiotics. Laboratory diagnosis of bloodstream infections currently requires incubation of blood samples in a liquid medium (broth) followed by growth on solid media to identify the bacteria and to test for antibiotic sensitivity. It takes about 3 days after a positive broth culture is obtained to complete this process during which time patients are treated with broad spectrum antimicrobials, which may be ineffective. In this study, the researchers evaluate the sensitivity (a test's ability to identify patients who are positive for a specific condition) and specificity (a test's ability to identify patients who do not have a specific condition) of the Verigene BC-GP test. This multiplex, automated microarray-based nucleic acid test has been developed to directly and simultaneously identify 12 species of Gram-positive bacteria (the commonest cause of bacterial bloodstream infections) and three antibiotic resistance determinants in blood culture broths that contain Gram-positive bacteria.
What Did the Researchers Do and Find?
The researchers used the Verigene BC-GP test and reference culture methods to identify the bacterial species and antibiotic resistance determinants present in 1,252 blood cultures containing Gram-positive bacteria collected at five US clinical centers and in 387 contrived blood cultures that contained bacterial species rarely found in the bloodstream. Compared to the reference culture method, the sensitivity of the Verigene BC-GP test for the bacterial species included in the test ranged from 92.6% to 100%; its specificity was 94.5%–100%. Identification of the mecA gene (a genetic marker for methicillin resistance) in cultures that contained Staphylococcus aureus or S. epidermis (Gram-positive bacteria that are often methicillin resistant) was 98.6% sensitive and 94.3% specific. Identification of the vanA gene (a genetic marker for vancomycin resistance) was 100% sensitive and specific in cultures containing Enterococcus species. Only 7.5% of single-organism cultures contained Gram-positive bacteria not present in the Verigene BC-GP test panel. Importantly, results obtained with the new test agreed those obtained with reference culture methods in three-quarters of cultures that contained more than one bacterial species. Finally, in a retrospective analysis of turn-around-time, identification of methicillin-resistant S. aureus and vancomycin-resistant Enterococcus species with the Verigene BC-GP test was about 42 hours faster than with reference methods.
What Do These Findings Mean?
These findings show that the Verigene BC-GP test is capable of accurately identifying most leading causes of bloodstream infection with Gram-positive bacteria. Moreover, they show that the test can detect genetic markers of methicillin and vancomycin resistance directly from positive blood cultures, although they also reveal that the test cannot assign mecA positivity to a specific organism in a mixed culture, a finding that may mean that some patients are treated with unnecessary antibiotics. Overall, the researchers conclude that the Verigene BC-GP test has the potential to markedly reduce the turn-around-time for reporting bacterial identification from positive blood cultures. Its use should, therefore, improve the care of patients with sepsis by allowing physicians to prescribe appropriate antibiotics much earlier than is currently possible.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Institute of General Medical Sciences has a fact sheet on sepsis
The UK National Health Service Choices website has information about sepsis
The Sepsis Alliance, a US not-for-profit organization, provides information about sepsis for patients and their families, including personal stories about sepsis
The not-for profit UK Sepsis Trust is another useful source of information about sepsis that includes patient stories
Wikipedia has a page on Gram-positive bacteria (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Medlineplus provides links to additional resources about sepsis and about bacterial infections (in English and Spanish)
PMCID: PMC3699453  PMID: 23843749
25.  Antimicrobial susceptibility pattern of bacterial isolates from wound infection and their sensitivity to alternative topical agents at Jimma University Specialized Hospital, South-West Ethiopia 
Wound infection is one of the health problems that are caused and aggravated by the invasion of pathogenic organisms. Information on local pathogens and sensitivity to antimicrobial agents, and topical agents like acetic acid is crucial for successful treatment of wounds.
To determine antimicrobial susceptibility pattern of bacterial isolates from wound infection and their sensitivity to alternative topical agents at Jimma University Specialized Hospital.
A cross sectional study was conducted among patients with wound infection visiting Jimma University Specialized Hospital, from May to September 2013. Wound swab was collected using sterile cotton swabs and processed for bacterial isolation and susceptibility testing to antimicrobial agents, acetic acid, hydrogen peroxide and dabkin solution following standard bacteriological techniques. Biochemical tests were done to identify the species of the organisms. Sensitivity testing was done using Kirby- Baur disk diffusion method. Minimum inhibitory and bactericidal concentration was done using tube dilution method.
In this study 145 bacterial isolates were recovered from 150 specimens showing an isolation rate of 87.3%. The predominant bacteria isolated from the infected wounds were Staphylococcus aureus 47 (32.4%) followed by Escherichia coli 29 (20%), Proteus species 23 (16%), Coagulase negative Staphylococci 21 (14.5%), Klebsiella pneumoniae 14 (10%) and Pseudomonas aeruginosa 11 (8%). All isolates showed high frequency of resistance to ampicillin, penicillin, cephalothin and tetracycline. The overall multiple drug resistance patterns were found to be 85%. Acetic acid (0.5%), Dabkin solution (1%) and 3% hydrogen peroxide were bactericidal to all isolated bacteria and lethal effect observed when applied for 10 minutes.
On in vitro sensitivity testing, ampicillin, penicillin, cephalothin and tetracycline were the least effective. Gentamicin, norfloxacin, ciprofloxacin, vancomycin and amikacin were the most effective antibiotics. Acetic acid (0.5%), dabkin solution (1%) and H2O2 (3%) were bactericidal to all isolates.
PMCID: PMC4017222  PMID: 24731394
Bacterial pathogens; Drug resistance; Wound infection; Jimma; Ethiopia

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