**4. Etiology**

and suitable for the procedure. If *Listeria monocytogenes* grows in CSF or is suspected as the causative organism from the Gram smear, it is advisable to add ampicillin to vancomycin + gentamicin combination, because CSF concentrations of vancomycin are not bactericidal for Listeria.

Neonatal meningitis continues to retain its importance all over the world as an infectious disease because of its morbidity. Medical facilities that enable physicians to keep more and more premature infants alive in economically developed countries and, on the contrary side, limitations in access to healthcare systems in economically developing countries keep neonatal meningitis on the medical agenda in an era of highly developed antimicrobial management and immunization.

The incidence of meningitis in newborn period is so high that is incomparable to any other period in human life. Accurate determinations of incidence may not be possible due to lack of reporting by healthcare personnel and difficulties encountered by patients in access to healthcare institutions in economically underdeveloped countries. Nevertheless, it is estimated that 40,000–900,000 new cases of neonatal meningitis occur annually in these countries [1]. The incidence of neonatal meningitis, which is thought to be roughly one in 1000 live births, was reported to be 0.8–6.1 in 1000 live births in an article in which the results of 32 studies, carried

A great progress has been made in this field of infectious diseases, at least in economically developed countries, with the decline of mortality rate from 50% of the past 40 years to that of 10–15% of today; however, almost no change has occurred in neonatal meningitis in terms of mortality in economically developing countries and morbidity worldwide [3]. The case fatality rate varies between 13 and 59% with respect to country of origin. Neurological sequelae, primarily hearing loss, continue to be an important problem with rates of 20–58% in the neo-

Turkey, once an economically developing country, where meningitis constitutes less than 1% of the reported causes of infant mortality, sets a good example of how natural health indices are affected favorably by slight increases in national income. According to the World Bank data, as of 2015, neonatal mortality rate in Turkey is seven per 1000 live births [an 80% decline from the rate (33) in 1990] [5, 6]. Yapıcıoğlu and colleagues reported the meningitis incidence as 1.4% among healthcare-associated infections in their university hospital's neonatal unit in Turkey [7].

Major risk factors of neonatal meningitis are low birth weight (<2500 g), premature birth (before 37th week of gestation), premature rupture of membranes (before the onset of labor

**1. Introduction**

86 Selected Topics in Neonatal Care

**2. Epidemiology**

**3. Risk factors**

out after 1990, have been reviewed [2].

nates who manage to survive this relentless disease [1, 4].

In economically developed countries, owing to implementation of intrapartum antibiotic prophylaxis beginning in the second half of 1990s, the incidence of early-onset group B streptococcus infections declined, whereas that of late-onset group B streptococcus infections remained the same [8]. Group B streptococci (GBS) and *Escherichia coli* are responsible for about half and a quarter of neonatal bacterial meningitis cases, respectively. These agents are succeeded in order of frequency by *Listeria monocytogenes* or Gram-negative bacteria other than *E. coli* in some texts, *Streptococcus pneumoniae*, group a streptococci, and nontypable *Haemophilus influenzae*. Gram-positive organisms other than GBS are encountered as pathogens more often in very-low-birth-weight (<1500 g) infants. Although rarely, *Neisseria meningitidis* may cause meningitis in newborns [3, 9].

Despite the data from economically developed countries, GBS predominance in neonatal meningitis has been observed to be replaced by Gram-negative bacteria in economically underdeveloped countries. *Klebsiella pneumoniae* is the most common Gram-negative bacillus and is followed in frequency by *E. coli*.

The most likely causative pathogens in the first three days of life are GBS, *E. coli*, other enteric bacilli, and *L. monocytogenes*. In addition to these, other Gram-negative organisms, such as *Serratia marcescens, Pseudomonas aeruginosa*, and *Citrobacter koseri*, should also be listed as likely pathogens in neonates of four days of age and older. In neonates who have left their first seven days in life behind, *Acinetobacter, Stenotrophomonas*, multidrug-resistant *Klebsiella*, and Gram-positive organisms that have not been mentioned above should be considered as causative agents [10].

Neonatal infections caused by herpes simplex virus (HSV) occur one in 3200–10,000 live births. These infections, which may manifest as neonatal meningitis, constitute 0.2% of neonatal hospitalizations and 0.6% of neonatal deaths in hospital in the United States of America [11].

Fungal meningitis occurs on the grounds of risk factors, such as prematurity, central venous catheter, congenital immunodeficiency, and long-term antibiotic therapy. The most common fungal cause of neonatal meningitis is *Candida albicans* [12].

Enteroviruses and *Enterobacter sakazakii*, which has been detected to contaminate infant formula, are emerging pathogens of neonatal meningitis [13, 14].
