The treatment of neonatal meningitis due to Gram-negative bacilli with ciprofloxacin: Evidence of satisfactory penetration into the cerebrospinal fluid

doi:10.1016/0163-4453(93)95291-P

Journal of Infection

Volume 26, Issue 3, May 1993, Pages 253-256

https://doi.org/10.1016/0163-4453(93)95291-P Get rights and content

Summary

We describe two cases of neonatal meningitis due to Gram-negative bacilli treated successfully with ciprofloxacin. Examination of serial samples of cerebrospinal fluid indicated the effect of meningeal inflammation on penetration of this drug into the CSF.

References (7)

De LouvoisJ et al.
Infantile meningitis in England and Wales: a two year study
Arch Dis Child
(1991)
McClainJB et al.
Cerebrospinal fluid concentrations of ciprofloxacin in subjects with uninflamed meninges
J Antimicrob Chemother
(1988)
WolffM et al.
Penetration of ciprofloxacin into cerebrospinal fluid of patients with bacterial meningitis
Antimicrob Agents Chemother
(1987)

There are more references available in the full text version of this article.

Cited by (44)

Combination therapy with ciprofloxacin and third-generation cephalosporin versus third-generation cephalosporin monotherapy in Escherichia coli meningitis in infants: a multicentre propensity score–matched observational study
2019, Clinical Microbiology and Infection
Citation Excerpt :
Ciprofloxacin has bactericidal activity on Gram-negative rods, with low MIC for E. coli (modal MIC = 0.016 mg/L) (http://mic.eucast.org/). Furthermore, it has good tissue, intracellular and CSF penetration [6,9,13,14]. Indeed, intracellular ciprofloxacin levels are 4 to 5 times higher than serum levels, and CSF ciprofloxacin levels in inflamed meninges reach concentrations far above MIC values for E. coli [14–16].
Escherichia coli is the second cause of bacterial meningitis in neonates. Despite the use for 35 years of third-generation cephalosporins (3GCs), high morbidity and mortality rates with E. coli meningitis continue to occur. Because ciprofloxacin has good microbiologic activity against E. coli and good penetration in cerebrospinal fluid and brain, some authors have suggested adding ciprofloxacin to a 3GC regimen. The objective of this study was to assess combining 3GCs with ciprofloxacin versus 3GCs alone in a cohort of infants with E. coli meningitis.
We included all cases of E. coli meningitis diagnosed in infants <12 months of age that were prospectively collected through the French paediatric meningitis surveillance network between 2001 and 2016. The main outcome was the proportion of short-term neurologic complications with versus without ciprofloxacin. The analysis was conducted retrospectively by multivariable regression and propensity score (PS) analysis.
Among the 367 infants enrolled, 201 (54.8%) of 367 had ciprofloxacin and 3GC cotreatment and 166 (45.2%) of 367 only a 3GC. Median age and weight were 15 days (range, 1–318 days) and 3.42 kg (range, 0.66–9.4 kg). A total of 86 (23.4%) of 367 infants presented neurologic complications (seizures, strokes, empyema, abscesses, hydrocephalus, arachnoiditis); 57 received ciprofloxacin cotreatment. Complications were associated with ciprofloxacin cotreatment on multivariable analysis (odds ratio (OR) = 1.9; 95% confidence interval (CI), 1.1–3.4) and PS analysis (OR = 1.9; 95% CI, 1.1–3.3). Mortality rate did not differ with and without ciprofloxacin: 22 (10.9%) of 201 versus 16 (9.6%) of 166 deaths (OR = 0.7; 95% CI, 0.3–1.6; PS analysis).
Ciprofloxacin added to 3GCs at least offers no advantage for neurologic outcome and mortality in infants with E. coli meningitis.
Appropriate use of fluoroquinolones in children
2015, International Journal of Antimicrobial Agents
Citation Excerpt :
FQs penetrate the cerebrospinal fluid (CSF) well in the presence of inflamed meninges, reaching concentrations that, despite varying from drug to drug, are generally sufficiently high to eradicate the infectious pathogen. In comparison with those measured in the serum, CSF concentrations are ca. 70% for LFX and 30% for CIP [33–38]. Several cases of successful treatment of meningitis due to Gram-negative rods in neonates have been reported [37–41].
With the increasing resistance to antibiotics among common bacterial pathogens, challenges associated with the use of fluoroquinolones (FQs) in paediatrics have emerged. The majority of FQs have favourable pharmacokinetic properties, although these properties can differ in children compared with adults. Moreover, all FQs have broad antimicrobial activity both against Gram-positive and Gram-negative bacteria. However, only some FQs for which adequate studies are available have been approved for use in children in a limited number of clinical situations owing to the supposed risk of development of severe musculoskeletal disorders, as demonstrated in juvenile animals. Recent short- and long-term evaluations appear to indicate that, at least for levofloxacin, this risk, if present at all, is marginal. This marginal risk could lead to more frequent use of FQs in children, even to treat diseases for which several other drugs with documented efficacy, safety and tolerability are considered the first-line antibiotics. However, for most of the FQs, adequate long-term studies of safety are not available. This indicates that the use of FQs should be limited to selected respiratory infections (including tuberculosis), exacerbation of lung disease in cystic fibrosis, central nervous system infections, enteric infections, febrile neutropenia, as well as serious infections attributable to FQ-susceptible pathogen(s) in children with life-threatening allergies to alternative agents. When considering diseases that could benefit from the use of FQs, particular attention must be paid to the choice of drug and its dosage, considering that not all of the FQs have been evaluated in different diseases.
Multiple brain abscesses complicating enterobacter cloacae sepsis in a premature infant
2010, Archives de Pediatrie
Une septicémie nosocomiale à Enterobacter cloacae est survenue au 21^e jour de vie chez un grand prématuré. Cinq abcès cérébraux sont apparus au 6^e jour d’une antibiothérapie adaptée (céfotaxime et aminoside) motivant l’association de céfépime et de ciprofloxacine pendant 4 semaines pour la céphalosporine et jusqu’à disparition des images neuroradiologiques pour la fluoroquinolone. L’évolution neurologique était normale à l’âge de 13 mois. Les indications et la tolérance de la ciprofloxacine en période néonatale sont discutées.
A neonatal infection with Enterobacter cloacae was diagnosed at day 21 in a premature infant. Five cerebral abscesses were discovered 6 days while a treatment with cefotaxim and amikacin was administered. We switched for axepim during 4 weeks and ciprofloxacin until complete regression of cerebral abscesses. At 13 months of age, the infant neurodevelopmental outcome was normal. Ciprofloxacin indications and tolerance during neonatal period are discussed.
Substituted 2,5-diazabicyclo[4.1.0]heptanes and their application as general piperazine surrogates: synthesis and biological activity of a Ciprofloxacin analogue
2010, Tetrahedron
Citation Excerpt :
Since a racemic cyclopropanation strategy was used in the synthesis of the 2,5-diazabicyclo[4.1.0]heptane core, the product 17 is racemic. It has been demonstrated previously that enantiomeric quinolones possessing a chiral heterocycle at position-7 show differences in activity, particularly when the chiral centre occurs alpha to a heteroatom.34 It is therefore possible that the reduced antibacterial activity of racemic 17 compared to the parent Ciprofloxacin may be the result of differences in activity between the enantiomeric forms of 17.
Piperazines and modified piperazines, such as homopiperazines and 2-methylpiperazines, are found in a wide range of pharmaceutical substances and biologically active molecules. In this study 2,5-diazabicyclo[4.1.0]heptanes, in which a cyclopropane ring is fused onto a piperazine ring, are described as modified piperazine analogues. Differentially N,N′-disubstituted and N-monosubstituted compounds can be readily prepared from 2-ketopiperazine in a few steps, using a Simmons–Smith reaction of 1,2,3,4-tetrahydropyrazines with diethylzinc and diiodomethane for the key cyclopropane ring formation. An analogue of the fluoroquinolone antibacterial Ciprofloxacin was synthesized using a palladium-catalyzed Buchwald–Hartwig cross-coupling to attach the diazabicyclo[4.1.0]heptane core to the 7-position of the fluoroquinolone core. The resultant analogue was demonstrated to have similar antibacterial activity to the parent drug Ciprofloxacin. X-ray crystallographic analysis of this analogue reveals a distorted piperazine ring in the diazabicyclo[4.1.0]heptane core. The pK_a of the conjugate acid of N-Cbz-monoprotected 2,5-diazabicyclo[4.1.0]heptane was determined to be 6.74±0.05, which is 1.3 pK_a units lower than the corresponding N-Cbz-monoprotected piperazine compound. The lower basicity of diazabicyclo[4.1.0]heptanes is due to the electron-withdrawing character of the adjacent cyclopropane rings. The modified physicochemical and structural properties of diazabicyclo[4.1.0]heptanes relative to piperazines are expected to lead to interesting changes in the pharmacokinetic and biological activity profile of these molecules.
Clinical Pharmacology of Antibacterial Agents
2006, Infectious Diseases of the Fetus and Newborn Infant
Clinical Pharmacology of Antibacterial Agents
2005, Infectious Diseases of the Fetus and the Newborn Infant

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Original articleThe treatment of neonatal meningitis due to Gram-negative bacilli with ciprofloxacin: Evidence of satisfactory penetration into the cerebrospinal fluid

Summary

Infantile meningitis in England and Wales: a two year study

Arch Dis Child

Cerebrospinal fluid concentrations of ciprofloxacin in subjects with uninflamed meninges

J Antimicrob Chemother

Penetration of ciprofloxacin into cerebrospinal fluid of patients with bacterial meningitis

Antimicrob Agents Chemother

Original article
The treatment of neonatal meningitis due to Gram-negative bacilli with ciprofloxacin: Evidence of satisfactory penetration into the cerebrospinal fluid