Pharmacokinetic considerations in selecting optimal antibiotic therapy for Mycoplasma pneumoniae encephalitis.

Effective antimicrobial therapy depends on several factors including degree of activity against the pathogen, antibiotic resistance, and when relevant, optimal tissue penetration factors. Central nervous system (CNS) infections illustrate these points well. The pharmacokinetic (PK) parameters important in antibiotic blood cerebrospinal fluid barrier (BCB) penetration that is important in meningitis are different and do not predict blood brain barrier (BBB) penetration. Recently, we had a case of Mycoplasma pneumoniae encephalitis (MPE) which prompted a review of the antibiotic PK determinants of BBB penetration which differ markedly from those of BCB penetration important in encephalitis. Using MPE as an illustrative example, this article reviews host and drug factors of therapeutic importance in optimally treating MPE.

Case report of a 6-year-old girl with Mycoplasma hominis ventriculoperitoneal shunt infection.

Mycoplasma hominis is a rare causative pathogen for surgical site infections after neurosurgical procedures. This organism lacks a cell wall, rendering it undetectable by Gram staining and making it resistant to beta-lactam antibiotics. In addition, some special techniques are required to identify this organism. Thus, it is very difficult to diagnose infections caused by this pathogen. Here, the authors report a pediatric case of M. hominis ventriculoperitoneal shunt (VPS) infection with central nervous system involvement for which beta-lactam antibiotics were not effective and Gram staining revealed no pathogens. Because few cases have been described that involve the treatment of M. hominis infection after neurosurgery, in this case the patient's serum and CSF were monitored for antibiotic drug concentrations. Successful treatment of the infection was achieved after approximately 6 weeks of administration of clindamycin and ciprofloxacin antibiotics in addition to external ventricular drain revision and subsequent VPS replacement. When beta-lactam antibiotics are ineffective and when Gram staining cannot detect the responsible pathogens, it is important to consider M. hominis as the atypical pathogen.

Chronic meningitis with intracranial hypertension and bilateral neuroretinitis following Mycoplasma pneumoniae infection.

A previously well 12-year-old boy presented with a 2-week history of headache, nausea, vomiting and left-sided weakness. He subsequently developed meningism, right abducens nerve palsy, persistent papilloedema and reduced visual acuity in association with a bilateral macular star, consistent with neuroretinitis. Cerebrospinal fluid (CSF) examination indicated chronic meningitis and serological testing confirmed recent Mycoplasma pneumoniae infection, although PCR in CSF was negative. He was treated for aseptic meningitis with ceftriaxone, aciclovir, azithromycin and acetazolamide for intracranial hypertension, with gradual improvement in clinical condition and visual acuity over several weeks. This is the first report of M. pneumoniae chronic meningitis further complicated with bilateral neuroretinitis and intracranial hypertension. Evidence of central nervous system inflammation in the absence of direct infection suggests an immune-mediated pathophysiology. Although the use of macrolides with antibiotic and immunomodulatory activity might be beneficial, it was not possible to ascertain whether it influenced clinical recovery in this case.

Immediate relief of Mycoplasma pneumoniae encephalitis symptoms after intravenous immunoglobulin.

Mycoplasma pneumoniae may cause acute encephalitis, resulting in severe neurologic complications despite antibiotic therapy. We report the case of a 12-year-old patient who presented with acute onset of orofacial tics, motor restlessness, compulsive behavior, and cerebellar symptoms. Cerebrospinal fluid examination demonstrated lymphocytic meningitis. Polymerase chain reaction for M. pneumoniae was strongly positive in the cerebrospinal fluid. Blood and cerebrospinal fluid were negative for M. pneumoniae antibodies (immunoglobulin M and immunoglobulin G). The child was administered intravenous gamma-globulin, which led to a dramatic improvement of her clinical condition and disappearance of the symptoms within 72 hours. This novel case points to the potential value of gamma-globulin in M. pneumoniae encephalitis confirmed with polymerase chain reaction and suggests that immediate administration of intravenous gamma-globulin in suspected mycoplasma encephalitis should be investigated in a larger patient cohort.

Absence of Mycoplasma-specific DNA sequence in brain, blood and CSF of patients with multiple sclerosis (MS): a study by PCR and real-time PCR.

Mycoplasmas are the smallest of the known self-replicating organisms. They lack cell walls and are associated with numerous diseases in humans and animals. We are exploring the possibility that infection by Mycoplasma may induce the inflammatory demyelinating disease of the central nervous system (CNS) that is MS. The presence of specific Mycoplasma species DNA was sought in brain, serum and cerebrospinal fluid (CSF) of patients diagnosed with multiple sclerosis (MS) and other neurological diseases (OND) including inflammatory disorders. The MS samples from patients with active and progressive MS, as well as in remission, a variety of other neurological disease controls, including inflammatory CNS diseases such as meningitis, cryptococcal meningitis and encephalitis and other neurological disorders such as migraine were also examined. Clinical samples were provided by the National Neurological Research Specimen Bank and the Human Brain and Spinal Fluid Resource Centre, Los Angeles. Analysis was carried out by conventional PCR using Mycoplasma-specific primers (McAuliffe et al., 2005) that target the 16S rDNA gene in Mycoplasma species. The Mycoplasma-specific primers could detect 102 Mycoplasma species. In this study, 30 samples of human brain and 57 pairs of serum and CSF and were examined. No Mycoplasma-specific nucleic acid sequence was detected, and the consistent observation of an endogenous gene, human serum albumin (HSA), as a positive control documented the adequacy of the method. Real-time PCR analysis of serum and CSF was done also targeting utilizing the Mycoplasma 16S rDNA gene, and this also demonstrated the lack of Mycoplasma in these samples. The presence of Mycoplasma at extraneural sites in MS patients is now being explored.

[Infection due to Mycoplasma pneumoniae: three cases with neurological complications]. / Infección por Myoplasma Pneumoniae: tres casos con complicaciones neurológicas.

INTRODUCTION: Mycoplasma pneumoniae infection has been associated with severe central nervous system diseases. The pathogenesis of these disorders is unknown and the treatment uncertain. CASE REPORTS: The authors present three cases of central nervous system diseases: acute transverse myelitis, cerebellitis and encephalomyelitis associated with M. pneumoniae infection. CONCLUSIONS: M. pneumoniae infection should be considered in all cases of severe acute central nervous system symptomatology.

Detection of Mycoplasma pneumoniae from cerebrospinal fluid samples of pediatric patients.

Central nervous system manifestations are probably the most frequent extrapulmonary complications of infections due to Mycoplasma pneumoniae, occur mostly in children. In this study, we attempted to isolate M. pneumoniae and to detect the organism by polymerase chain reaction (PCR) from cerebrospinal fluid samples (CSF) of pediatric patients. Of the 244 CSF samples, no M. pneumoniae was isolated. Six (2.5%) of the CSF samples were positive by PCR amplification. More effort are necessary to isolate the organism from CSF samples in order to ascertain the role of M. pneumoniae in causing neurological complications.

Isolation pattern and clinical outcome of genital mycoplasma in neonates from a tertiary care neonatal unit.

The role of genital mycoplasma in perinatal mortality and morbidity has been debated. This study was undertaken to determine the frequency of isolation of genital mycoplasma and evaluate its association with clinical outcome. Sixty-six cerebrospinal fluid (CSF) and 49 tracheal aspirates taken from 100 low birthweight infants who had suspected meningitis and/or respiratory distress respectively were cultured for genital mycoplasma. Ureaplasma urealyticum was isolated from 9 per cent of CSF and 14 per cent of tracheal aspirates. Mycoplasma hominis was isolated from CSF in one case and none at the tracheal aspirates. Three out of seven mycoplasma-infected CNS cases showed CSF pleocytosis while three out of seven patients whose tracheal aspirates grew mycoplasma had congenital pneumonia. None of the patients were treated with antimycoplasmal therapy and none developed chronic lung disease.

Cerebrospinal fluid concentrations of interleukin-1 beta, tumour necrosis factor-alpha, and interferon gamma in bacterial meningitis.

To investigate the role of the inflammatory cytokines, the cerebrospinal fluid concentrations of interleukin (IL)-1 beta, tumour necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were measured in 11 children with bacterial meningitis and two with mycoplasmic meningoencephalitis and compared with those in 50 children with aseptic meningitis and 15 with non-pleocytotic cerebrospinal fluid. Concentrations of IL-1 beta and TNF-alpha were each significantly higher in the cerebrospinal fluid of patients with bacterial meningitis than in those with aseptic meningitis or those with non-pleocytotic cerebrospinal fluid. IFN-gamma was detected at low concentrations in the cerebrospinal fluid of only 2/11 of those with bacterial meningitis. On the other hand, the IFN-gamma concentration was the highest in the cerebrospinal fluid of patients with aseptic meningitis. These results suggest that the inflammatory cytokines are differently released in the intrathecal space infected with viruses or bacteria.

Mycoplasma hominis and Ureaplasma urealyticum in neonates with suspected infection.

The role of genital mycoplasmas in the pathogenesis of neonatal infection is incompletely understood. We performed nasopharyngeal, blood and cerebrospinal fluid (CSF) cultures for Mycoplasma hominis and Ureaplasma urealyticum in 69 neonates who underwent a diagnostic workup for suspected sepsis. The mean gestational age was 35.9 weeks (range, 25 to 42 weeks) with a mean birth weight of 2386 g (range, 652 to 4420 g). Twenty-seven infants (39.1%) had positive nasopharyngeal cultures; 6 were positive for M. hominis, 10 for U. urealyticum and 11 for both organisms. Seven (26%) of these 27 patients developed chronic lung disease compared with 2 (4.7%) infants in the non-colonized group. Nine infants had positive CSF cultures for M. hominis and one infant had a positive CSF culture for U. urealyticum. All blood cultures were sterile. One of the infants with a positive CSF culture for M. hominis had clinical evidence of systemic infection. All of the infants were treated with antibiotic agents that were not active against mycoplasmas. These data indicate that genital mycoplasmas can be found commonly in the CSF and nasopharynx of infants with suspected sepsis. Their etiologic role in the causation of infection and chronic lung disease, however, remains unclear.

DNA diagnosis of central nervous system infection by Mycoplasma pneumoniae.

A nested polymerase chain reaction method for the detection of Mycoplasma pneumoniae was devised and applied to clinical samples. This system could detect 5 to 50 fg of the DNA from M pneumoniae and did not amplify the DNA from Mycoplasma genitalium. With this method, the sequence of this organism was detected successfully in cerebrospinal fluid samples from four of six patients and in serum samples from three of four patients with clinically and serologically confirmed mycoplasmal central nervous system infection. This strongly suggested the direct invasion of this organism into the central nervous system and the concomitant occurrence of mycoplasmaremia. The nested amplification method is considered to be simple, rapid, and sensitive without the use of radioisotopes, thereby being highly applicable as a useful tool in routine clinical laboratories for the preliminary detection and diagnosis of mycoplasmal infections, particularly in extrapulmonary cases.

Mycoplasmal infections of cerebrospinal fluid in newborn infants from a community hospital population.

Mycoplasma hominis or Ureaplasma urealyticum have previously been isolated from cerebrospinal fluid (CSF) in 13 of 100 newborn infants tested from a high risk university hospital population where the mothers were of predominantly lower income and socioeconomic status and had often received little or no prenatal care. We sought to determine whether such infections occur in neonates born to women cared for mainly through private obstetric practices and who delivered in 4 suburban community hospitals. CSF cultures were done in 318 infants during an 8-month period. M. hominis was isolated from 9 and U. urealyticum from 5 CSF cultures. Four infants infected with U. urealyticum and 3 infected with M. hominis were born at term. One infant infected with U. urealyticum had a birth weight of less than 1000 g. In 5 infants clearance of the infecting organism was documented without specific treatment. Twelve infants had good perinatal outcomes regardless of treatment and 2 died. One death in a 2240-g infant infected with M. hominis was associated with Haemophilus influenzae sepsis and pneumonia. The other death occurred 3 days after birth in a 630-g infant infected with U. urealyticum who had evidence of meningitis and intraventricular hemorrhage. Results of this study suggest that mycoplasmas are common causes of neonatal CSF infections, not only in high risk populations, but also in the general population.