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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.