cases of invasive meningococcal disease in minnesota residents are required to be reported to the minnesota department of health ( mdh ) . laboratories throughout the state routinely submit isolates from patients with this disease to the mdh public health laboratory , where they are serogrouped by slide agglutination ( difco , detroit , mi , usa ) . in 1995 , the mdh began routinely testing antimicrobial susceptibilities on meningococcal isolates and retrospectively conducted susceptibility testing on all available meningococcal isolates that had been submitted since 1993 . panels contained cation - adjusted mueller - hinton broth with 2%5% lysed horse blood ( pml microbiologicals , wilsonville , or , usa ) and were incubated at 35c in co2 for 2024 h. an etest ( ab biodisk , solna , sweden ) was also used for isolates that demonstrated resistance to further quantify degree of resistance . mic breakpoints have recently been established by the clinical and laboratory standards institute for n. meningitidis ( 14 ) . molecular subtyping of the sibling isolates was done by pulsed - field gel electrophoresis ( pfge ) as described previously ( 15 ) . the rpob genes from rifampin - resistant and rifampin - sensitive isolates ( table 1 ) were amplified by polymerase chain reaction and sequenced by using primers described previously ( 13 ) . dna and peptide sequences were analyzed with bionumerics ( applied maths , austin , tx , usa ) and vector nti suite ( informax , north bethesda , md , usa ) . * wt , wildtype . z54353 ) . accession numbers of isolate sequences submitted to genbank : mdh02 - 2342 ( ay746965 ) , mdh02 - 2271 ( ay746964 ) , mdh97 - 498 ( ay746963 ) , mdh02 - 2398 ( ay746966 ) , mdh02 - 2408 ( ay746967 ) . the first known case of rifampin - resistant invasive meningococcal disease in minnesota occurred in 1996 . he was hospitalized for 10 days , received antimicrobial drug therapy , and survived . by etest , his serogroup b n. meningitidis isolate had a rifampin mic 32 g / ml . this was a sporadic case with no apparent links to any other previous or subsequent cases . in 2002 , fever , vomiting , and irritability developed in a 2-month - old infant , followed 12 hours later by labored breathing and a generalized rash . she was taken to a clinic where she experienced cardiac arrest and underwent cardiopulmonary resuscitation . waterhouse - friderichsen syndrome was noted on autopsy , and n. meningitidis was isolated from a swab of brain tissue . three days after the death of the case - patient and 1 day after completing a 2-day course of rifampin , a fever and lethargy developed in the case - patient 's 6-year - old sister . blood cultures were obtained and she was hospitalized , given antimicrobial drug treatment ( ceftriaxone ) , and observed . household contacts , along with other close contacts of the 6-year - old girl , again received chemoprophylaxis . it was recommended that adults be treated with ciprofloxacin and children be treated with ceftriaxone because of concerns that 1 or both siblings could have had rifampin - resistant meningococcal infections . isolates from both siblings were identified as serogroup c. the pfge patterns were indistinguishable and had , in fact , the most common pfge pattern seen for that serogroup in minnesota . antimicrobial susceptibility testing showed that the isolate from the case - patient was susceptible to ceftriaxone , penicillin , chloramphenicol , ciprofloxacin , and rifampin . the mic for rifampin was 0.008 g / ml . the isolate from the 6-year - old patient was susceptible to the same drugs , except for rifampin , which had an mic > 1 g / ml by broth microdilution and an mic > 32 g / ml by etest . a comparison of the nucleotide sequence of the rpob gene of both sibling isolates showed they were identical except for a single nucleotide change . this change resulted in a substitution of serine for phenylalanine at amino acid position 548 . this substitution has previously been associated with rifampin resistance in n. meningitidis ( 12 ) . the pfge subtype of the isolate from the rifampin - resistant case in 1996 differed from that of the siblings ' isolates . sequencing of the rpob gene from this isolate showed an amino acid substitution of histidine for tyrosine at position 552 . this substitution has also been previously associated with rifampin resistance in n. meningitidis ( table 1 ; mdh97 - 498 ) ( 11,13 ) . susceptibility results on meningococcal isolates from 1993 to 2003 for other antimicrobial agents are shown in table 2 . using the newly established breakpoints , we observed that 92% ( 303/331 ) of the isolates were susceptible to penicillin , 100% ( 205/205 ) were susceptible to ceftriaxone , 100% ( 331/331 ) were susceptible to meropenem , 100% ( 205/205 ) were susceptible to ciprofloxacin , 100% ( 331/331 ) were susceptible to chloramphenicol , and 48% ( 158/331 ) were susceptible to trimethoprim - sulfamethoxazole . primary cases of rifampin - resistant meningococcal disease are rare . while more common , secondary cases with rifampin resistance can develop following chemoprophylaxis with rifampin . ceftriaxone must be given parenterally but is the recommended prophylactic agent for infected pregnant women . according to the 2003 american academy of pediatrics report of the committee on infectious diseases , ciprofloxacin may be used by persons > 15 years of age . while few instances of ciprofloxacin resistance have been reported , its widespread use may result in greater resistance in n. meningitidis ( as has occurred in related pathogens such as neisseria gonorrhoeae ) ( 16,17 ) . persons receiving chemoprophylaxis should be advised about the potential of meningococcal disease developing , even though they have taken antimicrobial agents as prescribed . if a close contact who has been treated with rifampin becomes ill with meningococcal disease , alternative antimicrobial agents should be used for prophylaxis until rifampin sensitivity of the secondary infection can be established . although rifampin - resistant meningococcal disease is still rare after 30 years of using rifampin for chemoprophylaxis and ciprofloxacin resistance has rarely been observed , susceptibilities to chemoprophylactic agents should be monitored to ensure that recommendations are sufficiently effective to minimize the occurrence of secondary cases .
rifampin - resistant meningococcal disease occurred in a child who had completed rifampin chemoprophylaxis for exposure to a sibling with meningococcemia . 
 susceptibility testing of 331 case isolates found only 1 other case of rifampin - resistant disease in minnesota , usa , during 11 years of statewide surveillance . 
 point mutations in the rna polymerase  subunit ( rpob ) gene were found in isolates from each rifampin - resistant case - patient .