this study was conducted in tugela ferry , south africa , where tb incidence is 1,100 cases/100,000 population and > 80% of tb
mdr tb and xdr tb incidence was 118 cases and 72 cases/100,000 population , respectively , in 2007 ( 4 ) .
ethical approval for this study was obtained from albert einstein college of medicine , yale university , university of kwazulu - natal , and the kwazulu - natal department of health .
we performed a prospective cross - sectional study actively identifying patients with suspected tb in medical and tb wards , the hiv clinic , and the outpatient department at the tugela ferry district hospital during february 2008april 2009 .
a person with suspected tb was defined as someone having a self - reported cough of any duration or > 2 other signs or symptoms , including fever , night sweats , weight loss , or shortness of breath for any duration .
patients could be either newly manifesting tb symptoms or have been receiving tb treatment for > 2 months but currently reporting active tb symptoms ( i.e. , treatment failures ) .
sputum for this study was tested by microscopic analysis of auramine- and ziehl - nielsen  stained smears and middlebrook 7h11 agar and mycobacterial growth indicator tube 960 broth culture .
dst of positive cultures was performed by using the 1% proportional method on middlebrook 7h11 agar for isoniazid ( critical concentrations : isoniazid 0.2 g / ml , rifampin 1.0 g / ml , ethambutol 7.5 g / ml , streptomycin 2.0 g / ml , ofloxacin 2 g / ml , kanamycin 5.0 g / ml , capreomycin 10 g / ml , and ethionamide 5.0 g / ml ) .
dst was repeated on all drug - resistant isolates to confirm the observed resistance pattern .
the proportion of patients with xdr tb and drug - susceptibility patterns were described by using simple frequencies .
xdr tb treatment outcomes were reported as of november 2009 ; standard international definitions were used ( 11 ) .
of 912 enrolled patients with suspected tb , 209 ( 23% ) had culture - positive tb ( figure 2 ) .
of these patients , 30 ( 14% ) had mdr tb , of which 19 ( 63% of those with mdr tb ; 9% with culture - positive results ) had xdr tb .
determination of prevalence of tuberculosis ( tb ) and drug resistance among persons with suspected tb , tugela ferry , south afica , 20082009 .
dst , drug susceptibility testing ; mdr tb , multidrug - resistant tb ; xdr tb , extensively drug - resistant tb . among xdr
tb isolates , all 19 ( 100% ) were resistant to all 6 drugs routinely tested in kwazulu - natal province ( isoniazid , rifampin , ethambutol , streptomycin , ofloxacin , and kanamycin ) , which extended the trend seen in previous years toward increasing drug resistance ( figure 1 ) . of these isolates , 4 ( 21% )
were also resistant to capreomycin , and 13 ( 68% ) were resistant to capreomycin and ethionamide ( table 1 ) .
thus , an 8-drug resistance pattern was the predominant dst type among xdr tb patients in this cohort . * xdr tb , extensively drug - resistant tuberculosis ; inh , isoniazid ; rif , rifampin ; emb , ethambutol ; sm , streptomycin ; ofl , ofloxacin ; km , kanamycin ; cap , capreomycin ; eto , ethionamide . of 13 patients with 8-drug resistance xdr tb , 5 ( 38% ) were women ( median age 33.5 years , range 2451 years ) ( table 2 ) .
although 5 ( 38% ) had previously received ( or currently showed failure to ) first - line tb treatment , none had ever received treatment with second - line drugs for mdr tb .
twelve ( 92% ) patients were hiv infected ( median cd4 cell count 183.5 cells / mm , range 22670 cells / mm ) ; only 2 ( 17% ) were receiving antiretroviral therapy at the time of tb screening . *
mdr tb , multidrug - resistant tuberculosis ; xdr tb , extensively drug - resistant tb .
6-drug resistance , resistance to isoniazid , rifampin , ethambutol , ofloxacin , kanamycin , and streptomycin ; 7-drug resistance , resistance to isoniazid , rifampin , ethambutol , ofloxacin , kanamycin , streptomycin , and capreomycin ; 8-drug resistance , resistance to isoniazid , rifampin , ethambutol , ofloxacin , kanamycin , streptomycin , capreomycin , and ethionamide . 
first - line drugs used for treatment of persons with new tb cases or confirmed drug - susceptible tb include isoniazid , rifampin , ethambutol , and pyrazinamide . 
second - line drugs used for treatment of persons with confirmed mdr tb include ofloxacin , kanaymycin , ethionamide , p - aminosalicylic acid , and cycloserine or terizidone . among 13 xdr tb patients with 8-drug resistance , 7 ( 54% ) died ( median time to death 59 days , range 16205 days ) .
two patients were lost to follow - up , and 4 ( 31% ) are still living and receiving xdr tb treatment ( range 190502 days of follow - up ) . no trend in survival of patients with xdr tb was observed by drug - resistance pattern ( 6-drug vs 7-drug vs. 8-drug ) .
routine drug - resistance surveillance to first- and second - line drugs is conducted in tugela ferry , which has a high incidence of tb and hiv co - infection . in this study
, we expanded second - line testing for 2 additional bactericidal drugs ( capreomycin and ethionamide ) for treatment of patients with xdr tb .
resistance to 8 first - line and second - line drugs is the predominant pattern for xdr tb in tugela ferry , thereby severely limiting effective therapeutic options with available medications .
according to the standard xdr tb regimen used in this province , patients were receiving <3 active drugs ( pyrazinamide , p - aminosalicylic acid , and cycloserine ) , which increases the risk for treatment failure and further amplification of drug resistance .
these findings underscore the need for routine surveillance for resistance to all first - line and second - line drugs used and for tailoring regimens accordingly to improve treatment success and reduce emergence of more drug - resistant xdr tb strains .
first , the reliability of second - line dst is variable , and only recently have methods and critical concentrations been standardized ( 12 ) .
however , all drug - resistant isolates in this study had dst repeated to confirm observed results .
second , dst for other first - line drugs , such as pyrazinamide , and other second - line drugs was not conducted , although these drugs are often used for xdr tb treatment .
thus , the degree of drug resistance was likely to be only a minimum estimate .
third , although the proportion of xdr tb cases in this survey was high , the absolute number of xdr tb cases was low .
this small sample size limits our ability to make conclusions about treatment outcomes for patients with increasing drug - resistant isolates . however , previous studies from our site have shown poorer survival rates with increasing drug resistance ( 4 ) . expanded dst for second - line and third - line drugs is critical for xdr tb patient care . given
continued high and rapid number of deaths from xdr tb , better and more rapid methods for second - line dst are urgently needed to improve diagnosis and guide treatment .
although new drugs are being developed , efforts must target prevention of xdr tb and its transmission , earlier identification of cases , support of treatment completion for tb and mdr tb , and greater use of antiretroviral therapy for patients who are co - infected with hiv .
 we expanded second - line tuberculosis ( tb ) drug susceptibility testing for extensively drug - resistant mycobacterium tuberculosis isolates from south africa . 
 of 19 patients with extensively drug - resistant tb identified during february 2008april 2009 , 13 ( 68% ) had isolates resistant to all 8 drugs tested . 
 this resistance leaves no effective treatment with available drugs in south africa . 