Cerebrospinal Pharmacokinetic Analysis and Pharmacodynamic Evaluation of Ceftriaxone in Pediatric Patients with Bacterial Meningitis

<div>Cerebrospinal pharmacokinetic model of ceftriaxone. <svg height="11.927pt" id="M5" style="vertical-align:-3.291101pt" version="1.1" viewbox="-0.0498162 -8.6359 14.2689 11.927" width="14.2689pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M748 650H522L515 622L546 617C580 611 587 604 565 575C518 513 469 451 419 393C376 474 349 534 330 580C318 609 325 612 361 618L383 622L392 650H151L144 622C214 616 224 612 257 543L360 327C270 218 187 124 159 95C106 40 92 34 26 28L17 0H252L259 28L236 31C189 37 188 47 209 78C249 136 308 210 377 294L478 79C494 44 487 37 449 32L418 28L409 0H673L680 28C596 34 591 39 554 116L436 361C526 469 574 521 604 553C659 612 669 614 739 622L748 650Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,9.88,3.132)"><path d="M387 400C387 425 348 451 303 451C247 451 176 414 132 376C69 322 24 228 24 148C24 43 74 -12 147 -12C211 -12 301 33 363 103L346 128C319 99 249 51 193 51C148 51 112 84 112 165C112 230 130 287 154 330C170 359 199 400 243 400C277 400 304 383 326 354C333 345 343 343 354 348C378 360 387 382 387 400Z"></path></g></svg> and <svg height="11.9453pt" id="M6" style="vertical-align:-3.309401pt" version="1.1" viewbox="-0.0498162 -8.6359 25.6409 11.9453" width="25.6409pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M748 650H522L515 622L546 617C580 611 587 604 565 575C518 513 469 451 419 393C376 474 349 534 330 580C318 609 325 612 361 618L383 622L392 650H151L144 622C214 616 224 612 257 543L360 327C270 218 187 124 159 95C106 40 92 34 26 28L17 0H252L259 28L236 31C189 37 188 47 209 78C249 136 308 210 377 294L478 79C494 44 487 37 449 32L418 28L409 0H673L680 28C596 34 591 39 554 116L436 361C526 469 574 521 604 553C659 612 669 614 739 622L748 650Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,9.88,3.132)"><path d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,15.932,3.132)"><path d="M409 504C401 567 396 607 392 642C354 654 312 665 266 665C137 665 60 583 60 487C60 374 161 325 225 290C300 250 355 215 355 141C355 68 311 21 235 21C131 21 86 122 71 183L41 176C48 128 61 42 68 21C78 16 93 8 118 0C142 -7 175 -15 216 -15C349 -15 438 69 438 174C438 287 344 333 265 374C186 414 138 449 138 522C138 576 172 631 249 631C336 631 363 562 380 499L409 504Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,20.135,3.132)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"></path></g></svg> are the amounts of ceftriaxone (mg) in the central and cerebrospinal fluid (CSF) compartments; CL, clearances (<i>L</i>/<i>h</i>/kg); <svg height="11.9087pt" id="M7" style="vertical-align:-3.2728pt" version="1.1" viewbox="-0.0498162 -8.6359 33.1125 11.9087" width="33.1125pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M697 650H468L461 623L492 619C539 613 547 605 518 546C481 471 367 264 278 116H276C239 278 197 500 186 567C180 604 185 613 226 619L252 623L260 650H24L17 623C78 617 92 613 108 533L216 -11H247C365 200 515 462 560 529C616 612 624 615 689 623L697 650Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.332,3.132)"><path d="M390 111C344 68 312 56 269 56C212 56 118 102 118 241C118 346 175 401 241 401C277 401 312 388 342 360C350 352 355 349 361 349C372 349 394 371 394 392C394 403 391 411 378 422C362 436 329 449 288 449H287C250 449 190 432 138 392C71 341 37 274 37 197C37 90 112 -12 238 -12C297 -12 363 32 407 90L390 111Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,11.181,3.132)"><path d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,15.049,3.132)"><path d="M524 0V26C466 32 460 36 460 104V297C460 393 411 449 331 449C302 449 276 437 248 419C223 402 201 387 181 372V451C137 432 90 420 42 411V388C96 378 102 374 102 310V104C102 38 97 33 29 26V0H246V26C187 32 181 36 181 104V339C211 365 250 390 290 390C357 390 381 345 381 276V109C381 40 374 32 315 26V0H524Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,19.853,3.132)"><path d="M298 36L289 62C276 55 253 45 228 45C202 45 169 60 169 141V397H276C289 405 292 426 282 437H169V574L155 576L90 509V437H45L17 408L21 397H90V107C90 28 125 -12 188 -12C198 -12 213 -8 230 1L298 36Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,22.674,3.132)"><path d="M181 342V451C133 431 89 419 40 411V388C98 381 102 377 102 311V104C102 38 95 32 33 26V0H263V26C186 32 181 38 181 104V287C203 343 235 372 261 372C277 372 289 366 304 352C310 346 318 345 330 350C349 359 362 379 362 399C362 422 338 449 304 449C256 449 213 393 183 342H181Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,26.05,3.132)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,30.091,3.132)"><path d="M238 0V26C174 32 166 38 166 104V712C132 700 70 683 18 677V653C81 647 87 645 87 577V104C87 38 78 32 15 26V0H238Z"></path></g></svg> and <span class="nowrap"><svg height="11.9453pt" id="M8" style="vertical-align:-3.309401pt" version="1.1" viewbox="-0.0498162 -8.6359 23.0833 11.9453" width="23.0833pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M697 650H468L461 623L492 619C539 613 547 605 518 546C481 471 367 264 278 116H276C239 278 197 500 186 567C180 604 185 613 226 619L252 623L260 650H24L17 623C78 617 92 613 108 533L216 -11H247C365 200 515 462 560 529C616 612 624 615 689 623L697 650Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.332,3.132)"><path d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,13.384,3.132)"><path d="M409 504C401 567 396 607 392 642C354 654 312 665 266 665C137 665 60 583 60 487C60 374 161 325 225 290C300 250 355 215 355 141C355 68 311 21 235 21C131 21 86 122 71 183L41 176C48 128 61 42 68 21C78 16 93 8 118 0C142 -7 175 -15 216 -15C349 -15 438 69 438 174C438 287 344 333 265 374C186 414 138 449 138 522C138 576 172 631 249 631C336 631 363 562 380 499L409 504Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,17.587,3.132)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"></path></g></svg>,</span> distribution volumes of the central and CSF compartments (L/kg); <span class="nowrap"><svg height="11.9453pt" id="M9" style="vertical-align:-3.309401pt" version="1.1" viewbox="-0.0498162 -8.6359 25.0798 11.9453" width="25.0798pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M699 368C699 549 574 666 407 666C186 666 23 488 23 277C23 113 129 -3 288 -13L307 -26C431 -111 501 -139 533 -147C559 -154 613 -163 658 -164L666 -141C597 -111 507 -66 430 -11L416 -1C580 42 699 190 699 368ZM601 371C601 227 518 54 381 22L354 40L278 24C175 47 120 145 120 269C120 451 235 631 398 631C540 631 601 521 601 371Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,9.321,3.132)"><path d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,15.372,3.132)"><path d="M409 504C401 567 396 607 392 642C354 654 312 665 266 665C137 665 60 583 60 487C60 374 161 325 225 290C300 250 355 215 355 141C355 68 311 21 235 21C131 21 86 122 71 183L41 176C48 128 61 42 68 21C78 16 93 8 118 0C142 -7 175 -15 216 -15C349 -15 438 69 438 174C438 287 344 333 265 374C186 414 138 449 138 522C138 576 172 631 249 631C336 631 363 562 380 499L409 504Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,19.576,3.132)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"></path></g></svg>,</span> CSF flow clearance; KP<sub>CSF</sub>, CSF to serum partition coefficient.</div>

Journal of Clinical Pharmacy and Therapeutics

fig1

Figure 1

Figure 1: Cerebrospinal Pharmacokinetic Analysis and Pharmacodynamic Evaluation of Ceftriaxone in Pediatric Patients with Bacterial Meningitis 